bluuebunny/crossref_metadata_2025 huggingface dataset:
Living “light green”: the limits and lived experiences of green motherhood
Authors: Knibb Jana Nekesa , Taylor Kimberly
Published: April 2017

Purpose

This paper aims to understand the meanings, motivations and practices of green motherhood and, in particular, how green mothers incorporate this lifestyle into their consumption practices.

Design/methodology/approach

To address the research questions, a survey and focus group were conducted. Survey responses and transcribed focus group statements comprise the data.

Findings

Several variables explain the adoption of green motherhood for one consumer segment. Results showed the mothers’ greater concern about their own family’s health and safety, and a desire to reduce risk and gain some control over their world, rather than concern about the environment at large, drives their choices.

Research limitations/implications

The paper identifies and explores the consumption and mothering practices of a segment of “light green” moms and uncovers their motivations. Limitations include relatively small sample sizes.

Practical/implications

“Green mothers” are an important, emerging segment of green consumers, but they often face conflicting roles and expectations. The research adds to the literature on green consumerism by expanding the authors’ knowledge of the nuances and limitations of the green motherhood movement and delving deeper into the decision processes these mothers use. This information can help marketers seeking to target this segment with easy-to-use, convenient products which appeal to their concerns about controlling their environment and improving their family’s health.

Practical/implications

Understanding green consumption practices can help marketers or governmental organizations reach consumers who are motivated to be “green”, which, in turn, can lead to an improved environment.

Originality/value

The identification of the “light green” consumer segment is novel, and the paper uses a unique mixed methods approach. Greater understanding of the meaning and limitations of green motherhood is obtained.
Multichannel shopping well-being: a narrative-based examination
Authors: Harris Patricia
Published: April 2017

Purpose

The purpose of this research is to investigate whether and how shopping well-being emerges from multichannel shopping. The multichannel shopper has more choice of where, when and how to shop, and could potentially experience greater shopping well-being than the single-channel equivalent. On the other hand, it is possible that multichannel shopping creates levels of complexity for consumers in terms of their channel decision processes, and therefore, the potential increase in shopping well-being may not actually occur.

Design/methodology/approach

An interpretive approach is adopted and narratives are used to provide a focus on the multichannel shopper’s lived experiences. Narrative generation was conducted with 12 participant shoppers from across the UK in March and April 2016.

Findings

Multichannel retailing does not deliver universally enhanced shopping well-being. Findings suggest that while well-being is enhanced by some aspects of multichannel shopping, diminished well-being is a more frequent outcome. Six themes emerged from the narratives delineating aspects of multichannel shopping which diminish well-being: finding what you want; ease and flexibility; staying in control; getting a fair deal; pleasure and fulfilment; guilt, regret and annoyance.

Originality/value

This research makes three contributions to our understanding of shopping well-being: by providing more in-depth insight than previous studies, by examining all shopping activity rather than recreational/discretionary shopping and by examining shopping well-being from a multichannel rather than single-channel perspective.
Understanding customer participation in online brand communities
Authors: Kamboj Shampy , Rahman Zillur
Published: April 2017

Purpose

The purpose of this paper is to present a systematic review of customer participation research specifically in online brand communities and summarize a number of basic issues as important research gaps that future research should address.

Design/methodology/approach

By using the content analysis method, this paper explores, analyses and presents a literature review by closely examining 113 articles published during 2001-2016, primarily from the leading marketing and management journals.

Findings

The findings of this review show that regardless of the plenty of studies in this area, a conceptual framework for customer participation is undetermined. This review presents a framework describing various antecedents, mediators, moderators and consequences of online brand community participation. Apart from this, various theories and models used in the reviewed articles are being depicted. The literature classification presented in this paper portrays the current trends and patterns of research in this area. This review also addresses research gaps in this area and presents them in the form of future research directions.

Research/limitations/implications

This review of literature carried out by the authors suggests that customer participation in online brand communities needs more focused conceptual research and the implications of this study will help researchers in this direction. Moreover, the managers can use the identified variables as a checklist to their online brand communities’ activities.

Originality/value

This paper is the first to provide a systematic review of customer participation in online brand community area that presents a comprehensive knowledge regarding the current state of research in this area on a single platform and provides a conceptual framework.
Emotions and socially just teaching: a qualitative study
Authors: Ramezanzadeh Akram , Adel Seyyed Mohammad Reza , Zareian Gholamreza , Ghazanfari Mohammad
Published: April 2017

Purpose

The purpose of this paper is to explore Iranian EFL teachers’ and learners’ emotions in the realities of the classroom to investigate how their experience and navigation of emotions could provide the opportunity for socially just teaching.

Design/methodology/approach

A qualitative study was conducted to probe EFL teachers’ and learners’ emotional experiences. Data were gathered through interviews and observation. Using interpretive phenomenological analysis, the researchers analyzed the data through three stages of critical emotional praxis, including identification, reflection, and response.

Findings

Findings of the study revealed that emotions of caring, love, anger, and anxiety were the most dominant emotions among teachers and learners. Also, it was shown that the participants used emotion management, the cultivation of positive emotions, and bodily manipulation in order to change their course of actions and move toward two-way communication whereby they could see and hear each other.

Originality/value

The paper provided a new lens through which socially just teaching can be studies in EFL contexts. Also, the participants of the study consisted of both the teachers and the learners, because the researchers believed in a teacher’s identity as a pedagogy. In this respect, this study can also be considered as different from similar studies conducted on teachers’ emotional identities in the classroom.
A framework for modelling range shifts and migrations: asking when, whither, whether and will it return
Authors: Gurarie Eliezer , Cagnacci Francesca , Peters Wibke , Fleming Christen H. , Calabrese Justin M. , Mueller Thomas , Fagan William F.
Published: April 2017

Many animals undertake movements that are longer scaled and more directed than their typical home ranging behaviour. These movements include seasonal migrations (e.g. between breeding and feeding grounds), natal dispersal, nomadic range shifts and responses to local environmental disruptions. While various heuristic tools exist for identifying range shifts and migrations, none explicitly model the movement of the animals within a statistical framework that facilitates quantitative comparisons.

We present the mechanistic range shift analysis (MRSA), a method to estimate a suite of range shift parameters: times of initiation, duration of transitions, centroids and areas of respective ranges. The method can take the autocorrelation and irregular sampling that is characteristic of much movement data into account. The mechanistic parameters suggest an intuitive measure, the range shift index, for the extent of a range shift. The likelihood based estimation further allows for statistical tests of several relevant hypotheses, including a range shift test, a stopover test and a site fidelity test. The analysis tools are provided in anRpackage (marcher).

We applied the MRSA to a population of GPS tracked roe deer (Capreolus capreolus) in the Italian Alps between 2005 and 2008. With respect to seasonal migration, this population is extremely variable and difficult to classify. Using the MRSA, we were able to quantify the behaviours across the population and among individuals across years, identifying extents, durations and locations of seasonal range shifts, including cases that would have been ambiguous to detect using existing tools.

The strongest patterns were differences across years: many animals simply did not perform a seasonal migration to wintering grounds during the mild winter of 2006–2007, even though some of these same animals did move extensively in other, harsher winters. For seasonal migrants, however, site fidelity across years was extremely high, even after skipping an entire seasonal migration. These results suggest that for roe deer behavioural plasticity and tactical responses to immediate environmental cues are reflected in the decision ofwhetherrather thanwhereto migrate. The MRSA also revealed a trade‐off between the probability of migrating and the size of a home range.
Value orientations and social attitudes in the holistic milieu
Authors: Höllinger Franz
Published: April 2017

Based on a representative population survey for Germany this article investigates whether engagement in holistic activities is associated with privatized lifestyles and lack of social responsibility or with countercultural orientations and base‐democratic political commitment. To analyse this question, respondents who are engaged in holistic activities are divided into three groups that are compared with each other as well as with Christians and non‐religious people. The findings show that the three holistic groups are characterized by clearly different attitudinal patterns: Respondents engaged in body‐mind‐spirit activities have an affinity to self‐directed ways of life, post‐materialism and environmentalism. Holistic Christians try to combine the Christian ideal of altruism and post‐materialist orientations. Those who are attracted only to magical‐occult practices are primarily concerned with individualistic self‐improvement and correspond more to the image of the hedonist consumer at the esoteric marketplace.
Sustaining corporate class consciousness across the new liquid managerial elite in Britain
Authors: Davis Aeron
Published: April 2017

This article asks: how is class consciousness and cohesiveness amongst the UK business elite maintained in the twenty‐first century? Elite studies traditionally sought to account for the construction and circulation of dominant ideology through exclusive education systems, institutional board interlocks and club memberships. The problem is that business elite membership of all these institutions has been steady declining in recent decades. Contemporary corporate elites now appear more mobile and fragmented in an age of globalization. However, class cohesion amongst business leaders appears as strong as ever after decades of neoliberal policy hegemony. So, how are such ideas, norms and values circulated and maintained? This study tried to answer this question drawing on a set of 30 semi‐structured interviews with top UK CEOs and a demographic audit of current FTSE 100 CEOs. The findings suggest that three additional means of achieving business elite coherence have become more significant: professional business education, semi‐formal but regular meeting sites, and specialist business media.
Effects of clopidogrel on inflammatory cytokines and adhesion molecules in human endothelial cells: Role of nitric oxide mediating pleiotropic effects
Authors: Cerda Alvaro , Pavez Monica , Manriquez Victor , Luchessi Andre Ducati , Leal Pamela , Benavente Felipe , Fajardo Cristina Moreno , Salazar Luis , Hirata Mario Hiroyuki , Hirata Rosario Dominguez Crespo
Published: April 2017

Introduction

Clopidogrel is commonly used in prevention and treatment of atherothrombosis. Some previous studies have suggested a pleiotropic effect of clopidogrel; however, when this drug causes platelet‐independent effects on endothelial function remains unclear.

Aims

To evaluate the influence of clopidogrel on inflammatory biomarkers and adhesion molecules in human endothelial cells and the role of nitric oxide (NO) in this process.

Methods

TNF‐α‐induced human umbilical vein endothelial cells (HUVEC) were exposed to clopidogrel. Gene expression and protein expression of ICAM‐1, P‐selectin, IL‐8, IL‐6, and MCP‐1 were evaluated by qPCR, flux cytometry, or milliplex technology. Expression of endothelial nitric oxide synthase (NOS3) and NO release were also evaluated. Influence of clopidogrel was further evaluated in NOS3 downregulated HUVEC by RNAi.

Results

Clopidogrel at 20 μmol/L induced NO release in HUVEC after 24‐hours treatment. Gene expressions of inflammatory markers IL‐8 and MCP1 were reduced after clopidogrel treatment (P<.05); however, only MCP‐1 remained reduced at protein level. IL‐6 was not modified by clopidogrel treatment. Gene expression and protein expression of ICAM‐1 were diminished by 24‐hours clopidogrel exposure, whereas P‐selectin was not modified. NOS3 downregulated HUVEC model revealed that ICAM‐1 modification by clopidogrel is dependent of this via, whereas MCP‐1 is modulated in an NO‐independent form.

Conclusions

Our results support new evidence for pleiotropic effects of clopidogrel on inflammation and endothelial function. Reduction in ICAM‐1 and MCP‐1 in human endothelium is an important extent of the use of this drug for treatment of cardiovascular diseases, and NO has an important role in this process.
What about winter? Integrating the missing season into climate change experiments in seasonally snow covered ecosystems
Authors: Sanders‐DeMott Rebecca , Templer Pamela H.
Published: April 2017

Ecosystem‐scale climate warming experiments have provided insight into the future dynamics of terrestrial ecosystems. In seasonally snow covered regions, changes in winter soil temperatures are largely mediated through shifts in depth and duration of snowpack that have implications for ecosystem processes. Despite known effects of changes in snowpack dynamics on ecosystem processes in seasonally snow covered environments, the extent to which warming experiments address winter climate change is unclear. Identifying how previous warming studies have addressed changes in winter climate is important for understanding what is known about interacting effects of climate change across seasons and to highlight gaps in our understanding of ecosystem responses to climate change throughout the year.

We reviewed 64 published ecosystem‐scale climate change manipulation experiments spanning three decades that were conducted in seasonally snow covered regions and simulated warmer growing season temperatures.

We found that only 20% of experiments in snow covered ecosystems explicitly manipulated the winter climate to reflect projected changes in winter soil temperatures mediated through changes in snowpack over the next several decades. Experiments that manipulated both winter and the growing season climate employed a variety of passive and active warming methods. Above‐ground active methods most realistically simulated projected changes in soil temperature that will be mediated through changes in snow cover. Experiments with distinct winter treatments were distributed among tundra, forest, grassland and wetland ecosystems and together show that shifts in winter climate have a strong influence on, and in some cases offset, observed responses to experimental warming in the growing season alone or across the year.

By designing climate change experiments that examine the effects of winter and growing season climate change together, there is an opportunity to develop a better mechanistic understanding and more accurate projections of ecosystem responses to climate change that would not be evident from examining changes in either season alone.
Visual impairment certification due to diabetic retinopathy in North and Eastern Devon
Authors: Lin Siying , Gupta Bhaskar , James Natalee , Ling Roland H.
Published: April 2017

Purpose

To determine certifications of visual impairment (CVIs) due to diabetic retinopathy (DR) in a region that has operated diabetic screening since 1992.

Methods

A retrospective review of all CVIs due to DR was conducted, with mid‐year population estimates and a diabetes prevalence model used to determine the annual incidence of certification from 2010 to 2013. For 2013, CVIs due to DR were also compared to all CVIs in the region.

Results

The total number of certifications due to DR was 75; 52 were sight impaired (SI) and 23 severely sight impaired (SSI) certifications; 25% of patients had type 1, and 75% had type 2 diabetes mellitus. The mean age at time of CVI was 65.5 years. The mean duration of known diabetes was 22.0 years. The incidence of CVI due to DR ranged from 30.8 to 77.4 per million population per year between 2010 and 2013. The incidence of CVI in the diabetic population was estimated at 0.47 to 1.21 per 1000 patients per year with diabetes for 2010–2013. In 2013, DR was a main or contributing cause in 4.3% of all CVIs, but did not contribute to any SSI certifications in the working age population.

Conclusion

The incidence of CVI due to DR was comparable to that reported in other regions. Nationwide, DR was the second most common cause of blindness in working age adults, but did not contribute to any SSI certifications in our population. Our results are consistent with the success of a long‐standing retinal screening programme.
Statins and polyneuropathy revisited: case‐control study in Denmark, 1999–2013
Authors: Svendsen Toke de Koning , Nørregaard Hansen Peter , García Rodríguez Luis Alberto , Andersen Lene , Hallas Jesper , Sindrup Søren Hein , Gaist David
Published: April 2017

Aim

In a previous study, we found a positive association between statin use and polyneuropathy risk. Other studies reported equivocal results. The present study aimed to confirm our findings with a design similar to that used in our previous study but with a larger data set.

Methods

We searched medical registry data to identify patients diagnosed with incident polyneuropathy of no known cause (idiopathic polyneuropathy) between 1999 and 2013; we verified diagnoses through medical records. For each case, we recruited 20 general population controls with no previous history of polyneuropathy. Controls were matched to their respective case for age and gender. We ascertained the prior statin use of cases and controls through a prescription registry. Based on this information, exposure to statins was categorized into ‘ever use’ or ‘never use’. Ever use of statins was classified by how recently they had been used (‘current use’ or ‘past use’); current use was further classified into long‐term use (5+ years) and high‐ or low‐intensity use. We used conditional logistic regression to calculate odds ratios (ORs) with 95% confidence intervals (CIs) to examine associations between polyneuropathy and statin use.

Results

We included 370 validated cases and 7400 controls. Ever use of statins was not associated with an elevated risk of polyneuropathy (OR 1.14, 95% CI 0.84, 1.54). Similarly, we found no associations between polyneuropathy risk and current use (OR 1.11, 95% CI 0.79, 1.53), long‐term use (OR 1.13, 95% CI 0.66, 1.92) or high‐intensity statin use (OR 1.05, 95% CI 0.59, 1.84).

Conclusion

Statin use was not associated with an increased risk of idiopathic polyneuropathy.
Cenozoic evolution of the Altyn Tagh and East Kunlun fault zones inferred from detrital garnet, tourmaline and rutile in southwestern Qaidam Basin (Northern Tibetan Plateau)
Authors: Li Linlin , Wu Chaodong , Yu Xiangjiang
Published: April 2017

This study focuses on the Cenozoic provenance and tectonic evolution of the southwestern Qaidam Basin through geochemical analysis of detrital garnet, tourmaline and rutile. The variation of detrital mineral compositions indicates that the Cenozoic evolution can be divided into three stages: (i) before the deposition of the upper Xiaganchaigou Formation (before 37.8 Ma); (ii) between the deposition of the upper Xiaganchaigou Formation and the Shangganchaigou Formation (from 37.8 to 22 Ma); (iii) since the deposition of the Xiayoushashan Formation (since 22 Ma). In the first stage, abundant garnets from high‐grade meta‐basic and ultramafic rocks in the sediments from the Ganchaigou area support a provenance from the South Altyn Tagh HP/UHP metamorphic zone. The low percentage of tourmalines from granitoid rocks in the sediments in the Kunbei‐Lücaotan area suggests a provenance from the East Kunlun fault zone, indicating that the Qimen Tagh Shan was not high enough to prevent the transport of sediments from the southern Qaidam Basin. The sediments in the Qigequan area were derived from both the Altyn Tagh fault zone and the East Kunlun fault zone. In the second stage, the tectonic activity consisted in the rapid uplift of the Altyn Shan. Changes in garnet composition indicate a lower detrital contribution from high‐grade metamorphic rocks. In the third stage, the disappearance of garnets from high‐grade metamorphic rocks and scattered temperatures of rutiles in the Ganchaigou area suggest that the source area shifted from the South Altyn Tagh HP/UHP metamorphic rocks to weakly metamorphosed Meso‐Neoproterozoic sedimentary rocks. The increase in granitoid‐derived tourmalines in the Kunbei‐Lücaotan area is indicative of the rapid uplift of the Qimen Tagh Shan. The provenance evolution in the southwestern Qaidam Basin indicates that the tectonic activity along the Altyn Tagh fault zone can be divided into an early stage of Altyn Shan uplift and a later stage of left‐lateral slip. At the same time, tectonic movement along the East Kunlun fault zone initiated.
M2‐like macrophage polarization in high lactic acid‐producing head and neck cancer
Authors: Ohashi Toshimitsu , Aoki Mitsuhiro , Tomita Hiroyuki , Akazawa Takashi , Sato Katsuya , Kuze Bunya , Mizuta Keisuke , Hara Akira , Nagaoka Hitoshi , Inoue Norimitsu , Ito Yatsuji
Published: April 2017

Reprogramming of glucose metabolism in tumor cells is referred to as the Warburg effect and results in increased lactic acid secretion into the tumor microenvironment. We have previously shown that lactic acid has important roles as a pro‐inflammatory and immunosuppressive mediator and promotes tumor progression. In this study, we examined the relationship between the lactic acid concentration and expression of LDHA and GLUT1, which are related to the Warburg effect, in human head and neck squamous cell carcinoma (HNSCC). Tumors expressing lower levels of LDHA and GLUT1 had a higher concentration of lactic acid than those with higher LDHA and GLUT1 expression. Lactic acid also suppressed the expression of LDHA and GLUT1 in vitro. We previously reported that lactic acid enhances expression of an M2 macrophage marker, ARG1, in murine macrophages. Therefore, we investigated the relationship between the lactic acid concentration and polarization of M2 macrophages in HNSCC by measuring the expression of M2 macrophage markers, CSF1R and CD163, normalized using a pan‐macrophage marker, CD68. Tumors with lower levels of CD68 showed a higher concentration of lactic acid, whereas those with higher levels of CSF1R showed a significantly higher concentration of lactic acid. A similar tendency was observed for CD163. These results suggest that tumor‐secreted lactic acid is linked to the reduction of macrophages in tumors and promotes induction of M2‐like macrophage polarization in human HNSCC.
Intratumoral bidirectional transitions between epithelial and mesenchymal cells in triple‐negative breast cancer
Authors: Yamamoto Mizuki , Sakane Kota , Tominaga Kana , Gotoh Noriko , Niwa Takayoshi , Kikuchi Yasuko , Tada Keiichiro , Goshima Naoki , Semba Kentaro , Inoue Jun‐ichiro
Published: April 2017

Epithelial–mesenchymal transition (EMT) and its reverse process, mesenchymal–epithelial transition MET, are crucial in several stages of cancer metastasis. Epithelial–mesenchymal transition allows cancer cells to move to proximal blood vessels for intravasation. However, because EMT and MET processes are dynamic, mesenchymal cancer cells are likely to undergo MET transiently and subsequently re‐undergo EMT to restart the metastatic process. Therefore, spatiotemporally coordinated mutual regulation between EMT and MET could occur during metastasis. To elucidate such regulation, we chose HCC38, a human triple‐negative breast cancer cell line, because HCC38 is composed of epithelial and mesenchymal populations at a fixed ratio even though mesenchymal cells proliferate significantly more slowly than epithelial cells. We purified epithelial and mesenchymal cells from Venus‐labeled and unlabeled HCC38 cells and mixed them at various ratios to follow EMT and MET. Using this system, we found that the efficiency of EMT is approximately an order of magnitude higher than that of MET and that the two populations significantly enhance the transition of cells from the other population to their own. In addition, knockdown of Zinc finger E‐box‐binding homeobox 1 (ZEB1) or Zinc finger protein SNAI2 (SLUG) significantly suppressed EMT but promoted partial MET, indicating that ZEB1 and SLUG are crucial to EMT and MET. We also show that primary breast cancer cells underwent EMT that correlated with changes in expression profiles of genes determining EMT status and breast cancer subtype. These changes were very similar to those observed in EMT in HCC38 cells. Consequently, we propose HCC38 as a suitable model to analyze EMT–MET dynamics that could affect the development of triple‐negative breast cancer.
Chimerism-based tolerance in organ transplantation: preclinical and clinical studies
Authors: Oura T , Cosimi A B , Kawai T
Published: April 2017

Induction of allograft tolerance has been considered the ultimate goal in organ transplantation. Although numerous protocols to induce allograft tolerance have been reported in mice, a chimerism-based approach through donor haematopoietic stem cell transplantation has been the only approach to date that induced allograft tolerance reproducibly following kidney transplantation in man. Renal allograft tolerance has been achieved by induction of either transient mixed chimerism or persistent full donor chimerism. Although the risk of rejection may be low in tolerance achieved via durable full donor chimerism, the development of graft-versus-host disease (GVHD) has limited the wider clinical application of this approach. In contrast, tolerance induced by transient mixed chimerism has not been associated with GVHD, but the risk of allograft rejection is more difficult to predict after the disappearance of haematopoietic chimerism. Current efforts are directed towards the development of more clinically feasible and reliable approaches to induce more durable mixed chimerism in order to widen the clinical applicability of these treatment regimens.
Janus kinase inhibitors prevent migration of rheumatoid arthritis neutrophils towards interleukin-8, but do not inhibit priming of the respiratory burst or reactive oxygen species production
Authors: Mitchell T S , Moots R J , Wright H L
Published: April 2017

Neutrophils play a crucial role in the pathophysiology of rheumatoid arthritis (RA) via the release of reactive oxygen species (ROS), proteases and cytokines. Orally active Janus kinase (JAK) inhibitors (JAKi), e.g. baricitinib and tofacitinib, have high clinical efficacy in RA but are linked with neutropenia and increased infections. Our aim was to determine the effect of JAK inhibition with baricitinib and tofacitinib on healthy control and RA neutrophil lifespan and function. RA (n = 7) and healthy control (n = 7) neutrophils were treated with baricitinib or tofacitinib for 30 min, prior to incubation in the absence or presence of granulocyte–macrophage colony-stimulating factor (GM-CSF) or interferon (IFN)-γ. JAKi prevented GM-CSF- and IFN-γ-induced apoptosis delay in RA and healthy control neutrophils in a dose-dependent manner. Baricitinib decreased the rate of chemotaxis towards interleukin (IL)-8, but not f-Met-Leu-Phe (fMLP) in RA neutrophils. While healthy control neutrophils incubated with GM-CSF became primed to produce ROS in response to stimulation with fMLP and phorbol-12-myristate-12-acetate (PMA), RA neutrophils produced increased levels of ROS without the need for priming. JAKi prevented ROS release from primed healthy control neutrophils in response to fMLP, but had no effect on ROS production by RA neutrophils. Baricitinib reversed GM-CSF priming of ROS production in response to fMLP in healthy control, but not RA, neutrophils. We conclude that incubation with JAKi prevents chemotaxis of RA neutrophils towards IL-8, but does not prevent the production of ROS or increase the level of apoptosis. This may be due to the in-vivo exposure of RA neutrophils to priming agents other than those that activate JAK/signal transducer and activator of transcription (STAT) signalling.
Increased interleukin (IL)-20 and IL-24 target osteoblasts and synovial monocytes in spondyloarthritis
Authors: Kragstrup T W , Andersen M N , Schiøttz-Christensen B , Jurik A G , Hvid M , Deleuran B
Published: April 2017

The pathogenesis of spondyloarthritis (SpA) involves activation of the innate immune system, inflammation and new bone formation. The two cytokines interleukin (IL)-20 and IL-24 have been shown to link innate immune activation and tissue homeostasis. We hypothesized that these two cytokines are secreted as part of activation of the innate immune system and affect bone homeostasis in SpA. IL-20 and IL-24 were measured in plasma from axial SpA patients (n = 83). Peripheral SpA patients (n = 16) were included for in-vitro cell culture studies. The plasma IL-20 and IL-24 levels were increased in SpA patients compared with healthy controls (HCs) by 57 and 83%, respectively (both P < 0·0001). The Toll-like receptor 4-induced secretion of the two cytokines was greater in SpA peripheral blood mononuclear cells (PBMCs) compared with HC PBMCs. IL-20 and IL-24 increased the production of monocyte chemoattractant protein-1 by activated SpA synovial fluid monocytes, decreased the production of Dickkopf-1 by SpA fibroblast-like synovial cells and induced mineralization in human osteoblasts. Taken together, our findings indicate disease-aggravating functions of IL-20 and IL-24 in SpA.
Heat shock transcription factor 1 promotes the proliferation, migration and invasion of osteosarcoma cells
Authors: Zhou Zhenhua , Li Yan , Jia Qi , Wang Zhiwei , Wang Xudong , Hu Jingjing , Xiao Jianru
Published: April 2017

Objectives

Osteosarcoma is the most commonly diagnosed primary malignancy of bone and its overall survival rate is still very low. The molecular mechanisms underlying the progression of osteosarcoma have not been clearly illuminated. Heat shock transcription factor 1 (HSF1) is a key regulator of the heat shock response and also plays important roles in many cancers, but its function in osteosarcoma remains unexplored.

Materials and methods

In this study, the proliferation of osteosarcoma cells was determined by Cell Counting Kit‐8 assays and colony formation assays. Transwell assays were used to demonstrate the migration and invasion abilities of osteosarcoma cells. A tumour formation assay in a nude mouse model was performed to assess the effect of HSF1 on osteosarcoma cell growth in vivo. The protein levels of HSF1 were analysed with immunohistochemical staining in samples from osteosarcoma patients.

Results

We demonstrated that knockdown of HSF1 reduced the proliferation, migration and invasion of osteosarcoma cells, while overexpression of HSF1 promoted the proliferation, migration and invasion of osteosarcoma cells. Furthermore, HSF1 promoted the proliferation of osteosarcoma cells in vivo. In addition, high levels of HSF1 were associated with a poor prognosis in osteosarcoma.

Conclusions

These data highlight an important role of HSF1 in proliferation, migration and invasion of osteosarcoma cells. Moreover, the expression of HSF1 was associated with prognosis in osteosarcoma.
Changing epidemiology of elderly small cell lung cancer patients over the last 40 years; a SEER database analysis
Authors: Abdel‐Rahman Omar
Published: April 2017

Background

Small cell lung cancer (SCLC) is a distinct clinical and pathological entity within the spectrum of lung cancer. It was observed that the relative age distribution of the disease changed over years.

Methods

Surveillance, epidemiology, and end results (SEER) database (1973‐2013) was utilized to determine the incidence, presentation and treatment outcomes of elderly patients (>70 years) with SCLC. Join point regression analysis was then conducted to analyze age‐adjusted trends in incidence for the elderly as well as the whole SCLC population. Survival analysis was conducted through Kaplan–Meier analysis. Clinicopathological characteristics and survival outcomes were compared between patients diagnosed at 70‐79 years old and those older than 80 years old (octogenarian group).

Results

The proportion of elderly patients among all cases of SCLC increased from 23% in 1975 to 44% in 2010. Moreover, the proportion of elderly female patients among all cases of elderly SCLC increased from 25% in 1975 to 49% in 2010. When categorizing patients into four subgroups “70‐74,” “75‐79,” “80‐84,” and “85+”, there was a trend toward a lower cancer‐specific survival with increasing age (P < .0001). A limited improvement in 5 year survival was observed during the study period and it is less apparent as the age increases.

Conclusion

The proportion of elderly patients among all cases of SCLC has increased over the past 40 years. Further studies are needed to better select appropriate treatments for this subset of patients.
Parallel evolution of behaviour during independent host‐shifts following maize introduction into Asia and Europe
Authors: Calcagno Vincent , Mitoyen Clémentine , Audiot Philippe , Ponsard Sergine , Gao Gui‐Zhen , Lu Zhao‐Zhi , Wang Zhen‐Ying , He Kang‐Lai , Bourguet Denis
Published: April 2017

Maize was introduced into opposite sides of Eurasia 500 years ago, in Western Europe and in Asia. This caused two host‐shifts in the phytophagous genus Ostrinia; O. nubilalis (the European corn borer; ECB) and O. furnacalis (the Asian corn borer; ACB) are now major pests of maize worldwide. They originated independently from Dicot‐feeding ancestors, similar to O. scapulalis (the Adzuki bean borer; ABB). Unlike other host‐plants, maize is yearly harvested, and harvesting practices impose severe mortality on larvae found above the cut‐off line. Positive geotaxis in the ECB has been proposed as a behavioural adaptation to harvesting practices, allowing larvae to move below the cut‐off line and thus escape harvest mortality. Here, we test whether the same behavioural adaptation evolved independently in Europe and in Asia. We sampled eight genetically differentiated ECB, ACB and ABB populations in France and China and monitored geotaxis through the entire larval development in artificial stacks mimicking maize stems. We find that all ECB and ACB populations show a similar tendency to move down during the latest larval stages, a behaviour not observed in any European or Asian ABB population. The behaviour is robustly expressed regardless of larval density, development mode or environmental conditions. Our results indicate that maize introduction triggered parallel behavioural adaptations in Europe and Asia, harvest selection presumably being the main driver.
Biomass responses in a temperate European grassland through 17 years of elevated CO2
Authors: Andresen Louise C. , Yuan Naiming , Seibert Ruben , Moser Gerald , Kammann Claudia I. , Luterbacher Jürg , Erbs Martin , Müller Christoph
Published: April 2017

Future increase in atmospheric CO2 concentrations will potentially enhance grassland biomass production and shift the functional group composition with consequences for ecosystem functioning. In the “GiFACE” experiment (Giessen Free Air Carbon dioxide Enrichment), fertilized grassland plots were fumigated with elevated CO2 (eCO2) year‐round during daylight hours since 1998, at a level of +20% relative to ambient concentrations (in 1998, aCO2 was 364 ppm and eCO2 399 ppm; in 2014, aCO2 was 397 ppm and eCO2 518 ppm). Harvests were conducted twice annually through 23 years including 17 years with eCO2 (1998 to 2014). Biomass consisted of C3 grasses and forbs, with a small proportion of legumes. The total aboveground biomass (TAB) was significantly increased under eCO2 (p = .045 and .025, at first and second harvest). The dominant plant functional group grasses responded positively at the start, but for forbs, the effect of eCO2 started out as a negative response. The increase in TAB in response to eCO2 was approximately 15% during the period from 2006 to 2014, suggesting that there was no attenuation of eCO2 effects over time, tentatively a consequence of the fertilization management. Biomass and soil moisture responses were closely linked. The soil moisture surplus (c. 3%) in eCO2 manifested in the latter years was associated with a positive biomass response of both functional groups. The direction of the biomass response of the functional group forbs changed over the experimental duration, intensified by extreme weather conditions, pointing to the need of long‐term field studies for obtaining reliable responses of perennial ecosystems to eCO2 and as a basis for model development.
Evaluation of splenic perfusion and spleen size using dynamic computed tomography: Usefulness in assessing degree of liver fibrosis
Authors: Suzuki Takeshi , Yamada Akira , Komatsu Daisuke , Kurozumi Masahiro , Fujinaga Yasunari , Ueda Kazuhiko , Miyagawa Shinichi , Kadoya Masumi
Published: April 2017

Aim

To enhance the usefulness of splenic perfusion evaluated by means of dynamic computed tomography (CT) and spleen size in assessing the degree of liver fibrosis.

Methods

We retrospectively studied 133 patients who had undergone dynamic CT before hepatectomy. Fibrosis was histologically established in all. First we calculated splenic perfusion parameters K1 (inflow rate constant), 1/k2 (mean transit time; MTT), and K1/k2 (distribution volume; Vd), using compartment model analysis. Then we compared the stage of fibrosis with splenic perfusion and spleen size (long axis, R), using the Kruskal–Wallis test and multiple comparisons. After that, we assessed the diagnostic accuracy of the combination of splenic perfusion, spleen size, age, gender, and the presence or absence of hepatitis B and hepatitis C viral infection in detecting liver fibrosis, using stepwise regression and receiver operating characteristic analysis.

Results

Significant differences (P < 0.05) in MTT were observed in comparisons between fibrosis stages F0 and F4, between F1 and F4, and between F2 and F4. Significant differences (P < 0.05) in R were observed in comparisons between F0 and F4, and between F1 and F4. Considering the presence or absence of hepatitis B and C viral infection along with MTT and R, the areas under the receiver operating characteristic curves were 0.89 for ≥F1, 0.83 for ≥F2, 0.82 for ≥F3, and 0.82 for F4.

Conclusion

Splenic MTT and spleen size are helpful in assessing liver fibrosis.
Trajectory of systolic blood pressure in a low‐income, racial‐ethnic minority cohort with diabetes and baseline uncontrolled hypertension
Authors: Zullig Leah L. , Liang Yuanyuan , Vale Arismendez Shruthi , Trevino Aron , Bosworth Hayden B. , Turner Barbara J.
Published: April 2017

In two primary care clinics in Texas serving low‐income patients, systolic blood pressure (SBP) trajectory was examined during 2 years in patients with diabetes mellitus (mean SBP ≥140 mm Hg: 152 mm Hg±11.2 in the baseline year). Among 860 eligible patients, 62.0% were women, 78.8% were Hispanic, and 41.2% were uninsured. Overall, SBP dropped 0.56 mm Hg per month or 13.4 mm Hg by 24 months. For patients with mean glycated hemoglobin ≥9% in year 1, SBP declined 4.8 mm Hg less by 24 months vs those with glycated hemoglobin <7% (P=.03). Compared with white women, SPB declined 7.2 mm Hg less by 24 months in Hispanic women (P=.03) and 9.6 mm Hg less by 24 months in black men (P=.04). SBP also declined 9.1 mm Hg less by 24 months for patients taking four or more blood pressure drug classes at baseline vs one drug class. In this low‐income cohort, clinically complex patients and racial‐ethnic minorities had clinically significantly smaller declines in SBP.
The Icatibant Outcome Survey: experience of hereditary angioedema management from six European countries
Authors: Caballero T. , Aberer W. , Longhurst H.J. , Maurer M. , Zanichelli A. , Perrin A. , Bouillet L. , Andresen I. ,   the IOS Study Group
Published: April 2017

Background

Hereditary angioedema (HAE) due to C1‐inhibitor deficiency (C1‐INH‐HAE) is a rare, potentially fatal, bradykinin‐mediated disease. Icatibant is a bradykinin B2 receptor antagonist originally approved in 2008 in the European Union and 2011 in the United States as an acute therapy option for HAE attacks in adults.

Objective

To compare demographics, disease characteristics and treatment outcomes of icatibant‐treated HAE attacks in patients with C1‐INH‐HAE enrolled in the Icatibant Outcome Survey across six European countries: Austria, France, Germany, Italy, Spain and the UK.

Methods

The Icatibant Outcome Survey [IOS; Shire, Zug, Switzerland (NCT01034969)] is an international observational study monitoring the safety and effectiveness of icatibant. Descriptive, retrospective analyses compared IOS country data derived during July 2009–April 2015.

Results

Overall, 481 patients with C1‐INH‐HAE provided demographic data. A significant difference across countries in age at onset (P = 0.003) and baseline attack frequency (P < 0.001) was found although no significant differences were found with respect to gender (majority female; P = 0.109), age at diagnosis (P = 0.182) or delay in diagnosis (P = 0.059). Icatibant was used to treat 1893 attacks in 325 patients with majority self‐administration in all countries. Overall, significant differences (all P < 0.001) were found across countries in time to treatment [median 1.8 h; median range: 0.0 (Germany–Austria) to 4.4 (France) h], time to resolution [median 6.5 h; median range: 3 (Germany–Austria) to 12 (France) h] and attack duration [median 10.5 h; median range: 3.1 (Germany–Austria) to 18.5 (France) h].

Conclusion

These data form the first European cross‐country comparison of disease characteristics and icatibant use in patients with C1‐INH‐HAE who are enrolled in IOS. International variation in icatibant practice and treatment outcomes across the six European countries assessed highlight the need to further investigate the range of country‐specific parameters driving regional variations in icatibant use.
Diagnostic accuracy of confocal microscopy imaging vs. punch biopsy for diagnosing and subtyping basal cell carcinoma
Authors: Kadouch D.J. , Leeflang M.M. , Elshot Y.S. , Longo C. , Ulrich M. , van der Wal A.C. , Wolkerstorfer A. , Bekkenk M.W. , de Rie M.A.
Published: April 2017

Background

In vivo reflectance confocal microscopy (RCM) is a promising non‐invasive skin imaging technique that could facilitate early diagnosis of basal cell carcinoma (BCC) instead of routine punch biopsies. However, the clinical value and utility of RCM vs. a punch biopsy in diagnosing and subtyping BCC is unknown.

Objective

To assess diagnostic accuracy of RCM vs. punch biopsy for diagnosing and subtyping clinically suspected primary BCC.

Methods

A prospective, consecutive cohort of 100 patients with clinically suspected BCC were included at two tertiary hospitals in Amsterdam, the Netherlands, between 3 February 2015 and 2 October 2015. Patients were randomized between two test‐treatment pathways: diagnosing and subtyping using RCM imaging followed by direct surgical excision (RCM one‐stop‐shop) or planned excision based upon the histological diagnosis and subtype of punch biopsy (standard care). The primary outcome was the agreement between the index tests (RCM vs. punch biopsy) and reference standard (excision specimen) in correctly diagnosing BCC. The secondary outcome was the agreement between the index tests and reference standard in correctly identifying the most aggressive BCC subtypes.

Results

Sensitivity to detect BCC was similar for RCM and punch biopsy (100% vs. 93.94%), but a punch biopsy was more specific than RCM (79% vs. 38%). RCM expert evaluation for diagnosing BCC had a sensitivity of 100% and a specificity of 75%. The agreement between RCM and excision specimen in identifying the most aggressive BCC subtype ranged from 50% to 85% vs. 77% by a punch biopsy.

Conclusion

Reflectance confocal microscopy and punch biopsy have comparable diagnostic accuracy to diagnose and subtype BCC depending on RCM experience. Although experienced RCM users could accurately diagnose BCC at a distance, we found an important difference in subtyping BCC. Future RCM studies need to focus on diagnostic accuracy, reliability and specific criteria to improve BCC subtype differentiation.
Genomic inferences of domestication events are corroborated by written records in Brassica rapa
Authors: Qi Xinshuai , An Hong , Ragsdale Aaron P. , Hall Tara E. , Gutenkunst Ryan N. , Chris Pires J. , Barker Michael S.
Published: April 2017

Demographic modelling is often used with population genomic data to infer the relationships and ages among populations. However, relatively few analyses are able to validate these inferences with independent data. Here, we leverage written records that describe distinct Brassica rapa crops to corroborate demographic models of domestication. Brassica rapa crops are renowned for their outstanding morphological diversity, but the relationships and order of domestication remain unclear. We generated genomewide SNPs from 126 accessions collected globally using high‐throughput transcriptome data. Analyses of more than 31,000 SNPs across the B. rapa genome revealed evidence for five distinct genetic groups and supported a European–Central Asian origin of B. rapa crops. Our results supported the traditionally recognized South Asian and East Asian B. rapa groups with evidence that pak choi, Chinese cabbage and yellow sarson are likely monophyletic groups. In contrast, the oil‐type B. rapa subsp. oleifera and brown sarson were polyphyletic. We also found no evidence to support the contention that rapini is the wild type or the earliest domesticated subspecies of B. rapa. Demographic analyses suggested that B. rapa was introduced to Asia 2,400–4,100 years ago, and that Chinese cabbage originated 1,200–2,100 years ago via admixture of pak choi and European–Central Asian B. rapa. We also inferred significantly different levels of founder effect among the B. rapa subspecies. Written records from antiquity that document these crops are consistent with these inferences. The concordance between our age estimates of domestication events with historical records provides unique support for our demographic inferences.
Tau aggregates: where, when, why and what consequences?
Authors: Frosch M. P.
Published: April 2017

The significance of tau pathology in the locus coeruleus and dorsal raphe nucleus in Alzheimer's disease is considered, both in terms of our understanding of disease mechanisms, and also the implications for treatment strategies.