bluuebunny/crossref_metadata_2025 huggingface dataset:
A Regression-based Framework for Scalable Pathway-guided Search in Genome-wide Association Studies
Authors: Biswas Shrayashi , Pal Soumen , Bhattacharjee Samsiddhi
Published: December 2017

Traditional unbiased genome-wide association studies (GWAS) have successfully identified thousands of loci associated with various complex diseases but there is evidence to suggest that many variants were missed at stringent genome-wide thresholds. Fortunately, there is a rapidly increasing amount of prior knowledge in publicly available genomic datasets and biological databases that can be harnessed to enhance the power of discovering SNPs/Genes from existing or new GWAS datasets. For most diseases, many of the identified loci tend to cluster into a few specific biological pathways/networks. From the point of view of disease etiology, such clustering is generally to be expected. This phenomenon can be exploited to conduct a more powerful genome-wide scan that is tailored to identify loci that are interconnected in pathways. We propose a scalable regression-based analytical framework to enable such a pathway-guided GWAS and demonstrate that it provides significant gains in power to detect disease associated SNPs. Our method requires two inputs, namely a) genome-wide summary level data (e.g., SNP p-values) and b) a grouping of genes into biologically meaningful categories (e.g., a database of pathways). It automatically adjusts the input p-values by incorporating the knowledge derived adaptively from the data and the pathways specified. The method involves a regularized logistic regression analysis to derive priors of each SNP and then re-weights the p-values of SNPs so as to maximize overall power of making discoveries. It increases the power to discover SNPs co-clustering into some of these pathways, while maintaining the global type-1 error (FWER) at the desired level. We used whole-genome simulations and summary data from real GWA studies of psoriasis, SLE, coronary artery disease and type-2 diabetes to illustrate the power improvement achieved by pathway-guided search. Our pipeline implemented as an R package can flexibly handle large number of prior annotations possibly derived from multiple databases.
Myopic control of neural dynamics
Authors: Hocker David , Park Il Memming
Published: December 2017

Manipulating the dynamics of neural systems through targeted stimulation is a frontier of research and clinical neuroscience; however, the control schemes considered for neural systems are mismatched for the unique needs of manipulating neural dynamics. An appropriate control method should respect the variability in neural systems, incorporating moment to moment “input” to the neural dynamics and behaving based on the current neural state, irrespective of the past trajectory. We propose such a controller under a nonlinear state-space feedback framework that steers one dynamical system to function as through it were another dynamical system entirely. This “myopic” controller is formulated through a novel variant of a model reference control cost that manipulates dynamics in a short-sighted manner that only sets a target trajectory of a single time step into the future (hence its myopic nature), which omits the need to pre-calculate a rigid and computationally costly neural feedback control solution. To demonstrate the breadth of this control’s utility, two examples with distinctly different applications in neuroscience are studied. First, we show the myopic control’s utility to probe the causal link between dynamics and behavior for cognitive processes by transforming a winner-take-all decision-making system to operate as a robust neural integrator of evidence. Second, an unhealthy motor-like system containing an unwanted beta-oscillation spiral attractor is controlled to function as a healthy motor system, a relevant clinical example for neurological disorders.
The Class I E3 Ubiquitin Ligase TRIM67 Modulates Brain Development and Behavior
Authors: Boyer Nicholas P. , Monkiewicz Caroline , Moy Sheryl S. , Gupton Stephanie L.
Published: December 2017

Specific class I members of the TRIM family of E3 ubiquitin ligases have been implicated in neuronal development from invertebrates to mammals. The single invertebrate class I TRIM and mammalian TRIM9 regulate axon branching and guidance in response to the axon guidance cue netrin-1, whereas mammalian TRIM46 establishes the axon initial segment. In humans, mutations in TRIM1 and TRIM18 are implicated in Optiz Syndrome, characterized by midline defects and often mild intellectual disability. TRIM67 is the most evolutionarily conserved vertebrate class I TRIM, yet is the least studied. Here we show that TRIM67 interacts with both its closest paralog TRIM9 and the netrin receptor DCC, and is differentially enriched in specific brain regions at specific developmental points. We describe the anatomical and behavioral consequences of deletion of murine Trim67. While viable, mice lacking Trim67 display severe impairments in spatial memory, cognitive flexibility, social novelty preference, muscle function and sensorimotor gating. Additionally, they exhibit abnormal anatomy of several brain regions, including the hippocampus, striatum and thalamus, as well as the corpus callosum. This study demonstrates the necessity for TRIM67 in appropriate brain development and function.

SIGNIFICANCE STATEMENT

As a family, class I TRIM E3 ubiquitin ligases play important roles in neuronal development and function, potentially cooperatively. TRIM67 is the most evolutionarily conserved class I TRIM and is developmentally regulated and brain-enriched. Deletion of murine Trim67 results in malformations of a subset subcortical brain regions and of cortical and subcortical myelinated fiber tracts, as well as deficits in spatial memory, motor function, sociability and sensorimotor gating. We conclude that TRIM67 is critical for appropriate brain development and behavior, potentially downstream of the axon guidance cue netrin, and in cooperation with class I TRIM9.
Narratives of recovery in people with coexisting mental health and alcohol misuse difficulties
Authors: Stott Andrew , Priest Helena
Published: December 2017

Purpose

Existing literature has examined what recovery means to people with co-occurring difficulties, but does little to examine experiences of recovery as a process. The purpose of this paper is to use a narrative approach to explore the process of recovery as an individual journey in a social context. It focuses on people who use alcohol in order to explore the impact of alcohol’s specific cultural meanings on the recovery journey.

Design/methodology/approach

Ten interviews with people with coexisting mental health and alcohol misuse difficulties were conducted, audio-recorded, and transcribed. The transcriptions were analysed using narrative analysis.

Findings

Most participants’ narratives shared a three-part structure, from a traumatic past, through an episode of change, to an ongoing recovery phase. Change and recovery were attributed to several factors including flexible and practical support from services, therapeutic relationships with key professionals, and peer support. Some participants redefined themselves and their alcohol use in relation to ideas of what it is to be “normal”.

Research limitations/implications

The research excluded people who recover outside of services, replicating a shortcoming of much research in this area.

Practical implications

The value placed on professionals having specialised therapeutic skills in working with trauma highlights the need for training in this area. The role for practical and material support underlines the importance of multi-agency working.

Originality/value

The narrative methodology enables the study to draw links between personal stories of recovery and wider social influences, allowing comment on the implications for services. Further, the experiences of people with coexisting mental health and alcohol misuse difficulties have rarely been studied apart from the dual diagnosis population in general, so this paper is able to investigate the specific challenges for this population.
An investigation of cross-cultural social tagging behaviours between Chinese and Americans
Authors: Hu Qian , Lin Xin , Han Shuguang , Li Lei
Published: December 2017

Purpose

The purpose of this paper is to explore different tagging behaviours between Chinese and Americans by analysing the movie tags, and explore the feasibility of applying cultural differences to tag recommendations.

Design/methodology/approach

This paper introduced hypotheses based on several well-established psychological theories and tested them with social tags for the same movies generated by Chinese and Americans. And to prove the utility of the cultural factor consideration, this paper conducted a cross-cultural tag recommendation experiment.

Findings

The results show that compared with Americans, Chinese users tend to add more tags about movies’ background information (e.g. release year) and global contextual characteristics (e.g. genre); they also prefer to add tags about production countries and factual tags, and cultural factors can be applied for recommending more accurate tags.

Research limitations/implications

Other reasons for tagging differences beyond cultural factors have not be explored. Tags for some sample movies in MovieLens might be unstable, as they had been tagged by a small scale of users; as a result, the tags’ type distribution might be influenced.

Practical implications

The results and conclusion of this study will be beneficial for the cross-cultural applications of social tags and mining users’ interests based on tags.

Originality/value

This paper provided a deeper investigation of the cross-cultural effect in people’s social tagging behaviours from cognitive perspective, and an empirical analysis has been performed to explore proper approaches of incorporating cultural differences for tag recommendation.
Experiences of practice-based learning in phenomenographic perspective
Authors: Rovio-Johansson Airi
Published: December 2017

Purpose

The paper aims to examine, within the context of professional practice and learning, how designers collaboratively working in international teams experience practice-based learning and how such occasions contribute to professional development.

Design/methodology/approach

The paper introduces the cooperation project between Tibro Training Centre and Furniture Technology Centre Trust and its workshop context organized as practice-based learning. Participants’ learning context consisted of a mixture of professional practices allowing different logics and different cultures make up an innovative working site. Qualitative analysis of semi-structured interview data suggests that three phenomenographic hierarchical categories constitute the learning process: getting a recognized professional identity; perceiving new elements and expanding knowledge and seeing new aspects of design work and new steps of development in profession.

Findings

Cooperative practice-based learning is understood as social practice in a community of practice, and as continuous changes of the learning object due to that new aspects are discerned by the learners. These categories illustrate how participants’ meaning making and understanding of the learning object were expressed in cooperation as doings and sayings, as translation and as situated activities in a community of practice. Accordingly, it contributed to participants’ professional development in spite of their different professional educations and professional experiences.

Practical implications

More studies of practice-based learning environments in work places are needed that could help societies and companies to advance integrative efforts of new employees and new immigrants into an increasingly diverse globalized labour market.

Originality/value

The results suggest that understanding as well as content structure and meaning making of the learning object are intertwined constituent aspects of practice-based learning.
Instrumental work values and responses to HR practices
Authors: Huo Meng-Long , Boxall Peter
Published: December 2017

Purpose

Grounded in the theory of person-organisation fit, the purpose of this paper is to investigate the extent to which instrumental work values influence the relationship between HR practices and employee well-being (measured by job satisfaction) in a sample of Chinese workers.

Design/methodology/approach

Questionnaire data for this cross-sectional, quantitative study were collected from 371 front-line workers in a Chinese manufacturer. Structural equation modelling was used to test the hypotheses.

Findings

The results show that work instrumentalism significantly reduces the positive effect of training on job satisfaction while boosting the positive effect of remuneration on job satisfaction. In contrast, there is no evidence for an interaction between instrumentalism and employee involvement.

Practical implications

The results imply that the degree to which HR practices are effective in promoting job satisfaction among these Chinese workers depends both on their work-value orientations and on the implications of the particular HR practice. Managers concerned about job satisfaction in China need to consider the impact of work values and the goals of particular HR practices.

Originality/value

China makes an enormously important contribution to world manufacturing output but the authors need a better understanding of how Chinese workers are likely to interpret and respond to HR practices if employee well-being in Chinese enterprises is to be fostered.
Workplace bullying and employee silence
Authors: Rai Arpana , Agarwal Upasna A.
Published: December 2017

Purpose

The purpose of this paper is to examine the effects of workplace bullying on employee silence (defensive, relational, and ineffectual silence), and to test the mediating role of psychological contract violation (PCV) in this relationship and the extent to which the mediation is moderated by workplace friendship.

Design/methodology/approach

Data were collected from 835 full-time Indian managerial employees working in different Indian organizations.

Findings

Results revealed that workplace bullying positively correlated with silence (defensive, relational, and ineffectual silence). The hypothesized moderated mediation condition was supported as results suggest that PCV mediated the bullying-silence relationship and workplace friendship moderated this mediating pathway, i.e. indirect effects of workplace bullying on employee silence via PCV were weaker for employees with high workplace friendship.

Research limitations/implications

A cross-sectional design, use of self-reported questionnaires, and gender-blind perspective to examine bullying are few limitations of this study.

Practical implications

This is the first study examining employee silence in response to workplace bullying and one of the few attempts to examine employees’ passive coping strategies in response to workplace mistreatment. This study is also one of the rare attempts to examine bullying-outcomes relationship in the Indian context.

Social implications

A well-formulated and effectively implemented anti-bullying policy and management support may encourage employees to combat bullying by raising their voices against it.

Originality/value

This is the first study examining employee silence in response to workplace bullying. This study is also one of the rare attempts to examine bullying-outcomes relationship in the Indian context.
Abusive supervision and knowledge sharing: the moderating role of organizational tenure
Authors: Kim Seckyoung Loretta , Son Seung Yeon , Yun Seokhwa
Published: December 2017

Purpose

Drawing on social exchange theory (SET) and conservation of resources (COR) theory, the purpose of this paper is to examine the negative consequence of abusive supervision on knowledge sharing. Further, this paper explores the moderating role of organizational tenure in the relationship between abusive supervision and employees’ knowledge sharing behavior applying sense-making theory.

Design/methodology/approach

The hypotheses were tested using regression analysis across two independent studies conducted in South Korea.

Findings

The authors found evidence that there was a negative relationship between abusive supervision and employees’ knowledge sharing behavior. Furthermore, the aforementioned relationship was strengthened for those with longer organizational tenure.

Originality/value

This research deepens our understanding of the negative consequences of abusive supervision on employees’ knowledge sharing behavior by drawing on SET and COR theory. Through two independent studies, the results demonstrated that employees who receive abusive treatment from their supervisors tend to reduce their knowledge sharing behavior. Furthermore, this detrimental effect is stronger for key knowledge providers, namely long-tenured employees.
Creating a high performing organization in today’s data driven world
Authors: Pozzo Heidi
Published: December 2017

Purpose

The purpose of this paper is to outline what high-performing organizations do to achieve success. In today’s data-driven world, it is easy to get lost in the weeds and not achieve the results you desire. High-performing organizations have figured out how to create focus and leverage resources to achieve outsized results. The paper delves into organizations undergoing transformations and highlights what sets apart those that were successful from those that were not.

Design/methodology/approach

This paper is designed as a viewpoint paper that draws on observations made by the author. Case studies are used to demonstrate the findings and the actions taken that were either successful or not.

Findings

High-performing organizations create focus and leverage resources. The most successful examples have undergone a holistic transformation that was supported by technology.

Originality/value

This paper will provide a roadmap to leaders who want to transform their business into a high-performing organization.
Why people matter far more than digital technology or capital
Authors: Gale Michael , Aarons Chris
Published: December 2017

Purpose

Fifty-five per cent of executives at large corporations are extremely concerned about digital startups becoming significant competitors in their market. If the best technology these startups use is available to everyone and larger companies have the budgets to buy more, how can startups cause such a lack of sleep for leaders? Could the reason be the people, as startups generally are run and staffed by Millennials?

Design/methodology/approach

The evidence for this comes via three separate research efforts and hundreds of hours of intense interviews with transformation leaders in commercial organizations such as USAA, Southwest Airlines, Citi, Hallmark, MIT and government agencies such as the GSA and the FCC. This research looked at how organizations were changing the way they think, organize, invest and act in pursuit of digital transformation success.

Findings

Sixteen per cent of larger organizations saw a real return on their digital transformation efforts. Successful digitally transforming organizations could cut OPEX three times more effectively than other organizations. Successful digitally transforming organizations (56 per cent of them) saw sales performance and customer satisfaction rise in unison. Forty-two per cent of these organizations revealed and solved new digital challenges that they had not recognized before; 87 per cent of these organizations saw enhanced growth in demand.

Originality/value

Technology is a huge part of digital transformation. IDC has predicted that in 2017, $1.7tn will be invested on digital transformation technology and processes alone. That is the size of the tenth largest economy in the world.
Combined electrical stimulation and exercise for swallow rehabilitation post‐stroke: a pilot randomized control trial
Authors: Sproson Lise , Pownall Sue , Enderby Pam , Freeman Jenny
Published: December 2017

Background

Dysphagia is common after stroke, affecting up to 50% of patients initially. It can lead to post‐stroke pneumonia, which causes 30% of stroke‐related deaths, a longer hospital stay and poorer health outcomes. Dysphagia care post‐stroke generally focuses on the management of symptoms, via modified oral intake textures and adapted posture, rather than direct physical rehabilitation of the swallowing function. Transcutaneous neuromuscular electrical stimulation (NMES) is a promising rehabilitation technology that can be used to stimulate swallowing; however, findings regarding efficacy have been conflicting.

Aims

This pilot randomized controlled study involving three UK sites compared the efficacy of the Ampcare Effective Swallowing Protocol (ESP), combining NMES with swallow‐strengthening exercises, with usual care in order to clarify evidence on NMES in the treatment of dysphagia post‐stroke. A further objective was to pilot recruitment procedures and outcome measures in order to inform the design of a full‐scale trial.

Methods & Procedures

Thirty patients were recruited and randomized into either (1) usual speech and language therapy dysphagia care; or (2) Ampcare ESP, receiving treatment 5 days/week for 4 weeks. Outcome measures included: the Functional Oral Intake Scale (FOIS), the Rosenbek Penetration‐Aspiration Scale (PAS) and patient‐reported outcomes (Swallow Related Quality of Life—SWAL‐QOL).

Outcomes & Results

Thirty patients were recruited; 15 were randomized to the Ampcare ESP intervention arm and 15 to usual care. A greater proportion (75%, or 9/12) of patients receiving Ampcare ESP improved compared with 57% (or 8/14) of the usual‐care group. Patients receiving Ampcare ESP also made clinically meaningful change (a comparative benefit of 1.5 on the FOIS, and on the PAS: 1.35 for diet and 0.3 for fluids) compared with usual care. The intervention group also reported much better outcome satisfaction.

Conclusions & Implications

The pilot demonstrated successful recruitment, treatment safety and tolerability and clinically meaningful outcome improvements, justifying progression to a fully powered study. It also showed clinically meaningful treatment trends for the Ampcare ESP intervention.
Development of a Patient Decision Aid for Syncope in the Emergency Department: the SynDA Tool
Authors: Probst Marc A. , Hess Erik P. , Breslin Maggie , Frosch Dominick L. , Sun Benjamin C. , Langan Marie‐Noelle , Richardson Lynne D.
Published: December 2017

Objectives

The objective was to develop a patient decision aid (DA) to promote shared decision making (SDM) for stable, alert patients who present to the emergency department (ED) with syncope.

Methods

Using input from patients, clinicians, and experts in the field of syncope, health care design, and SDM, we created a prototype of a paper‐based DA to engage patients in the disposition decision (admission vs. discharge) after an unremarkable ED evaluation for syncope. In phase 1, we conducted one‐on‐one semistructured exploratory interviews with 10 emergency physicians and 10 ED syncope patients. In phase 2, we conducted one‐on‐one directed interviews with 15 emergency care clinicians, five cardiologists, and 12 ED syncope patients to get detailed feedback on DA content and design. We iteratively modified the aid using feedback from each interviewee until clarity and usability had been optimized.

Results

The 11 × 17‐inch, paper‐based DA, titled SynDA, includes four sections: 1) explanation of syncope, 2) explanation of future risks, 3) personalized 30‐day risk estimate, and 4) disposition options. The personalized risk estimate is calculated using a recently published syncope risk‐stratification tool. This risk estimate is stated in natural frequency and graphically displayed using a 100‐person color‐coded pictogram. Patient‐oriented questions are included to stimulate dialogue between patient and clinician. At the end of the development process, patient and physician participants expressed satisfaction with the clarity and usability of the DA.

Conclusions

We iteratively developed an evidence‐based DA to facilitate SDM for alert syncope patients after an unremarkable ED evaluation. Further testing is required to determine its effects on patient care. This DA has the potential to improve care for syncope patients and promote patient‐centered care in emergency medicine.
The Canadian border and the US dollar: The impact of exchange rate changes on US retailers
Authors: Chen Zhe , Devereux Michael B. , Lapham Beverly
Published: December 2017

This paper provides a micro‐level investigation into the impact of changes in the US–Canada nominal exchange rate on retailers in US regions lying close to the US–Canada border. Using a large data set on product‐level retail prices and sales in the United States over a nine year period, we explore the links between changes in exchange rates, cross‐border travel and the price and quantity responses of US retailers. This allows us to assess the importance of geography and distance in affecting the pass‐through of exchange rate changes into prices and quantities at the level of the consumer. We develop a two‐stage theoretical model of cross‐border travel and industry equilibrium for retail sales at the border. Our empirical results accord well with the implications of the model.
Interleukin‐6/signal transducer and activator of transcription 3 promotes prostate cancer resistance to androgen deprivation therapy via regulating pituitary tumor transforming gene 1 expression
Authors: Huang Shengquan , Liu Qian , Liao Qianjin , Wu Qingjian , Sun Bishao , Yang Zhenxing , Hu Xiaoyan , Tan Mingjia , Li Longkun
Published: December 2017

Prostate cancer can progress from androgen dependence to androgen deprivation resistance with some unknown mechanisms. The current study aims to explore the possible role of pituitary tumor transforming gene1 (PTTG1) in castration‐resistant prostate cancer (CRPC). Initially, we found that PTTG1 expression was significantly increased in androgen‐independent prostate cancer cell lines PC3, DU145 and CRPC specimens compared with that in androgen‐dependent prostate cancer cell line LNCaP and initial prostate cancer specimens. PTTG1 overexpression significantly enhanced the cell survival rate, clonality and tumorigenicity in LNCaP cells upon androgen‐deprivation therapy (ADT). While knockdown of PTTG1 expression significantly elevated the sensitivity of DU145 cells to ADT. The effects of PTTG1 overexpression on LNCaP cells may be ascribed to the induced EMT and increased CD44+CD24‐ cancer stem cell population. Furthermore, we detected that PTTG1 expression was regulated by interleukin‐6 via activated signal transducer and activator of transcription 3 (STAT3) directly binding to the region −500 to +1 of PTTG1 promoter in LNCaP cells. In conclusion, our results elucidate that interleukin‐6/STAT3 activation can increase PTTG1 expression and, consequently, promote the resistance to ADT in CRPC by inducing EMT and increasing the cancer stem cell population, suggesting that PTTG1 may be a novel therapeutic target for CRPC.
An overview on Vadimezan (DMXAA): The vascular disrupting agent
Authors: Daei Farshchi Adli Amir , Jahanban‐Esfahlan Rana , Seidi Khaled , Samandari‐Rad Sonia , Zarghami Nosratollah
Published: December 2017

Vascular disrupting agents (VDAs), a group of cancer remedies, can cause a specific and irreversible destruction of established tumor vessels, and the complete halt of blood flow in the tumor. DMXAA (ASA404) or Vadimezan, a flavone‐acetic acid‐based drug, is the most promising VDAs that induces a rapid shutdown of blood flow in tumors but not in normal tissue. The exact mechanism of vascular disruption is unknown; however, proposed direct and indirect mechanisms of action for DMXAA comprises (i) inducing apoptosis in endothelial cells; (ii) hemorrhagic necrosis and ischemia in tumor; (iii) release of serotonin (5‐HT); (vi) stimulation of innate immune system; (v) production of inflammatory cytokines, for example TNF, IL‐6, GCSF, KC, IP‐10, and MCP‐1; (vi) activation of NFκB and p38 (MAPK); (vii) production of nitric oxide; and (viii) reducing tumor energetics and membrane turnover. Despite the remarkable results from preclinical and phase I/II, DMXAA has failed in phase III clinical trials. The reason for this surprising discrepancy, among others, was discovered to be STING receptor variations between mice and humans. In this review, the development, the mechanisms of DMXAA action, the clinical trials, the combination therapy, and the future of this drug will be discussed.
Priorities for future research into asthma diagnostic tools: A PAN‐EU consensus exercise from the European asthma research innovation partnership (EARIP)
Authors: Garcia‐Marcos L. , Edwards J. , Kennington E. , Aurora P. , Baraldi E. , Carraro S. , Gappa M. , Louis R. , Moreno‐Galdo A. , Peroni D. G. , Pijnenburg M. , Priftis K. N. , Sanchez‐Solis M. , Schuster A. , Walker S. ,   the EARIP Collaboration
Published: December 2017

The diagnosis of asthma is currently based on clinical history, physical examination and lung function, and to date, there are no accurate objective tests either to confirm the diagnosis or to discriminate between different types of asthma. This consensus exercise reviews the state of the art in asthma diagnosis to identify opportunities for future investment based on the likelihood of their successful development, potential for widespread adoption and their perceived impact on asthma patients. Using a two‐stage e‐Delphi process and a summarizing workshop, a group of European asthma experts including health professionals, researchers, people with asthma and industry representatives ranked the potential impact of research investment in each technique or tool for asthma diagnosis and monitoring. After a systematic review of the literature, 21 statements were extracted and were subject of the two‐stage Delphi process. Eleven statements were scored 3 or more and were further discussed and ranked in a face‐to‐face workshop. The three most important diagnostic/predictive tools ranked were as follows: “New biological markers of asthma (eg genomics, proteomics and metabolomics) as a tool for diagnosis and/or monitoring,” “Prediction of future asthma in preschool children with reasonable accuracy” and “Tools to measure volatile organic compounds (VOCs) in exhaled breath.”
Sex‐based differences in CD103+ dendritic cells promote female‐predominant Th2 cytokine production during allergic asthma
Authors: Masuda C. , Miyasaka T. , Kawakami K. , Inokuchi J. , Kawano T. , Dobashi‐Okuyama K. , Takahashi T. , Takayanagi M. , Ohno I.
Published: December 2017

Background

Gender disparities in adult patients with asthma regarding its prevalence and severity are mainly due to enhanced type 2 T‐helper (Th2) cytokine production in female patients compared to that in male patients. However, the pathways mediating this effect remain unclear.

Objective

We aimed to determine the roles of two major subsets of dendritic cells (DCs) in females, specifically those displaying CD11b or CD103, during enhanced Th2 priming after allergen exposure, using an ovalbumin‐induced asthma mouse model.

Methods

Sex‐based differences in the number of DCs at inflamed sites, costimulatory molecule expression on DCs, and the ability of DCs to differentiate naïve CD4+ T cells into Th2 population were evaluated after allergen exposure in asthmatic mice. In addition, we assessed the role of 17β‐oestradiol in CD103+ DC function during Th2 priming in vitro.

Results

The number of CD11bhigh DCs and CD103+ DCs in the lung and bronchial lymph node (BLN) was increased to a greater extent in female mice than in male mice at 16 to 20 hours after ovalbumin (OVA) inhalation. In BLNs, CD86 and I‐A/I‐E expression levels and antigen uptake ability in CD103+ DCs, but not in CD11bhigh DCs, were greater in female mice than in male mice. Furthermore, CD4+ T cells cultured with CD103+ DCs from female mice produced higher levels of interleukin (IL)‐4, IL‐5, and IL‐13, compared with CD4+ T cells cultured with CD103+ DCs from male mice. The 17β‐oestradiol‐oriented enhancement of CD86 expression on CD103+ DCs after allergen exposure induced the enhanced IL‐5 production from CD4+ T cells.

Conclusions and Clinical Relevance

These findings suggest that with regard to asthma, enhanced Th2 cytokine production in females might be attributed to 17β‐oestradiol‐mediated Th2‐oriented CD103+ DCs in the BLN.
Luteinizing hormone and insulin resistance in menopausal patients with adrenal incidentalomas: The cause‐effect relationship?
Authors: Marina Ljiljana V. , Ivović Miomira , Tančić‐Gajić Milina , Arizanović Zorana , Raković Dragana , Milin‐Lazović Jelena , Kendereški Aleksandra , Micić Dragan , Vujović Svetlana
Published: December 2017

Objective

A high prevalence of insulin resistance (IR) has proven to manifest in patients with adrenal incidentalomas (AI). It has been demonstrated that an increase in IR is related to the size of tumourous masses; additionally, luteinizing hormone (LH)‐dependent adrenal pathologies are well documented in patients with LH‐responsive adrenal tumours occurring under conditions of physiologically elevated LH. We hypothesized that an association between LH and insulin might play a role in adrenal tumourigenesis and steroidogenesis.

Design

The aim of our study was to investigate the association between LH and IR; adrenal tumour size (ATS) and IR; LH and cortisol after the 1 mg overnight dexamethasone test (1 mg DST); and ATS and 1 mg DST cortisol in AI patients. This was a case‐control study conducted in the Clinic for Endocrinology, Diabetes and Metabolic Diseases in Belgrade, Serbia. The total study group consisted of 105 menopausal women: 75 AI patients [27 with nonfunctional AI (NAI) and 48 with (possible) autonomous cortisol secretion ((P)ACS)] and 30 age‐, BMI‐, LH‐ and menopause duration‐matched healthy control (HC) women. To estimate IR, we used homeostasis model assessment (HOMA‐IR).

Results

Luteinizing hormone and ATS are in a significant positive correlation with HOMA‐IR and 1 mg DST cortisol in menopausal patients with AI and (P)ACS.

Conclusions

Our data point to a possible cause‐effect relationship between LH and insulin in patients with AI and (P)ACS adding to the body of evidence of their involvement in adrenal tumourigenesis and steroidogenesis.
The effect of flurbiprofen oral spray and ibuprofen vs ibuprofen alone on postoperative tonsillectomy pain: An open, randomised, controlled trial
Authors: Türk B. , Akpınar M. , Erol Z.N. , Kaya K.S. , Ünsal Ö. , Coşkun B.U.
Published: December 2017

Objective

This prospective clinical study was carried out to evaluate the analgesic efficacy and safety of oral spray form of flurbiprofen in the treatment of postoperative pain in tonsillectomy patients.

Study design

Open, randomised, controlled clinical study.

Setting

Tertiary care training and research hospital.

Participants

One hundred (53 males, 47 females) with an age range of 18‐53 years old (mean 27.4 ± 9.3 SD) undergoing tonsillectomy were enrolled in this prospective controlled study.

Main outcome measures

Patients receiving oral ibuprofen and flurbiprofen as spray form were enrolled as study group (53), whereas patients receiving only oral ibuprofen were enrolled as control group (47) in postoperative period. Postoperative pain was evaluated through visual analogue scale on 12th hour, first, third and seventh days after surgery.

Results

The mean maximal pain score of patients who have received flurbiprofen spray and ibuprofen was 3.36 ± 1.93 SD that was statistically lower than the mean maximal pain score of patients who were medicated with only ibuprofen which was 4.06 ± 1.29 SD on postoperative seventh day (P = .013).

Conclusion

This study revealed that addition of flurbiprofen spray to oral ibuprofen is effective in the management of postoperative pain in tonsillectomy patients with no notable complications.
CHA2DS2‐VASc scores for outcome prediction in acute ischaemic stroke
Authors: Su Chun‐Hung , Tsao Teng‐Fu , Chen An‐Chih , Chang Kai‐Wei , Yang Yi‐Sun , Ueng Kwo‐Chang , Tsai Chin‐Feng
Published: December 2017

Background

The CHADS2 and CHA2DS2‐VASc scores are clinical risk stratification instruments that are used clinically to assess the risk of stroke in patients with atrial fibrillation (AF). The aim of this study was to evaluate whether the prestroke CHADS2 and CHA2DS2‐VASc scores could be useful for predicting infarction severity and long‐term outcomes in patients with acute ischaemic stroke.

Materials and methods

This prospective study included all 1494 patients who had acute ischaemic stroke without haemorrhagic transformation which was evidenced with magnetic resonance (MR) imaging during hospitalization. Total infarction volume and arterial stenosis score were calculated based on MR imaging. National Institutes of Health Stroke Scale scores (NIHSSs) were obtained at admission and discharge by board‐certified neurologists. The clinical outcomes were defined as composite endpoints of restroke and mortality and were recorded with the mean follow‐up period of 37.5 months.

Results

There were 195 (13.1%) patients with AF. The patients with AF had significantly higher median CHADS2 and CHA2DS2‐VASc scores than the patients without AF (P < .001). Patients with higher CHADS2 and CHA2DS2‐VASc scores had significantly higher total infarction volume, arterial stenosis score and NIHSS scores at discharge and poorer clinical outcomes. After adjusting for age, gender and AF, only CHA2DS2‐VASc scores could predict both restroke and composite endpoints.

Conclusions

Prestroke CHA2DS2‐VASc scores appear to have better clinical value for predicting the severity of infarction and long‐term clinical outcomes in acute ischaemic stroke patients with and without AF.
Association between hemorrhagic transformation after endovascular therapy and poststroke seizures
Authors: Thevathasan Arthur , Naylor Jillian , Churilov Leonid , Mitchell Peter J. , Dowling Richard J. , Yan Bernard , Kwan Patrick
Published: December 2017

Objective

Endovascular therapy has recently become standard therapy for select patients with acute ischemic stroke. Infarcted brain tissue may undergo hemorrhagic transformation (HT) after endovascular therapy. We investigated the association between HT and occurrence of poststroke seizures in patients treated with endovascular therapy.

Methods

Consecutive patients treated with endovascular therapy for acute anterior circulation ischemic stroke were included. HT was assessed with computed tomography/magnetic resonance imaging (CT/MRI) at 24 h after stroke onset. Patients were followed for up to 2 years for seizure occurrence.

Results

A total of 205 (57.1% male) patients were analyzed. Median age was 69 years (interquartile range [IQR] 57‐78). Among patients with HT, 17.9% (10/56) developed poststroke seizures compared with 4.0% (6/149) among those without HT (hazard ratio [HR] 5.52; 95% confidence interval [CI] 2.00‐15.22; P = .001). The association remained significant after adjustment for cortical involvement, baseline National Institutes of Health Stroke Scale score, age and use of intravenous tissue plasminogen activator and clot retrieval (HR 4.85; 95% CI 1.60‐14.76; P = .005). In patients who developed seizures within the follow‐up period, median time to first seizure was 111 days (IQR 28‐369) in patients with HT and 36 days (IQR 0.5‐183) in patients without HT.

Significance

A patient who develops HT following endovascular therapy for acute ischemic stroke had a nearly 5 times higher rate of developing poststroke seizures within 2 years. HT may be used as an imaging biomarker for poststroke seizures.
Sorrow and cardiovascular events
Authors: Mazokopakis E. E.
Published: December 2017

Click here to view the Letter to the Editor by C. Hagström & C. Held
Rates of gut microbiome divergence in mammals
Authors: Nishida Alex H. , Ochman Howard
Published: December 2017

The variation and taxonomic diversity among mammalian gut microbiomes raises several questions about the factors that contribute to the rates and patterns of change in these microbial communities. By comparing the microbiome compositions of 112 species representing 14 mammalian orders, we assessed how host and ecological factors contribute to microbiome diversification. Except in rare cases, the same bacterial phyla predominate in mammalian gut microbiomes, and there has been some convergence of microbiome compositions according to dietary category across all mammalians lineages except Chiropterans (bats), which possess high proportions of Proteobacteria and tend to be most similar to one another regardless of diet. At lower taxonomic ranks (families, genera, 97% OTUs), bacteria are more likely to be associated with a particular mammalian lineage than with a particular dietary category, resulting in a strong phylogenetic signal in the degree to which microbiomes diverge. Despite different physiologies, the gut microbiomes of several mammalian lineages have diverged at roughly the same rate over the past 75 million years; however, the gut microbiomes of Cetartiodactyla (ruminants, whales, hippopotami) have evolved much faster and those of Chiropterans much slower. Contrary to expectations, the number of dietary transitions within a lineage does not influence rates of microbiome divergence, but instead, some of the most dramatic changes are associated with the loss of bacterial taxa, such as those accompanying the transition from terrestrial to marine lifestyles and the evolution of hominids.
Agriculture shapes the trophic niche of a bat preying on multiple pest arthropods across Europe: Evidence from DNA metabarcoding
Authors: Aizpurua Ostaizka , Budinski Ivana , Georgiakakis Panagiotis , Gopalakrishnan Shyam , Ibañez Carlos , Mata Vanessa , Rebelo Hugo , Russo Danilo , Szodoray‐Parádi Farkas , Zhelyazkova Violeta , Zrncic Vida , Gilbert M. Thomas P. , Alberdi Antton
Published: December 2017

The interaction between agricultural production and wildlife can shape, and even condition, the functioning of both systems. In this study, we i) explored the degree to which a widespread European bat, namely the common bent‐wing bat Miniopterus schreibersii, consumes crop‐damaging insects at a continental scale, and ii) tested whether its dietary niche is shaped by the extension and type of agricultural fields. We employed a dual‐primer DNA metabarcoding approach to characterize arthropod 16S and COI DNA sequences within bat faecal pellets collected across 16 Southern European localities, to first characterize the bat species’ dietary niche, second measure the incidence of agricultural pests across their ranges and third assess whether geographical dietary variation responds to climatic, landscape diversity, agriculture type and vegetation productivity factors. We detected 12 arthropod orders, among which lepidopterans were predominant. We identified >200 species, 44 of which are known to cause agricultural damage. Pest species were detected at all but one sampling site and in 94% of the analysed samples. Furthermore, the dietary diversity of M. schreibersii exhibited a negative linear relation with the area of intensive agricultural fields, thus suggesting crops restrict the dietary niche of bats to prey taxa associated with agricultural production within their foraging range. Overall, our results imply that M. schreibersii might be a valuable asset for biological pest suppression in a variety of agricultural productions and highlight the dynamic interplay between wildlife and agricultural systems.
Mechanisms of thermal adaptation and evolutionary potential of conspecific populations to changing environments
Authors: Chen Zhongqi , Farrell Anthony P. , Matala Amanda , Narum Shawn R.
Published: December 2017

Heterogeneous and ever‐changing thermal environments drive the evolution of populations and species, especially when extreme conditions increase selection pressure for traits influencing fitness. However, projections of biological diversity under scenarios of climate change rarely consider evolutionary adaptive potential of natural species. In this study, we tested for mechanistic evidence of evolutionary thermal adaptation among ecologically divergent redband trout populations (Oncorhynchus mykiss gairdneri) in cardiorespiratory function, cellular response and genomic variation. In a common garden environment, fish from an extreme desert climate had significantly higher critical thermal maximum (p < .05) and broader optimum thermal window for aerobic scope (>3°C) than fish from cooler montane climate. In addition, the desert population had the highest maximum heart rate during warming (20% greater than montane populations), indicating improved capacity to deliver oxygen to internal tissues. In response to acute heat stress, distinct sets of cardiac genes were induced among ecotypes, which helps to explain the differences in cardiorespiratory function. Candidate genomic markers and genes underlying these physiological adaptations were also pinpointed, such as genes involved in stress response and metabolic activity (hsp40,ldh‐bandcamkk2). These markers were developed into a multivariate model that not only accurately predicted critical thermal maxima, but also evolutionary limit of thermal adaptation in these specific redband trout populations relative to the expected limit for the species. This study demonstrates mechanisms and limitations of an aquatic species to evolve under changing environments that can be incorporated into advanced models to predict ecological consequences of climate change for natural organisms.
A candidate tolerance gene identified in a natural population of field voles (Microtus agrestis)
Authors: Wanelik Klara M. , Begon Michael , Birtles Richard J. , Bradley Janette E. , Friberg Ida M. , Jackson Joseph A. , Taylor Christopher H. , Thomason Anna G. , Turner Andrew K. , Paterson Steve
Published: December 2017

The animal immune response has hitherto been viewed primarily in the context of resistance only. However, individuals can also employ a tolerance strategy to maintain good health in the face of ongoing infection. To shed light on the genetic and physiological basis of tolerance, we use a natural population of field voles,Microtus agrestis, to search for an association between the expression of the transcription factor Gata3, previously identified as a marker of tolerance in this system, and polymorphism in 84 immune and nonimmune genes. Our results show clear evidence for an association between Gata3 expression and polymorphism in the Fcer1a gene, with the explanatory power of this polymorphism being comparable to that of other nongenetic variables previously identified as important predictors of Gata3 expression. We also uncover the possible mechanism behind this association using an existing protein–protein interaction network for the mouse model rodent,Mus musculus, which we validate using our own expression network forM. agrestis. Our results suggest that the polymorphism in question may be working at the transcriptional level, leading to changes in the expression of the Th2‐related genes, Tyrosine‐protein kinaseBTKand Tyrosine‐protein kinaseTXK, and hence potentially altering the strength of the Th2 response, of which Gata3 is a mediator. We believe our work has implications for both treatment and control of infectious disease.