bluuebunny/crossref_metadata_2025 huggingface dataset:
Automated High-Throughput Light-Sheet Fluorescence Microscopy of Larval Zebrafish
Authors: Logan Savannah L. , Dudley Christopher , Baker Ryan P. , Taormina Michael J. , Hay Edouard A. , Parthasarathy Raghuveer
Published: May 2018

ABSTRACT

Light sheet fluorescence microscopy enables fast, minimally phototoxic, three-dimensional imaging of live specimens, but is currently limited by low throughput and tedious sample preparation. Here, we describe an automated high-throughput light sheet fluorescence microscope in which specimens are positioned by and imaged within a fluidic system integrated with the sheet excitation and detection optics. We demonstrate the ability of the instrument to rapidly examine live specimens with minimal manual intervention by imaging fluorescent neutrophils over a nearly 0.3 mm3 volume in dozens of larval zebrafish. In addition to revealing considerable inter-individual variability in neutrophil number, known previously from labor-intensive methods, three-dimensional imaging allows assessment of the correlation between the bulk measure of total cellular fluorescence and the spatially resolved measure of actual neutrophil number per animal. We suggest that our simple experimental design should considerably expand the scope and impact of light sheet imaging in the life sciences.
Structural investigation of one- and two-dimensional coordination polymers based on cobalt–bis(dioxolene) units and 1-hydroxy-1,2,4,5-tetrakis(pyridin-4-yl)cyclohexane
Authors: Drath Olga , Gable Robert W. , Boskovic Colette
Published: May 2018

The combination of cobalt, 3,5-di-tert-butyldioxolene (3,5-dbdiox) and 1-hydroxy-1,2,4,5-tetrakis(pyridin-4-yl)cyclohexane (tpch) yields two coordination polymers with different connectivities, i.e. a one-dimensional zigzag chain and a two-dimensional sheet. Poly[[bis(3,5-di-tert-butylbenzene-1,2-diolato)bis(1,5-di-tert-butyl-4-oxocyclohexa-2,5-dien-1-yl-3-olato)[μ4-1-hydroxy-1,2,4,5-tetrakis(pyridin-4-yl)cyclohexane]cobalt(III)]–ethanol–water 1/7/5], {[Co2(C14H20O2)4(C26H24N4O)]·7C2H5OH·5H2O}
n
or {[Co2(3,5-dbdiox)4(tpch)}·7EtOH·5H2O}
n
, is the second structurally characterized example of a two-dimensional coordination polymer based on linked {Co(3,5-dbdiox)2} units. Variable-temperature single-crystal X-ray diffraction studies suggest that catena-poly[[[(3,5-di-tert-butylbenzene-1,2-diolato)(1,5-di-tert-butyl-4-oxocyclohexa-2,5-dien-1-yl-3-olato)cobalt(III)]-μ-1-hydroxy-1,2,4,5-tetrakis(pyridin-4-yl)cyclohexane]–ethanol–water (1/1/5)], {[Co(C14H20O2)2(C26H24N4O)]·C2H5OH·5H2O}
n
or {[Co(3,5-dbdiox)2(tpch)]·EtOH·5H2O}
n
, undergoes a temperature-induced valence tautomeric interconversion.
Can I have more of these please?
Authors: Sesagiri Raamkumar Aravind , Foo Schubert , Pang Natalie
Published: May 2018

Purpose

During the literature review phase, the task of finding similar research papers can be a difficult proposition for researchers due to the procedural complexity of the task. Current systems and approaches help in finding similar papers for a given paper, even though researchers tend to additionally search using a set of papers. This paper aims to focus on conceptualizing and developing recommendation techniques for key literature review and manuscript preparatory tasks that are interconnected. In this paper, the user evaluation results of the task where seed basket-based discovery of papers is performed are presented.

Design/methodology/approach

A user evaluation study was conducted on a corpus of papers extracted from the ACM Digital Library. Participants in the study included 121 researchers who had experience in authoring research papers. Participants, split into students and staff groups, had to select one of the provided 43 topics and run the tasks offered by the developed assistive system. A questionnaire was provided at the end of each task for evaluating the task performance.

Findings

The results show that the student group evaluated the task more favourably than the staff group, even though the difference was statistically significant for only 5 of the 16 measures. The measures topical relevance, interdisciplinarity, familiarity and usefulness were found to be significant predictors for user satisfaction in this task. A majority of the participants, who explicitly stated the need for assistance in finding similar papers, were satisfied with the recommended papers in the study.

Originality/value

The current research helps in bridging the gap between novices and experts in terms of literature review skills. The hybrid recommendation technique evaluated in this study highlights the effectiveness of combining the results of different approaches in finding similar papers.
Institutional repositories: a bibliometric study of the social sciences citation index (SSCI)
Authors: Liao Yi-Ping , Ma Tsu-Jui
Published: May 2018

Purpose

This paper aims to provide a bibliometric study of journal articles related to institutional repositories in the Social Sciences Citation Index (SSCI) between January 1993 and August 2017. This study will provide researchers with a foundation for further research.

Design/methodology/approach

In this study, articles published were analyzed; titles were searched using the term “institutional repositories.” The data were evaluated in response to four research questions on the following topics: publication trends, prolific authors, core journals and times cited.

Findings

The results indicate that 124 articles on institutional repositories were authored by 223 individuals. These articles were cited 722 times in 37 journals, and the h-index provided by the Web of Science was 14.

Research limitations/implications

This study only investigated articles titled with institutional repositories in the SSCI. Other items were not included.

Practical implications

This study shows that the implementation of institutional repositories has been limited to library and information science. If they can be used broadly in different disciplines, a better outcome can be expected.

Social implications

Based on the findings, the growth of institutional repositories as an academic subject is likely to continue. If such discussions can be conducted in other disciplines, institutional repositories may be able to provide a more promising outcome to academia.

Originality/value

This paper is valuable for researchers who wish to examine the trends of institutional repositories in the SSCI and seek possible areas for further research.
Developing a service value measurement scale in retail banking services
Authors: Roy Sanjit Kumar , Paul Rik , Quazi Ali , Nguyen Bang
Published: May 2018

Purpose

The purpose of this paper is to develop and validate a scale for measuring consumers’ perceived service value in the Indian retail banking services. This purpose is rooted in the absence of consensus on what constitutes service value and how to measure such value in the above context.

Design/methodology/approach

The scale development procedure comprised qualitative and quantitative approaches. A list of possible measurement items was compiled based on literature review and expert opinion through focus groups. Data were collected from a sample of 442 respondents representing the Indian retail banking sector using survey instrument and were analyzed using the structural equation modeling.

Findings

The study revealed a seven-dimensional scale for measuring service which includes service equity, service quality, customer intimacy, product leadership, operational effectiveness, customer communication, and perceived sacrifice. Thus, the scale emerging from this study is consistent with established scales and is applicable to the Indian retail services setting. This study contributes to the knowledge gap by confirming that the west-centric service value measurement scale is moderately applicable to the services sector in India.

Originality/value

This research is a direct response to calls from the leading marketing pundits to explore the validity and applicability of the existing marketing constructs and models originated in the west to Indian markets. Keeping in mind the established service value measurement scale, this study develops and validates a seven-dimensional scale for measuring service value in an Indian setting with novel sub-dimensions.
Multi-level mentoring practices in a Teacher Education Program in Greece
Authors: Brinia Vasiliki , Psoni Paraskevi
Published: May 2018

Purpose

The purpose of this paper is to reflect the multi-level mentoring practices of a Teacher Education Program in Greece and the mentors’ perceptions on them. The mentoring practices of the specific Program are unique in Teacher Education in Greece; and therefore, the paper examines the extent to which they are considered as capable of developing in mentors and mentees specific skills that contribute to the development of student-teachers’ professional identity.

Design/methodology/approach

The case study is based on qualitative research and 32 interviews with mentors of the specific Program who report their experience. Six mentees have also been asked to provide the researchers with comments, so as to observe whether their answers confirm the mentors’ perceptions.

Findings

The different types of mentoring of the specific Program are perceived as able to enhance the mentors’ and the mentees’ professional development and self-confidence as well as to the latters’ improved transition and engagement to the Program. The authors also contribute to the fostering of the mentees’ experiential learning and to the capitalization of knowledge in Teacher Education. The EES teacher mentoring is considered of important adding value to the formation of student-teachers’ professional identity, according to the mentors interviewed. Mentees comments were found to confirm the mentors’ perceptions.

Originality/value

The conclusions of the paper are of significant value, since multi-level mentoring as a holistic approach to teacher-candidates’ experiential learning and professional development examined in a single paper is rather rare. Moreover, the Program of the paper’s case study follows this multi-level innovative approach, which includes EES teacher mentoring, and which is of considerable adding value, according to the mentors and the mentees interviewed. It could, therefore, constitute a paradigm for other Teacher Education Programs in Greece and in other countries.
Regulatory non-compliance and performance of deposit money banks in Nigeria
Authors: Yusuf Ismaila , Ekundayo Damola
Published: May 2018

Purpose

The purpose of this study is to examine regulatory sanctions from an emerging economy perspective and analyzing the impact of regulators imposed monetary sanctions on banks’ performance.

Design/methodology/approach

The study adopted correlational research design to examine the effect of regulatory penalties on the performance of deposit money banks in Nigeria. This study used panel data from a sample of 15 deposit money banks in Nigeria for the period of 2006-2015. Multiple regression analysis was carried out.

Findings

Results showed that penalties imposed by regulators in the Nigerian banking industry have no significant impact on the bottom line of the defaulters. Penalties imposed on foreign exchange and international trade related infraction showed that the cost of penalties is below the benefits enjoyed from such infractions.

Practical implications

The insignificant impact of penalties on performance implies that deposit money banks have considered penalties imposed by regulators as operational expenses and transferred such to customers.

Originality/value

The study differs from other studies that examined regulatory penalties on performance by focusing on financial performance and using data from an emerging economy perceived to have weak regulatory environment.
A review of credit scoring research in the age of Big Data
Authors: Onay Ceylan , Öztürk Elif
Published: May 2018

Purpose

This paper aims to survey the credit scoring literature in the past 41 years (1976-2017) and presents a research agenda that addresses the challenges and opportunities Big Data bring to credit scoring.

Design/methodology/approach

Content analysis methodology is used to analyze 258 peer-reviewed academic papers from 147 journals from two comprehensive academic research databases to identify their research themes and detect trends and changes in the credit scoring literature according to content characteristics.

Findings

The authors find that credit scoring is going through a quantitative transformation, where data-centric underwriting approaches, usage of non-traditional data sources in credit scoring and their regulatory aspects are the up-coming avenues for further research.

Practical implications

The paper’s findings highlight the perils and benefits of using Big Data in credit scoring algorithms for corporates, governments and non-profit actors who develop and use new technologies in credit scoring.

Originality/value

This paper presents greater insight on how Big Data challenges traditional credit scoring models and addresses the need to develop new credit models that identify new and secure data sources and convert them to useful insights that are in compliance with regulations.
Does corporate social responsibility extend firm life-cycles?
Authors: Hsu Feng Jui
Published: May 2018

Purpose

The purpose of this paper is to assess US-based firms from 2005 to 2015 to determine whether firms with better corporate social responsibility (CSR) performance will allocate capital through their life-cycle to better maintain or extend total assets.

Design/methodology/approach

Kinder, Lydenberg, Domini Research & Analytics social performance rating scores were used to measure CSR performance in an initial sample of 19,707 firm-year observations. Firms are first classified into stages including introduction, growth, maturity, and decline, and use multiclass linear discriminant analysis, the Dickinson classification scheme (Dickinson, 2011), and the ratio of retained earnings to total assets (RETA) as life-cycle proxies. Life-cycle was formulated based on a broad set of accounting data sourced from Compustat. Various corporate characteristics from the CRSP database were used to classify all sample firms into five equal groups based on their CSR performance.

Findings

A firm’s equity and debt issuance assume a hump shape over the life-cycle under CSR practice, and higher-CSR firms face fewer significant issues as they mature; payout, RETA, and free cash flow decreased from high-CSR performance firms to low-CSR performance firms; and cash holdings also exhibit a hump shape over the life-cycle and higher-CSR practices are associated with significantly lower cash holdings.

Originality/value

CSR performance is a useful predictor for forecasting firm life-cycle and superior CSR performance ensures efficient capital allocation throughout firm life-cycle. Furthermore, CSR practice is an indicator of firm life-cycle sustainability and indicates a firm’s future cash flow patterns.
Factors affecting temporary labour migration for seasonal work: a review
Authors: Panda Shilpi Smita , Mishra Nihar Ranjan
Published: May 2018

Purpose

Seasonal labour migration is a common form of temporary migration where the work of the migrant labour depends on seasonal conditions and is performed only during that period of year. This paper aims to identify the factors and subfactors of temporary labour migration from the existing literature.

Design/methodology/approach

The paper is based on an extensive review of the literature on temporary labour migration. Studies done from 1990 to 2016 were considered for review. The literatures from research articles, book chapters, working papers, conference papers and field-based project reports from various disciplines, like economics, sociology, anthropology, psychology and management studies were reviewed for critically analysing various factors affecting seasonal labour migration.

Findings

A total of five key factors and 60 subfactors of temporary labour migration were documented from previous studies. The findings of the study are organized under five thematic segments: economic factors, social factors, environmental factors, policy-related factors and psychological factors New aspects of seasonal migration were identified such as “role of labour contractors ”, “inter-generational mobility”, “social networks”, “grassroot politics”, “migrant’s relationship with the agents”, “labour registration process”, “market intervention” and “civil society intervention” after consultation with the subject experts and field study.

Research limitations/implications

The paper restricts itself to include aspects of temporary labour migration. Only the factors and subfactors affecting temporary migration are taken into purview. Further the findings of the paper can be empirically tested to know the significance of each factor and subfactor.

Practical implications

The paper has implications for better understanding of the temporary labour migration process in different context by focussing extensively on the factors of migration. The factors identified can be empirically tested in regional and local context, which would provide effective insights for policy formulation for the welfare and protection of the migrant workers.

Originality/value

The paper fulfils an identified need to provide a holistic review for understanding and documenting various factors and subfactors that affect the process of temporary labour migration.
An examination of the importance of big data analytics in supply chain agility development
Authors: Mandal Santanu
Published: May 2018

Purpose

This paper aims to investigate the influence of big data analytics (BDA) personnel expertise capabilities in the development of supply chain (SC) agility. Based on extant literature, the study explores the role of BDA technical knowledge, BDA technology management knowledge, BDA business knowledge and BDA relational knowledge in SC agility development. Furthermore, the author also explores the inter-relationships among these four BDA personnel expertise capabilities.

Design/methodology/approach

An expert team consisting of IT practitioners (with a minimum experience of five years) were chosen to comment and modify the established scale items of the constructs used in the study. Subsequently, the measures were further pre-tested with 61 students specializing in computer science and information technology. The final survey was mailed to 651 IT professionals with a minimum experience of five years or more in an allied field. Repeated follow-ups and reminders resulted in 176 completed responses. The responses were analysed using partial least squares in SmartPLS 2.0.M3.

Findings

Findings suggested that BDA technology management knowledge, BDA business knowledge and BDA relational knowledge are prominent enablers of SC agility. Furthermore, BDA technology management knowledge is an essential precursor of BDA technical knowledge and BDA business knowledge.

Originality/value

The study is the foremost in addressing the importance of BDA personnel expertise capabilities in the development of SC agility. Furthermore, it is also the foremost in exploring the inter-relationships among the BDA personnel expertise capabilities.
Functional diversity literacy
Authors: Pionke JJ
Published: May 2018

Purpose

The purpose of this paper is to discuss the problematic nature of librarian attitudes toward people with disabilities and how a language change to the use of the term “functionally diverse” can highlight a greater sense of inclusion and equality, as well as develop a new type of literacy that focuses on understanding and awareness of disabilities, accessibility and difference.

Design/methodology/approach

This paper examines current trends of language use about people with disabilities and then posits a counterpoint by discussing functional diversity as a viable alternative in not just language but also literacy.

Findings

Examples of current problematic language by librarians are drawn from social media and the literature. The examples are deconstructed in regard to why they are problematically exclusive, and then the alternative language of functional diversity is examined as a way to be more inclusive. Developing a new literacy in terms of interaction with functionally diverse people is also discussed.

Originality/value

Library literature on disability largely focuses on a case study approach and on the view of how to assist people with single disabilities. This is one of the very few papers that focuses on discussing the underlying attitudes and assumptions of librarians that make outreach to people with disabilities who use libraries, difficult. This is also one of the few papers that discusses the need for a new type of literacy within librarianship.
Key component of inflammasome, NLRC4, was identified in the lesional epidermis of psoriatic patients
Authors: Hiruma Junichiro , Harada Kazutoshi , Motoyama Akira , Okubo Yukari , Maeda Tatsuo , Yamamoto Mami , Miyai Masashi , Hibino Toshihiko , Tsuboi Ryoji
Published: May 2018

Inflammasomes are multimolecular complexes that control the inflammatory response. The function of inflammasomes in the pathogenesis of psoriasis is still unclear. To clarify the relationship between inflammasomes and the pathophysiology of psoriasis, and in particular, to identify molecules interacting with caspase‐1, a crucial component of inflammasomes, scale extracts obtained from patients with psoriasis were immunoprecipitated with anti‐caspase‐1 antibody and analyzed by liquid chromatography coupled with electrospray tandem mass spectrometry (LC‐MS/MS). The expression of the inflammasome component was assessed by immunohistochemical analysis and an in vitro assay. We identified several candidates for caspase‐1‐interacting proteins from the psoriatic scale extracts by immunoprecipitation and LC‐MS/MS. Nucleotide‐binding oligomerization domain‐containing protein‐like receptor family CARD domain‐containing protein 4 (NLRC4) was the only inflammasome component among the candidates; thus, the protein is considered to be a key factor of inflammasomes in psoriasis. No inflammasome component was found in the extracts of atopic dermatitis or normal skin by LC‐MS/MS. Immunohistochemical analysis demonstrated upregulation of NLRC4 in the lesional epidermis of some psoriatic patients whereas weak expression of NLRC4 was detected in the normal and non‐lesional epidermis. The mRNA expression of the NLRC4 gene increased in keratinocytes at confluency, 48 h after air exposure and after the addition of 1.5 mmol/L calcium chloride. Our findings suggest that NLRC4 may be involved in the exacerbation or modification of psoriatic lesions.
Four cases of acute infectious urticaria showing significant elevation of plasma D‐dimer level
Authors: Takahashi Toshifumi , Minami Shino , Teramura Kazuya , Tanaka Toshihiro , Fujimoto Noriki
Published: May 2018

D‐dimer, a fibrinolytic end‐product, has been regarded as a biomarker indicating the severity of urticaria, especially in chronic urticaria. Regarding acute urticaria, D‐dimer level is also suggested to be elevated, which may be significant in comparison with chronic urticaria. However, the clinical features of acute urticaria with concomitant significant elevation of D‐dimer level have not been investigated in detail so far. We present four cases of acute urticaria fulfilling the proposed diagnostic criterion of acute infectious urticaria, in which significant elevation of D‐dimer level and rapid spontaneous normalization in parallel with the resolution of fever and urticaria occurs. No cases had deep vein thrombosis, disseminated intravascular coagulation and malignancy. All cases responded well to antihistaminic treatment in combination with antibiotics, and their fever and urticaria resolved within 10 days. All cases showed severe wheals persistent for several days resolving with hyperpigmentation. Histologically, infiltration into blood vessel walls and interstitial infiltration of lymphocytes and polymorphonuclear cells were marked in the dermis. In our cases, clinical features accorded with acute infectious urticaria, and their histological features were similar to those of neutrophilic urticaria as described previously. In conclusion, there is a certain group of acute urticaria associated with significant elevation of D‐dimer level. These common features of our cases may be characteristic in acute urticaria showing the coagulative and fibrinolytic abnormalities.
Grass competition overwhelms effects of herbivores and precipitation on early tree establishment in Serengeti
Authors: Morrison Thomas A. , Holdo Ricardo M. , Rugemalila Deusdedith M. , Nzunda Mawazo , Anderson T. Michael
Published: May 2018

Savanna ecosystems span a diverse range of climates, edaphic conditions, and disturbance regimes, the complexity of which has stimulated long‐standing interest in the mechanisms that maintain tree–grass coexistence. One hypothesis suggests that tree establishment is strongly limited by one or several demographic bottlenecks at early stages of the tree life cycle. A major impediment to testing this hypothesis is the lack of data on the relative strengths of different bottlenecks across key environmental gradients.

To identify demographic bottlenecks that limit early tree establishment (0–18 months), we conducted a series of transplant experiments with two savanna trees species (Acacia robusta and Acacia tortilis) across a natural rainfall and soil fertility gradient in the Serengeti ecosystem, Tanzania. We tested the interactive effects of precipitation, herbivory, seed scarification, grass competition, water limitation, and tree species identity on two key life stages: germination and early seedling survival (0–2 months), and juvenile seedling survival (2–18 months).

Germination and early seedling survival increased as a function of rainfall, in the absence of herbivores and when seeds were scarified. Juvenile seedling survival, in contrast, decreased with rainfall but increased in the absence of herbivores. Grass removal had the single strongest (positive) effect on juvenile seedling survival of any treatment. Soil moisture monitoring and grass‐addition treatments revealed that grasses negatively affected seedlings in ways that were not necessarily linked to soil moisture.

A demographic model combining all effects across early life stages showed that the strength of grass competition on juvenile seedling survival was the key factor limiting early tree establishment. While rainfall had an unexpected opposing effect on the two life stages, the net effect of mean annual precipitation on early tree establishment was positive.

Synthesis. Successful tree establishment in Serengeti is maximized by a seemingly unlikely sequence of events: (a) scarification of seeds by browsers, (b) heavy rainfall to promote germination, (c) intensive grazing (but absence of browsers), and (d) dry conditions during juvenile seedling growth (>2 months) to reduce competition with grasses. By considering a wide suite of conditions and their interactions, our experimental results are relevant to ongoing debates about savanna vegetation dynamics and structural shifts in tree:grass ratios.
Analysis of predictors of pain response in patients with bone metastasis undergoing palliative radiotherapy: Does age matter?
Authors: Cacicedo Jon , Gómez‐Iturriaga Alfonso , Navarro Arturo , Morillo Virginia , Willisch Patricia , Lopez‐Guerra Jose Luis , Illescas Ana , Casquero Francisco , Del Hoyo Olga , Ciervide Raquel , Martinez‐Indart Lorea , Bilbao Pedro , Rades Dirk
Published: May 2018

Introduction

To evaluate whether age is a predictor of pain response after radiotherapy for painful bone metastasis (BM).

Methods

Between June 2010 and June 2014, 204 patients with BM undergoing palliative radiotherapy participated in a multicentre prospective study. Patients completed the Brief Pain Inventory (BPI) to rate the intensity pain (from 0 to 10) at baseline and 4 weeks after radiotherapy. To determine which variables predicted pain response and particularly whether age is a predictor, logistic regression analysis was used. Baseline variables considered were: age (≤65/66–75/>75 years), sex, Eastern Cooperative Oncology Group performance status (0–1/≥2), pretreatment pain score (≤4/5–7/≥8), radiotherapy (single/multiple fraction), primary tumour location, visceral metastases (yes/no), concomitant systemic chemotherapy and bisphosphonate use (yes/no).

Results

Pain response was assessed in the 128 patients who completed BPI pretreatment and at 4 weeks after radiotherapy. According to univariate analysis, pain response was better in over 75‐year‐olds than younger patients: (OR, 3.2; 95% CI, 1.1–9.1; P = 0.031). Response was better in patients receiving multiple fractions rather than a single fraction of 8 Gy (OR, 2.8; 95% CI, 1.2–6.1; P = 0.01), and in patients with a pretreatment pain score ≥8 vs ≤7 (OR, 2.4; 95% CI, 1.1–5.0; P = 0.017). No other variables were significant. Multivariate analysis showed that treatment schedule (OR, 3.4; 95% CI 1.4–7.9; P = 0.004) and pre‐radiotherapy pain score (OR, 2.8; 95% CI 1.3–6.3; P = 0.009) were the only independent predictors of pain response.

Conclusion

All patients with painful bone metastasis should be referred for palliative radiotherapy to relieve the pain regardless of age. Therefore, an older age should not be a reason to withhold palliative radiation treatment.
Noncoding RNAs as therapeutic targets in atherosclerosis with diabetes mellitus
Authors: Tang Ningning , Jiang Shaoyan , Yang Yanyan , Liu Shaoyan , Ponnusamy Murugavel , Xin Hui , Yu Tao
Published: May 2018

Atherosclerosis is one of the major macrovascular complications of diabetes mellitus (DM), and it is the main cause of death from clinical observation. Among various cell types involved in this disorder, endothelial cells, vascular smooth muscle cells (VSMCs), and macrophages play a crucial role in the occurrence and development of this disease. The regulation and stabilization of these cells are a key therapeutic strategy for DM‐associated atherosclerosis. An increasing number of evidences implicate that various types of noncoding RNAs (ncRNAs) play a vital role in many cellular responses as well as in physiological and pathological processes of atherosclerosis and DM that drive atherogenic/antiatherogenic processes in those cells. Encouragingly, many ncRNAs have already been tested in animal experiments or clinical trials showing good performance. In this review, we summarize recent progresses in research on functional regulatory role of ncRNAs in atherosclerosis with DM. More importantly, we illustrate new thoughts and findings relevant to ncRNAs as potential therapeutic targets or biomarkers for atherosclerosis with DM.
Apolipoprotein E region molecular signatures of Alzheimer's disease
Authors: Kulminski Alexander M. , Huang Jian , Wang Jiayi , He Liang , Loika Yury , Culminskaya Irina
Published: May 2018

Although the APOE region is the strongest genetic risk factor for Alzheimer's diseases (ADs), its pathogenic role remains poorly understood. Elucidating genetic predisposition to ADs, a subset of age‐related diseases characteristic for postreproductive period, is hampered by the undefined role of evolution in establishing molecular mechanisms of such diseases. This uncertainty is inevitable source of natural‐selection–free genetic heterogeneity in predisposition to ADs. We performed first large‐scale analysis of linkage disequilibrium (LD) structures characterized by 30 polymorphisms from five genes in the APOE 19q13.3 region (BCAM, NECTIN2, TOMM40, APOE, and APOC1) in 2,673 AD‐affected and 16,246 unaffected individuals from five cohorts. Consistent with the undefined role of evolution in age‐related diseases, we found that these structures, being highly heterogeneous, are significantly different in subjects with and without ADs. The pattern of the difference represents molecular signature of AD comprised of single nucleotide polymorphisms (SNPs) from all five genes in the APOE region. Significant differences in LD in subjects with and without ADs indicate SNPs from different genes likely involved in AD pathogenesis. Significant and highly heterogeneous molecular signatures of ADs provide unprecedented insight into complex polygenetic predisposition to ADs in the APOE region. These findings are more consistent with a complex haplotype than with a single genetic variant origin of ADs in this region.
Concomitant drug abuse of opioid dependent patients in maintenance treatment detected with a multi‐target screening of oral fluid
Authors: Wagner Elias , Raabe Florian , Martin Gabriele , Winter Catja , Plörer Diana , Krause Daniela L. , Adorjan Kristina , Koller Gabriele , Pogarell Oliver
Published: May 2018

Background and Objectives

Numbers of drug‐related deaths have been growing in Europe and the USA, especially those attributable to mixed drug consumption. Overdose deaths account for about one third up to one half of all illicit drug deaths worldwide. In most cases opioids are involved. Opioid maintenance treatment (OMT) is a well‐established therapy option among people with opioid dependence. The aim of this study was to assess concomitant substance abuse in opioid‐dependent patients under OMT in two centers in Munich, Germany.

Methods

Oral fluid samples of opioid‐dependent patients (n = 388) in OMT were randomly collected and analyzed by a multi‐drug screening covering a wide range of psychotropic agents with UPLC‐MS/MS techniques.

Results

Fifty‐one percent of the patients had concomitant substance abuse of at least one non‐prescribed substance, 32% were positive for substances that were not tested in routine urine diagnostics, especially pregabalin. Fifty‐seven percent received take‐home opioid medication, and 26% had contact with underage children. Among the take‐home subgroup, a concomitant substance abuse of 43.5% was detected. Furthermore 52.5% of the patients with contact to underaged children exhibited concomitant substance abuse.

Conclusions

Concomitant substance abuse is a serious issue among OMT patients. Screening for a broader range of substances than usually analyzed, reveals additional relevant abuse among OMT patients, including pregabalin—an anticonvulsant.

Scientific Significance

Our study underscores the importance of monitoring a broad range of substances including others than usually screened in opioid‐dependent patients in OMT. (Am J Addict 2018;27:407–412)
Long‐term efficacy and safety of ustekinumab for Crohn's disease through the second year of therapy
Authors: Sandborn W. J. , Rutgeerts P. , Gasink C. , Jacobstein D. , Zou B. , Johanns J. , Sands B. E. , Hanauer S. B. , Targan S. , Ghosh S. , de Villiers W. J. S. , Colombel J.‐F. , Feagan B. G.
Published: May 2018

Background

In Phase 3 studies of ustekinumab, a fully human monoclonal IL‐12/23p40 antibody approved for moderate‐to‐severe Crohn's disease, patients entered a long‐term extension after completing 8 weeks of induction and 44 weeks of maintenance treatment. Efficacy through 92 weeks and safety through 96 weeks of IM‐UNITI maintenance are reported.

Methods

UNITI‐1 (TNF‐antagonist failures) and UNITI‐2 (conventional therapy failures) patients (N = 1281) entered IM‐UNITI, including 397 ustekinumab intravenous induction responders randomised to subcutaneous ustekinumab 90 mg every 12 weeks, every 8 weeks, or placebo and 884 nonrandomised patients. Dose‐adjustment to 90 mg every 8 weeks occurred in patients randomised to 90 mg every 12 weeks and placebo patients with loss of response (Weeks 8–32). All Week 44 completers could enter the long‐term extension without further dose adjustment. Placebo patients discontinued following study unblinding.

Results

A total of 718 patients (all treated) entered the long‐term extension (298 randomised and 420 not randomised). Overall, 86.5% (621/718) completed Week 96. The proportions of randomised patients in clinical remission were generally maintained from Week 44 through 92 in ustekinumab 90 mg every 12 weeks (77.4% to 72.6%), every 8 weeks (84.1% to 74.4%), and prior dose adjustment groups (63.4% to 53.5%). At Week 92, the proportions of patients in clinical remission were similar in the ustekinumab 90 mg every 12 weeks and every 8 weeks groups and lower in patients with prior dose adjustment. Proportions of patients in clinical remission at Week 92 for all treated every 8 weeks (64.4%) and every 12 weeks (64.3%) groups were lower than randomised every 8 weeks (74.4%) and every 12 weeks (72.6%) groups, but similarly maintained. Safety events (per hundred patient‐years) were similar among all placebo and ustekinumab patients (Week 0‐96), including adverse events (484.39 vs 447.76), serious adverse events (19.24 vs 18.82), and serious infections (4.09 vs 4.02). No dose effect was observed.

Conclusions

Subcutaneous ustekinumab maintained clinical response and remission through Week 92. No new safety signals were observed. ClinicalTrials.gov number NCT01369355.
Effectiveness, treatment completion and safety of sofosbuvir/ledipasvir and paritaprevir/ritonavir/ombitasvir + dasabuvir in patients with chronic kidney disease: an ERCHIVES study
Authors: Butt A. A. , Ren Y. , Puenpatom A. , Arduino J. M. , Kumar R. , Abou‐Samra A‐B.
Published: May 2018

Background

Chronic kidney disease (CKD) was a relative contraindication to hepatitis C virus (HCV) treatment in the interferon/ribavirin era.

Aim

To determine the efficacy, tolerability and safety of sofosbuvir/ledipasvir (SOF/LDV) and paritaprevir/ritonavir/ombitasvir/dasabuvir (PrOD) regimens in persons with CKD.

Methods

We identified persons initiated on a SOF/LDV or PrOD regimen from October 30, 2014 to April 30, 2016. We excluded those with missing HCV genotype or eGFR values. We determined treatment completion and sustained virologic response (SVR) rates, and proportion developing worsening renal function or grade 3/4 haematologic toxicity.

Results

Among 13 663 persons on SOF/LDV±ribavirin, 14% and 1% persons had CKD Stage 3 and 4‐5 respectively, 67.8% completed treatment, 98.2% achieved SVR. Treatment completion or SVR rates did not decline with advanced CKD or ribavirin administration. Among 3961 persons on PrOD±ribavirin, 9% and 3% persons had CKD Stage 3 and 4‐5, respectively, 74.0% completed treatment and 98.2% achieved SVR. A decrease in treatment completion rates was seen in CKD stage 4‐5 and those on ribavirin, but this did not impact SVR rates. A >10 mL/min/1.73 m2 drop in eGFR from baseline was observed in 30%‐38% of persons with baseline eGFR ≥60 mL/min/1.73 m2, but in only 0%‐6% with CKD4‐5. Grade 3/4 anaemia was more frequent in persons with CKD4‐5, but ribavirin co‐administration did not appear to affect this.

Conclusions

SOF/LDV and PrOD achieved high SVR rates in CKD population. Treatment completion rates were lower than expected. A decline in eGFR and development of anaemia were observed in a substantial proportion of persons, but the clinical implications remain unclear.
Anti‐viral therapy is associated with improved survival but is underutilised in patients with hepatitis B virus‐related hepatocellular carcinoma: real‐world east and west experience
Authors: Chen V. L. , Yeh M.‐L. , Le A. K. , Jun M. , Saeed W. K. , Yang J. D. , Huang C.‐F. , Lee H. Y. , Tsai P.‐C. , Lee M.‐H. , Giama N. , Kim N. G. , Nguyen P. P. , Dang H. , Ali H. A. , Zhang N. , Huang J.‐F. , Dai C.‐Y. , Chuang W.‐L. , Roberts L. R. , Jun D. W. , Lim Y.‐S. , Yu M.‐L. , Nguyen M. H.
Published: May 2018

Background

Hepatitis B virus (HBV) is the leading cause of hepatocellular carcinoma (HCC) worldwide. It remains incompletely understood in the real world how anti‐viral therapy affects survival after HCC diagnosis.

Methods

This was an international multicentre cohort study of 2518 HBV‐related HCC cases diagnosed between 2000 and 2015. Cox proportional hazards models were utilised to estimate hazard ratios (HR) with 95% (CI) for anti‐viral therapy and cirrhosis on patients' risk of death.

Results

Approximately, 48% of patients received anti‐viral therapy at any time, but only 17% were on therapy at HCC diagnosis (38% at US centres, 11% at Asian centres). Anti‐viral therapy would have been indicated for >60% of the patients not on anti‐viral therapy based on American criteria. Patients with cirrhosis had lower 5‐year survival (34% vs 46%; P < 0.001) while patients receiving anti‐viral therapy had increased 5‐year survival compared to untreated patients (42% vs 25% with cirrhosis and 58% vs 36% without cirrhosis; P < 0.001 for both). Similar findings were seen for other patient subgroups by cancer stages and cancer treatment types. Anti‐viral therapy was associated with a decrease in risk of death, whether started before or after HCC diagnosis (adjusted HR 0.62 and 0.79, respectively; P < 0.001).

Conclusions

Anti‐viral therapy improved overall survival in patients with HBV‐related HCC across cancer stages and treatment types but was underutilised at both US and Asia centres. Expanded use of anti‐viral therapy in HBV‐related HCC and better linkage‐to‐care for HBV patients are needed.
Physical deconditioning is the common denominator in both obese and overweight subjects with nonalcoholic steatohepatitis
Authors: Argo C. K. , Stine J. G. , Henry Z. H. , Lackner C. , Patrie J. T. , Weltman A. L. , Caldwell S. H.
Published: May 2018

Background

Obesity and decreased physical activity mirror increasing prevalence of nonalcoholic fatty liver disease (NAFLD).

Aim

We aimed to investigate associations between aerobic fitness, anthropometrics and disease parameters in patients with nonalcoholic steatohepatitis (NASH). We hypothesised that NASH subjects have lower aerobic power and capacity than untrained, sedentary, normal subjects.

Methods

Forty subjects (60% obese, 40% overweight) with biopsy‐confirmed NASH and NAFLD activity score (NAS) ≥4 were enrolled in a clinical trial where anthropometrics, laboratories, liver fat content by MRI, activity, and aerobic fitness by cycle ergometry data were obtained.

Results

NASH subjects were significantly deconditioned compared to 148 untrained, sedentary, healthy subjects from our laboratory in aerobic power (VO2peak) (NASH 16.8 ± 6.6 vs control 28.4 ± 10.6 mL/kg/min, P < 0.0001) and capacity (VO2 at lactate threshold [LT]) (NASH 8.3 ± 2.5 vs control 14.1 ± 5.9 mL/kg/min, P < 0.0001). NASH subjects' fitness was comparable to the “least fit” tertile of controls: VO2peak [NASH 16.8 ± 6.6 vs “least fit” 17.3 ± 3.3, P = 0.64]) and VO2 at LT (NASH 8.3 ± 2.5 vs “least fit” 9.3 ± 2.1, P = 0.31). Fitness was similar in obese compared to overweight subjects (adjusted for gender) and was not correlated with visceral adiposity or NAS. Engaging in dedicated cardiovascular activity correlated with higher VO2peak and VO2peak at LT.

Conclusions

Aerobic deconditioning was universally present in NASH subjects. NASH subjects' fitness was similar to our laboratory's “least fit” untrained, sedentary control subjects. Further research investigating NASH patients' ability to improve low baseline aerobic fitness is warranted.
Maize‐dominated crop sequences in northern Germany: Reaction of the weed species communities
Authors: von Redwitz Christoph , Gerowitt Bärbel
Published: May 2018

Questions

Does the mere introduction of maize into the crop sequence change the weed species community? Does a growing share of maize cropping lead to a more problematic weed species community? Do we generally have to expect problematic weed species communities when maize is continuously cultivated?

Location

Northern Germany.

Methods

Weeds in 224 maize fields were surveyed in 3 years and management data of these fields collected for the previous ten cropping years. We arranged seven parameters describing maize cropping patterns and used them as constraining variables in redundancy analysis.

Results

The weed species community was immediately altered by the introduction of maize into the crop sequence. Of those weed species known to be adapted to maize, in our study Echinochloa crus‐galli and to a lesser extent Setaria spp. were strongly related to dense maize cropping patterns, other summer annuals were much less affected.

Conclusions

The spatial growth of areas dedicated to maize cropping will change the weed species communities and, in turn, the arable landscape. E. crus‐galli deserves particular attention due to its tendency to develop herbicide resistance and its positive reaction to dense maize cropping patterns.
Effect of endocannabinoid signalling on cell fate: life, death, differentiation and proliferation of brain cells
Authors: Garcia‐Arencibia Moises , Molina-Holgado Eduardo , Molina‐Holgado Francisco
Published: May 2018

Cell fate events are regulated by different endogenous developmental factors such as the cell micro‐environment, external or remote signals and epigenetic factors. Among the many regulatory factors, endocannabinoid‐associated signalling pathways are known to conduct several of these events in the developing nervous system and in the adult brain. Interestingly, endocannabinoids exert modulatory actions in both physiological and pathological conditions. Endocannabinoid signalling can promote cell survival by acting on non‐transformed brain cells (neurons, astrocytes or oligodendrocytes) and can have either a protumoural or antitumoural effect on transformed cells. Moreover, endocannabinoids are able to attenuate the detrimental effects on neurogenesis and neuroinflammation associated with ageing. Thus, the endocannabinoid system emerges as an important regulator of cell fate, controlling cell survival/cell death decisions depending on the cell type and its environment.

Linked Articles

This article is part of a themed section on 8thEuropean Workshop on Cannabinoid Research. To view the other articles in this section visithttp://onlinelibrary.wiley.com/doi/10.1111/bph.v176.10/issuetoc
The Social Production of Bullying: Expanding the Repertoire of Approaches to Group Dynamics
Authors: Lyng Selma Therese
Published: May 2018

Bullying research has widely included group dynamics as contextual factors. However, explanations addressing the causes of bullying predominantly emphasise individual dysfunctions related to aggression and empathy. Analysing qualitative data from Norwegian schools, this article explores four different group dynamics that may produce bullying behaviours as well as deactivate empathy. Drawing on theories of social hierarchies and ingroups/outgroups, the article offers new approaches to understanding the ways in which the intense markings of social distinctions between positions and cliques in peer culture represent significant social driving forces in school bullying.
Refining area of occupancy to address the modifiable areal unit problem in ecology and conservation
Authors: Moat Justin , Bachman Steven P. , Field Richard , Boyd Doreen S.
Published: May 2018

The modifiable areal unit problem is prevalent across many aspects of spatial analysis within ecology and conservation. The problem is particularly manifested when calculating metrics for extinction risk estimation, for example, area of occupancy (AOO). Although embedded in the International Union for the Conservation of Nature (IUCN) Red List criteria, AOO is often not used or is poorly applied. We evaluated new and existing methods for calculating AOO from occurrence records and devised a method for determining the minimum AOO with a uniform grid. We evaluated the grid cell shape, origin, and rotation with real‐world and simulated data and reviewed the effects on AOO values and possible impacts for species already assessed on the IUCN Red List. The AOO varied by up to 80%, and a ratio of cells to points of 1:1.21 yielded the maximum variation in the number of occupied cells. These findings potentially impact 3% of existing species on the IUCN Red List and species not yet assessed. Our new method combined grid rotation and moving grid origin and gave fast, robust, and reproducible results and, in the majority of cases, achieved the minimum AOO. As well as determining minimum AOO, our method yielded a confidence interval that should be incorporated into existing tools that support species risk assessment. We recommend when recording AOO and other areal measurements that the methods; summary statistics across multiple iterations; angle and origin of the minimum grid; map projection; and datum be recorded, this will lead to more robust species risk assessments.