bluuebunny/crossref_metadata_2025 huggingface dataset:
Can’t change my political disaffection! The role of political disaffection, trust, and resistance to change in internet voting
Authors: Sharma Shwadhin
Published: March 2020

Purpose

This paper aims to put the focus on political disaffection that the voters may have and its impact on their resistance to the changes, thereby influencing intention to adopt Internet voting. This study also examines the impact of perceived risk and technological skills on the trust of the Internet technology and informal networks, such as social influence and media influence on the trust of the government.

Design/methodology/approach

To empirically test the model, an online survey is administered to 851 people who are eligible to vote.

Findings

The findings show that positive media influence and social influence also significantly impact trust in government but trust in government does not necessarily decrease resistance to change and positively impact intention to adopt eVoting. Also, the resistance to change was shown to significantly influence the intention to use Internet voting.

Research limitations/implications

A primary potential limitation of this study is the use of convenience sampling, which may lead to self-selection bias that limits the generalization of our research to all citizens.

Practical implications

Government institutions, as well as political parties, can use the findings of this research to understand how political dissatisfaction such as apathy and cynicism can increase trust in technology and lead to higher participation in online voting.

Originality/value

While the focus on previous literature has been heavily on security and system requirements, this study expands existing research by exploring voting habits, political disaffection, the resistance of change and informal influence on intention to use online voting.
Finite element implementation of viscoelastic and viscoplastic models
Authors: Sepiani Hossein , Polak Maria Anna , Penlidis Alexander
Published: March 2020

Purpose

The purpose of this study is to present a finite element (FE) implementation of phenomenological three-dimensional viscoelastic and viscoplastic constitutive models for long term behaviour prediction of polymers.

Design/methodology/approach

The method is based on the small strain assumption but is extended to large deformation for materials in which the stress-strain relation is nonlinear and the concept of incompressibility is governing. An empirical approach is used for determining material parameters in the constitutive equations, based on measured material properties. The modelling process uses a spring and dash-pot and a power-law approximation function method for viscoelastic and viscoplastic nonlinear behaviour, respectively. The model improvement for long term behaviour prediction is done by modifying the material parameters in such a way that they account for the current test time. The determination of material properties is based on the non-separable type of relations for nonlinear materials in which the material properties change with stress coupled with time.

Findings

The proposed viscoelastic and viscoplastic models are implemented in a user material algorithm of the FE general-purpose program ABAQUS and the validity of the models is assessed by comparisons with experimental observations from tests on high-density polyethylene samples in one-dimensional tensile loading. Comparisons show that the proposed constitutive model can satisfactorily represent the time-dependent mechanical behaviour of polymers even for long term predictions.

Originality/value

The study provides a new approach in long term investigation of material behaviour using FE analysis.
Airbnb – exploring triple bottom line impacts on community
Authors: Caldicott Rodney W. , von der Heidt Tania , Scherrer Pascal , Muschter Sabine , Canosa Antonia
Published: March 2020

Purpose

This paper aims to purposely place community and its stakeholders at the forefront of an investigation of positive and negative social, economic and environmental impacts of the sharing economy in the specific context of Airbnb by drawing upon the triple bottom line (TBL) framework of sustainability.

Design/methodology/approach

A qualitative enquiry through a “scoping approach” with the search of relevant electronic databases identified a range of conceptual and empirical studies in the period from 2008 to 2018 informing a profile focussed on the triple bottom line impacts.

Findings

The criteria limited search yielded 23 focal articles, which investigated or discussed Airbnb impacts on local communities. Analysis of these articles informed a three-pillar tabulation of positive and negative impacts, which are presented against four key stakeholder groupings.

Research limitations/implications

The study is exploratory, and further research, especially confirmatory research, is recommended.

Practical implications

The study’s value extends to praxis. Guided by findings, real-time planning and policy-making are already underway within the authors’ community. Additionally, an extension project, as requested by the community, is now investigating direct traditional accommodation provider impacts.

Social implications

Understanding of the social issues concerning Airbnb and indeed, the wider sharing economy, is broadened through identified need for further social impact research.

Originality/value

To the best of authors’ knowledge, this is one of the first studies to apply a “scoping approach” to holistically illuminate the positive and negative impacts of Airbnb at the micro-level in each of the three domains of sustainability. The research methodology is shown to be effective, with positive community impact, and will easily adapt to other destinations grappling with policy decisions.
Innovation and institutions’ quality: a comparative study between countries
Authors: Kawabata Marcelo Koji , Camargo Junior Alceu Salles
Published: March 2020

Purpose

Innovation has been considered as an essential activity for companies to compete in modern and dynamic business environments. For the nations, innovation is considered a fundamental key activity for sustaining economic growth and competitive advantage over other countries. This paper aims to achieve a better understanding of the relationship between the quality of a country’s institutions and its levels of innovation activities and results.

Design/methodology/approach

Controlling for the effects of the efforts and investments in research and development (R&D) and the foreign direct investments (FDI), this work proceeds to regression analysis to obtain the association between the quality of countries’ institutions and their innovation activities. Data was obtained from the Global Innovation Index (GII) for innovation activities and the Worldwide Governance Index, of the World Bank, for the quality of institutions for 127 countries.

Findings

The results show that the effectiveness of public administration and the regulatory quality are the quality of institution variables associated with the innovation activities. Also, this paper obtained a clustering of countries with a rank regarding not only innovation activities but also the conditions of the institutions’ quality, based on government effectiveness, regulatory quality, R&D, FDI and GII. This new compounded classification divided the 127 countries into three clusters – mature innovators, fresh innovators and structuring for innovation.

Originality/value

New forms of innovations’ ranking viewing can help to understand the conditionings that enhance countries’ and institutions’ competitiveness.
Macrologistic performance and logistics commitments in sales contracts in international supply chains
Authors: Stojanović Đurđica M. , Ivetić Jelena
Published: March 2020

Purpose

This study aims to illuminate the relationship between the logistic performance indexes (LPIs) of trade countries and sharing obligations related to logistics services in delivery among parties in international sales contracts.

Design/methodology/approach

A comprehensive one-year database of Serbian international trade flows is used. The LPIs of 148 countries are related to the Incoterms®rules in international sales contracts that designate the division of obligations between exporters and importers for moving goods. Empirical data were subjected to statistical analysis, where nonparametric correlation and inferential methods were applied. The differences between countries with the highest and lowest LPIs were also examined.

Findings

LPIs positively correlate with logistics commitments in exports and imports. Their impact on the choice of Incoterms®rules differs among the groups of trade terms. Waterway andD-terms are the most sensitive. LPIs of trade countries clearly impact “emission” and “attraction” of the most extended sellers' delivery obligation “packages,” expressed inDrules.

Research limitations/implications

The empirical data are limited to a single country. Further research must explore the relative impact of macrologistic factors on exporters and importers' logistics commitments for building better decision-making support tools.

Practical implications

The results may support suppliers and buyers in sharing their experiences on Incoterms®practice and encourage more rational than intuitive decisions.

Originality/value

This is the first empirical study to quantitatively evidence the sensitivity of groups of Incoterms®rules on the macrologistic environment of trade countries.
Somatic symptoms among prison inmates: contributions of emotion regulation, dispositional mindfulness, and duration of stay in prison
Authors: Ifeagwazi Chuka Mike , Nwokpoku Emeka E. , Chukwuorji JohnBosco Chika , Eze John E. , Abiama Emmanuel Ekpedoho
Published: March 2020

Purpose

The modern prison system is not only a necessity to keep the public safe but also a mode of punishment for crimes. The correctional role of prisons is hampered in situations of mental illness, given that mental illness in the prison or correctional setting is a serious security risk. Few studies have given attention to the modifiable factors that may influence the mental health status of prison inmates, especially in developing countries. The purpose of this paper is to investigate emotion regulation (ER), dispositional mindfulness and duration of stay as factors in somatic symptoms among prison inmates.

Design/methodology/approach

Participants were 209 prison inmates drawn from a prison in Eastern Nigeria, who completed measures of ER (cognitive reappraisal and expressive suppression), mindfulness and somatization.

Findings

Results of a hierarchical multiple regression indicated that cognitive reappraisal predicted somatic complaints but it was only among older prison inmates, while expressive suppression was not a significant predictor of somatic complaints. Dispositional mindfulness was a negative predictor of somatic complaints among younger and older prison inmates. Duration of stay in prison positively predicted somatic complaints among prison inmates in emerging adulthood only (younger inmates), but not among older inmates.

Research limitations/implications

Frequent use of cognitive reappraisal strategy of ER by prisoners may not always be productive in reducing somatic complaints, and the length of time in prison may influence somatic symptoms especially for younger prisoners. The possible benefits of incorporating mindfulness-based therapies in psychosocial interventions to reduce somatic complaints in correctional settings deserves further investigation.

Originality/value

To date, there is limited research on somatic complaints of prisoners in the developing societies, particularly the psychosocial factors that may contribute to mental health problems.
Communicating science in higher education and research institutions
Authors: Schwetje Thorsten , Hauser Christiane , Böschen Stefan , Leßmöllmann Annette
Published: March 2020

Purpose

The paper reports on a research project exploring the change in the organizational context of communicators and communication units in higher education and research institutions (HERIs), the importance of informal processes within their daily work and the great diversity of expectations communicators have to tackle.

Design/methodology/approach

Based on a literature review, a mixed-methods study combining expert interviews with 54 German HERI heads of communication units, an online-survey and a document analysis of organizational characteristics was conducted. Findings were validated in four focus groups.

Findings

The study illuminates the impact of organizational and operational structures of HERIs on communicators and their boundary spanning activities. Due to varying expectations of stakeholders, communicators constantly have to switch roles. Members of HERIs' executive boards affect status and working conditions for communicators in the organization.

Research limitations/implications

Interviews with other HERI actors, especially members of the executive board, are proposed to get more thorough insights into the organizational context of HERIs and the mutual expectations of different internal stakeholders.

Practical implications

Insights from the project may help HERI actors to reflect their organizational context and to identify potentially contentious structures or processes.

Originality/value

Communicating science sometimes clashes with complex organizational and operational structures. Despite the “organizational turn” in HERI research, there is a lack of data on the relation between communicators, their communication units and the larger organizational context. The exploratory study addresses this gap.
Dynamics of capital controls: panel evidence from Asia
Authors: Guru Biplab Kumar , Yadav Inder Sekhar
Published: March 2020

Purpose

This study empirically examines the effect of capital controls on the volume and composition of capital flows at aggregated as well as at disaggregated level by different asset classes such as debt, FDI, equity, and derivatives.

Design/methodology/approach

Several dynamic panel SYS-GMM models are employed on two sets of unique data on cross-border capital flows and capital control index along with control variables at aggregated and disaggregated level by different asset classes during 1995–2015 for a sample of 31 Asian economies.

Findings

Econometric findings suggest that higher capital controls effectively reduce gross capital flows. The reduction in gross capital flows is largely found to be on account of effectiveness of controls on equity flows. However, the impact of controls on overall debt and derivative flows is found to be insignificant. Further, it was found that an increase in direct capital controls disaggregated by inflow and outflow categories significantly reduced the inflow of debt and equity + FDI flows and outflow of equity + FDI and derivative flows. Finally, the study did not find any substitution effect (due to indirect controls) and net effect on capital flows.

Practical implications

Results of such empirical examination may enable governments in respective countries to pursue prudent and rational capital controls as a shield against capital flight and shock transmission.

Social implications

Preventing capital flight through effective controls has macroeconomic benefits such as maintaining stability in income, growth, interest rate, exchange rate, and employment levels for the society.

Originality/value

The primary contribution of the study is the analysis of effectiveness of capital controls disaggregated by different asset categories such as debt, equity, FDI, and derivatives using two unique recent data sets for a large sample of Asian economies.
Issues and challenges of user and data interaction in healthcare-related IoT
Authors: Zou Ning , Liang Shaobo , He Daqing
Published: March 2020

Purpose

The Internet of Things (IoT), which enables smart objects to collect and exchange data, has a variety of application domains used in everyday life including healthcare. As a set of promising next-generation technologies in the healthcare domain, Healthcare-related Internet of Things (H-IoT) promises to facilitate better healthcare by offering data-driven insights. While effective in practice at large, emerging data concerns arise because of the inscrutable black-box systems. Inspired by the notion of human data interaction, this paper seeks to understand how people engage with the H-IoT data that is about and produced by themselves and to elucidate the main data issues and challenges involved in the development of H-IoT.

Design/methodology/approach

This work conducted a comprehensive survey and integrated the method of content analysis by systematically review the recently published H-IoT research work in the healthcare domain.

Findings

This study thoroughly surveyed more than 300 research studies published in the last decades and classified seven H-IoT end-user groups, and three H-IoT data types that are important to H-IoT comprehension. Attention to human data interaction, our study also highlights several critical issues associated with this notion in the context of H-IoT.

Originality/value

This study will support H-IoT research by characterizing the data issues and challenges exist in the context of H-IoT user and data interaction. The findings will provide insights in designing for effective interactions with data in the H-IoT.
What drives Instagram usage? User motives and personality traits
Authors: Kocak Esra , Nasir V. Aslihan , Turker Hande B.
Published: March 2020

Purpose

Social networking sites (SNS) have become extensively used communication environments as a result of the advancements in online technologies, and among various SNS platforms, Instagram is currently the most prominent image-based network. Since usage motives for alternative SNS environments with different outstanding benefits are expected to vary, this study has focused mainly on extracting the key context-specific usage motives of Instagram. Another purpose of this study is to figure out personality traits differences among Instagram user segments.

Design/methodology/approach

An online survey was designed, and a total of 690 fully completed questionnaires was collected, and 507 of the respondents were Instagram users. After conducting factor analysis, six main usage motive categories have been revealed and named as self-expression, recording, socialization, recreation, creativity, and prying.

Findings

Instagram users have been clustered as passionate, distant, and spectator users based on their usage motives. Ultimately, personality differences among these clusters have been explored using the Big Five Inventory (BFI) and two additional traits, social interaction anxiety, and fear of negative evaluation. Openness to experience, social interaction anxiety, and fear of negative evaluation were found to be significantly different among these clusters.

Originality/value

Discovering the motives of SNS usage, segmenting users based on these motives, and then portraying the personality traits of each segment gives important clues about how SNSs can better design their interfaces and generate content for attracting users in different segments.
Balancing deterrence: Iran-Israel relations in a turbulent Middle East
Authors: Maher Nora
Published: March 2020

Purpose

This paper aims to examine the regional dynamics that further consolidated Israel’s national security in the Middle East in the aftermath of the Arab Spring, reflecting upon the nuclear challenge between Iran and Israel and Iran's expanding activities in the region.

Design/methodology/approach

To prove the central argument, the study uses a conceptual framework that centers on deterrence as the main approach used by states to consolidate their influence in the Middle East region.

Findings

Iran's nuclear progress and influence in the region has strengthened Israel’s security and fostered an unprecedented open rapprochement led by USA efforts with the Gulf regimes.

Originality/value

The paper draws particular attention to the Iran–Israel nuclear competency, and the Israeli preferred policy options regarding Iranian activities in the region amid turbulent Middle East. In addition, the paper offers insight to the regional dynamics that further consolidated Israel’s national security in the region while maintaining a status of Arab vulnerability and backwardness.
How software developers instigated the transformation of management
Authors: Denning Stephen
Published: March 2020

Purpose

When firms embrace an adaptive interactive development mindset—obsessing over the needs of customers, systematically working in small self-organizing teams working in short cycles, operating as a network rather than command-and-control hierarchy—its software developers can work with management to innovate new customer value.

Design/methodology/approach

The article identifies the reasons that the need for innovative, rapid software developments has had on the way corporations are organized and managed.

Findings

Software development went from being a drag on organizational performance to being a key driver of success.

Practical implications

Business agility thus isn’t just a matter of applying agile software practices to other functions.

Originality/value

Computer software, including artificial intelligence, machine learning and cloud computing, is now enabling, improving or accelerating almost everything that humans, machines and organizations do. This article explains why an Agile mindset is the key to winning in the competitive race to offer high-value, innovative, digitally powered products and services.
Initial development of a measure of evidence‐informed professional thinking
Authors: Benfield Angela M. , Johnston Mark V.
Published: March 2020

Background and aims

A number of theories have been proposed on clinical expertise and its development in occupational therapy and allied health professions. Clinical reasoning, outcome measurement and evidence‐based practice are names for leading conceptualisations. The aim of this research was to develop an operational measure of habits of mind and practice that constitute these desirable professional activities amongst professional therapists.

Methods

Items were developed on the basis of literature review and feedback from an expert panel. An online self‐report survey was completed by 107 occupational therapists and other allied health clinicians. Rasch analysis was used to identify and calibrate items that fit the criteria for equal‐interval measurement. Residuals from identified equal‐interval dimensions were examined using principal components analysis to identify multidimensionality.

Results

A two‐dimension solution employing 32 items was identified. The first dimension comprised items on Critical Clinical Reasoning and had an item separation of 8.49 (0.99 reliability) and a person separation of 2.93 (0.90 reliability). The second dimension comprised items on Evidence‐Informed Practice behaviours and had an item separation of 6.19 (0.97 reliability) and a person separation of 2.97 (0.90 reliability). These dimensions were positively correlated (r = .778,p < .001). We named the overall scale ‘Evidence‐Informed Professional Thinking’, or EIPT. The EIPT measures correlated significantly with 12 of 13 relevant external criterion items.

Conclusion

Evidence‐informed professional thinking can be measured in terms of two correlated probabilistically equal‐interval dimensions: Critical Clinical Reasoning and Evidence‐Informed Practice behaviours. The EIPT measure should be useful in research on development and application of clinical expertise, quality and outcomes of care and implementation of improved practices among practicing therapists in clinical treatment settings. Further research is recommended to understand the generalisability, strengths, limitations and correlates of EIPT.
Analyses of microRNAs and transcriptomes in the midgut of Spodoptera litura feeding on Brassica juncea
Authors: Zou Xiao‐Peng , Lin Yi‐Guang , Cen Yong‐Jie , Ma Kang , Qiu Bin‐Bin , Feng Qi‐Li , Zheng Si‐Chun
Published: March 2020

Spodoptera litura is a destructive agricultural pest in tropical and subtropical areas. Understanding the molecular mechanisms of S. litura adaptation to its preferred host plants may help identify target genes useful for pest control. We used high‐throughput sequencing to characterize the expression patterns of messenger RNAs (mRNAs) and microRNAs (miRNAs) in the midgut of S. litura fed on Brassica juncea for 6 h and 48 h. A total of 108 known and 134 novel miRNAs were identified, 29 miRNAs and 237 mRNAs were differentially expressed at 6 h of B. juncea feeding, 26 miRNAs and 433 mRNAs were differentially expressed at 48 h. For the mRNAs, the up‐regulated genes were mostly enriched in detoxification enzymes (cytochrome P450, esterase, glutathione S‐transferase, uridine diphosphate‐glucuronosyl transferase), while the down‐regulated genes were mostly enriched in proteinases and immune‐related genes. Furthermore, most detoxification enzymes begin to up‐regulate at 6 h, while most digestion and immune‐related genes begin to up‐ or down‐regulate at 48 h. Eighteen and 37 differently expressed transcription factors were identified at 6 h and 48 h, which may regulate the functional genes. We acquired 136 and 41 miRNA versus mRNA pairs at 6 h and 48 h, respectively. Some down‐regulated and up‐regulated miRNAs were predicted to target detoxification enzymes and proteinases, respectively. Real‐time quantitative polymerase chain reaction of nine randomly selected miRNAs and 28 genes confirmed the results of RNA‐seq. This analyses of miRNA and mRNA transcriptomes provides useful information about the molecular mechanisms of S. litura response to B. juncea.
Arterial contrast extravasation in severe seat belt‐related female breast trauma on CT: Conservative management at a level 1 trauma centre
Authors: Teh Derek T , Weber Dieter G , Wylie Elizabeth J
Published: March 2020

Seat belt‐related female breast trauma (SFBT) is an uncommon cause of haemorrhage following motor vehicle collision. Classification systems have been used to grade the severity of SFBT, ranging from mild class I to severe class IV injuries with evidence of active haemorrhage. In the case of class IV injuries, contrast extravasation represents active haemorrhage, prompting angiographic embolisation or surgery to arrest the bleed. Contrary to the majority of reports published in the literature, our institution has been successful with conservative management of class IV SFBT. None of the patients required specific intervention to control haemorrhage from SFBT.
Case Series: Rapid Induction Onto Long Acting Buprenorphine Injection for High Potency Synthetic Opioid Users
Authors: Mariani John J. , Mahony Amy , Iqbal Muhammad N. , Luo Sean X. , Naqvi Nasir H. , Levin Frances R.
Published: March 2020

Background and Objectives

Highly potent synthetic opioids (HPSO) are increasingly responsible for opioid overdose deaths in the United States.

Methods

In an open‐label, uncontrolled trial to test the feasibility of extended‐release buprenorphine (BXR) injection treatment of heroin‐using individuals with opioid use disorder testing positive for HPSO, participants were enrolled and began an induction with sublingual BXR (n = 5). During the induction, ancillary medications (clonidine, clonazepam, zolpidem, and prochlorperazine) were provided for breakthrough opioid withdrawal symptoms.

Results

Two participants received the BXR injection on the second day of the induction and three participants on the third day.

Discussion and Conclusion

All five participants were retained at least 1‐month postinduction.

Scientific Significance

It may be feasible to provide BXR treatment to HPSO‐positive heroin users rapidly to achieve clinical stabilization. (Am J Addict 2020;00:00–00)
Semen endocannabinoids are correlated to sperm quality in a cohort of 200 young Swiss men
Authors: Zufferey Fanny , Donzé Nicolas , Rahban Rita , Senn Alfred , Stettler Eric , Rudaz Serge , Nef Serge , Rossier Michel F.
Published: March 2020

Background

A role for endocannabinoids in the male and female reproductive systems has been highlighted during the recent decades. Some of these compounds bind the cannabinoid CB1 receptor, which is abundantly expressed in the central nervous system but also present in the reproductive system, while others act as ‘entourage compounds’ modulators.

Objectives

The present study aimed at evaluating the relationship between sperm quality and endocannabinoid profiles in a cohort of 200 young Swiss men and whether the presence of specific xenobiotics could influence these profiles.

Materials and methods

Semen analysis was performed according to WHO guidelines. Endocannabinoid profiles in blood and semen, as well as bisphenol A and S in urine, were determined by LC‐MSMS methods. The presence of selected drugs was tested in urine by immunological screening, and urinary tetrahydrocannabinol (THC) metabolites were quantified by GC‐MS.

Results

Anandamide concentrations in seminal fluid and oleoylethanolamide (OEA) concentrations in blood serum appeared inversely correlated with sperm motility, while semen palmytoylethanolamide (PEA) was positively linked to sperm concentration. Moreover, OEA and PEA in seminal fluid were associated with better sperm morphology. Interestingly, the concentrations of the same endocannabinoids measured in both blood and semen were not correlated, and the presence of THC metabolites in some individuals was linked to lower concentrations of endocannabinoids.

Conclusions

In the context of the general decline of the sperm count observed within the male population, endocannabinoids in semen constitute a class of promising biochemical markers that open new perspectives as a complement for the usual evaluation of semen quality or for the toxicological screening of individuals' exposure to putative endocrine disruptors.
Forging ahead or moving back: dilemmas and disappointments of novel agents for myeloproliferative neoplasms
Authors: McLornan Donal P. , Harrison Claire N.
Published: March 2020

The common ‘Philadelphia chromosome’‐negative myeloproliferative neoplasms (MPN) comprise essential thrombocythaemia, polycythaemia vera and myelofibrosis. These are clinically diverse disorders and present many challenges during their course, ranging from the management of very indolent, chronic‐phase disease through to very aggressive stages frequently associated with poor quality of life, heavy symptom burdens and potentially life expectancies of <18 months. Their management also requires expertise in thrombosis and haemostasis in addition to marrow failure, debilitating symptom control and balancing the ‘pros and cons’ of intensive therapy such as allogeneic stem cell transplant versus novel and established therapies. In the past 15 years this field has seen rapid advances following an understanding of the pivotal importance of constitutive Janus kinase/signal transducers and activators of transcription (JAK/STAT) signalling, the interplay of the wider genomic landscape and the development of updated diagnostic criteria, prognostic scores and targeted therapies. In this article, we review the successes and failures of novel agents and approaches to MPN management.
Differential hepatoprotective role of the cannabinoid CB1 and CB2 receptors in paracetamol‐induced liver injury
Authors: Rivera Patricia , Vargas Antonio , Pastor Antoni , Boronat Anna , López‐Gambero Antonio Jesús , Sánchez‐Marín Laura , Medina‐Vera Dina , Serrano Antonia , Pavón Francisco Javier , de la Torre Rafael , Agirregoitia Ekaitz , Lucena María Isabel , Rodríguez de Fonseca Fernando , Decara Juan , Suárez Juan
Published: March 2020

Background and Purpose

Protective mechanisms of the endogenous cannabinoid system against drug‐induced liver injury (DILI) are actively being investigated regarding the differential regulatory role of the cannabinoid CB1 and CB2 receptors in liver fibrogenesis and inflammation.

Experimental Approach

The 2‐arachidonoylglycerol (2‐AG)‐related signalling receptors and enzymatic machinery, and inflammatory/fibrogenic factors were investigated in the liver of a mouse model of hepatotoxicity induced by acute and repeated overdoses (750 mg·kg−1·day−1) of paracetamol (acetaminophen), previously treated with selective CB1 (ACEA) and CB2 (JWH015) agonists (10 mg·kg−1), or lacking CB1 and CB2 receptors.

Key Results

Acute paracetamol increased the expression of CB2, ABHD6 and COX‐2, while repeated paracetamol increased that of CB1 and COX‐2 and decreased that of DAGLβ. Both acute paracetamol and repeated paracetamol decreased the liver content of acylglycerols (2‐AG, 2‐LG and 2‐OG). Human liver samples from a patient suffering APAP hepatotoxicity confirmed CB1 and CB2 increments. Acute paracetamol‐exposed CB2 KO mice had higher expression of the fibrogenic αSMA and the cytokine IL‐6 and lower apoptotic cleaved caspase 3. CB1 deficiency enhanced the repeated APAP‐induced increases in αSMA and cleaved caspase 3 and blocked those of CYP2E1, TNF‐α, the chemokine CCL2 and the circulating γ‐glutamyltransferase (γGT). Although JWH015 reduced the expression of αSMA and TNF‐α in acute paracetamol, ACEA increased the expression of cleaved caspase 3 and CCL2 in repeated paracetamol.

Conclusion and Implications

The differential role of CB1 versus CB2 receptors on inflammatory/fibrogenic factors related to paracetamol‐induced hepatotoxicity should be considered for designing alternative therapies against DILI.
Low‐concentration DMSO accelerates skin wound healing by Akt/mTOR‐mediated cell proliferation and migration in diabetic mice
Authors: Guo Wei , Qiu Wei , Ao Xiang , Li Weiqiang , He Xiao , Ao Luoquan , Hu Xueting , Li Zhan , Zhu Ming , Luo Donglin , Xing Wei , Xu Xiang
Published: March 2020

Background and Purpose

DMSO has been found to promote tissue repair. However, the role of DMSO in diabetic skin wound healing and the underlying molecular mechanisms are still unclear.

Experimental Approach

The effects of DMSO on wound healing were evaluated by HE staining, immunohistochemistry and collagen staining using a wound model of full‐thickness skin resection on the backs of non‐diabetic or diabetic mice. Real‐time cell analysis and 5‐ethynyl‐2′‐deoxyuridine incorporation assays were used to study the effect of DMSO on primary fibroblast proliferation. A transwell assay was used to investigate keratinocyte migration. The associated signalling pathway was identified by western blotting and inhibitor blocking. The effect of DMSO on the translation rate of downstream target genes was studied by RT‐qPCR of polyribosome mRNA.

Key Results

We found that low‐concentration DMSO significantly accelerated skin wound closure by promoting fibroblast proliferation in both nondiabetic and diabetic mice. In addition, increased migration of keratinocytes may also contribute to accelerated wound healing, which was stimulated by increased TGF‐β1 secretion from fibroblasts. Furthermore, we demonstrated that this effect of DMSO depends on Akt/mTOR‐mediated translational control and the promotion of the translation of a set of cell proliferation‐related genes. As expected, DMSO‐induced wound healing and cell proliferation were impaired by rapamycin, an inhibitor of Akt/mTOR signalling.

Conclusion and Implications

DMSO can promote skin wound healing in diabetic mice by activating the Akt/mTOR pathway. Low‐concentration DMSO presents an alternative medication for chronic cutaneous wounds, especially for diabetic patients.
In silico and in vitro studies of a number PILs as new antibacterials against MDR clinical isolate Acinetobacter baumannii
Authors: Trush Maria M. , Kovalishyn Vasyl , Hodyna Diana , Golovchenko Olexandr V. , Chumachenko Svitlana , Tetko Igor V. , Brovarets Volodymyr S. , Metelytsia Larysa
Published: March 2020

QSAR analysis of a set of previously synthesized phosphonium ionic liquids (PILs) tested against Gram‐negative multidrug‐resistant clinical isolate Acinetobacter baumannii was done using the Online Chemical Modeling Environment (OCHEM). To overcome the problem of overfitting due to descriptor selection, fivefold cross‐validation with variable selection in each step of the model development was applied. The predictive ability of the classification models was tested by cross‐validation, giving balanced accuracies (BA) of 76%–82%. The validation of the models using an external test set proved that the models can be used to predict the activity of newly designed compounds with a reasonable accuracy within the applicability domain (BA = 83%–89%). The models were applied to screen a virtual chemical library with expected activity of compounds against MDR Acinetobacter baumannii. The eighteen most promising compounds were identified, synthesized, and tested. Biological testing of compounds was performed using the disk diffusion method in Mueller‐Hinton agar. All tested molecules demonstrated high anti‐A. baumannii activity and different toxicity levels. The developed classification SAR models are freely available online at http://ochem.eu/article/113921 and could be used by scientists for design of new more effective antibiotics.
Coexistence of autosomal dominant polycystic kidney disease type 1 and hereditary renal hypouricemia type 2: A model of early‐onset and fast cyst progression
Authors: Peces Ramón , Mena Rocio , Peces Carlos , Cuesta Emilio , Selgas Rafael , Barruz Pilar , Lapunzina Pablo , Nevado Julián
Published: March 2020

Autosomal dominant polycystic kidney disease (ADPKD) is a heterogeneous inherited disease characterized by renal and extrarenal manifestations with progressive fluid‐filled cyst development leading to end‐stage renal disease. The rate of disease progression in ADPKD exhibits high inter‐ and intrafamilial variability suggesting involvement of modifier genes and/or environmental factors. Renal hypouricemia (RHUC) is an inherited disorder characterized by impaired tubular uric acid transport with severe complications, such as acute kidney injury and chronic kidney disease (CKD). However, the two disorders have distinct and well‐delineated genetic, biochemical, and clinical findings. Only a few cases of coexistence of ADPKD and RHUC (type 1) in a single individual have been reported. We report a family with two members: an ADPKD 24‐year‐old female which presented bilateral renal cysts in utero and hypouricemia since age 5, and her mother with isolated hypouricemia. Next‐generation sequencing identified two mutations in two genes PKD1 and SLC2A9 in this patient and one isolated SLC2A9 mutation in her mother, showing RHUC type 2, associated to CKD. The coexistence of these two disorders provides evidence of SLC2A9 variant could act as a modifier change, with synergistic actions, that could promote cystogenesis and rapid ADPKD progression. This is the first case of coexistence of PKD1 and SLC2A9 mutations treated with tolvaptan.
Mortality trends around the one‐year survival mark after heart, liver, and lung transplantation in the United States
Authors: Nathan Ashwin S. , Blebea Catherine , Chatterjee Paula , Thomasson Arwin , Diamond Joshua M. , Groeneveld Peter W. , Giri Jay , Goldberg Hilary J. , Courtwright Andrew M.
Published: March 2020

Introduction

One‐year post‐transplant survival is a significant quality measure for solid organ transplant programs in the United States. It is not known whether the use of this metric is associated with changes in life‐sustaining clinical practices that would delay mortality for solid organ recipients until just beyond the one‐year time point.

Methods

We compared trends in mortality in the time period immediately preceding the one‐year post‐transplant mark compared to the period immediately after using second‐order Cox proportional hazard regression models.

Results

Among recipients of heart, liver, and lung transplantation, mortality did not decrease significantly in the period immediately before day 365 or increase in the 14 days thereafter. There was an increased adjusted hazard of mortality in the 30 days following day 365 among lung transplant recipients (HR 1.33, 95% CI 1.03‐1.72, P = .03) with a 0.76% absolute mortality rate (94 deaths) in month 12 following lung transplantation and a 1.14% absolute mortality rate in month 13 (113 deaths).

Conclusion

Although we did not find evidence that life‐sustaining treatment is routinely continued until just beyond the one‐year mark in heart and liver transplantation recipients, there was an unexpected increased risk of mortality in the 30 days following day 365 among lung transplant recipients.
Temporal trends and outcomes of patients waiting on left ventricular assist devices and inotropes for heart transplantation
Authors: Briasoulis Alexandros , Adegbala Oluwole , Akintoye Emmanuel , Alvarez Paulino
Published: March 2020

We sought to evaluate the trends and outcomes of patients with left ventricular assist devices (LVADs) and inotropes at the time of listing for heart transplantation. Adults with an LVAD implanted and listed with 1A status were identified in the United Network for Organ Sharing (UNOS) registry between 2010 and 2017. Patients were grouped according to the presence or absence of inotropes at the time of listing and transplantation. A total of 2714 patients were included in the study including 664 patients on inotropes at the time of listing, 235 at the time of transplantation, and 118 on inotropes both at listing and at the time of transplantation. Patients on LVAD and inotropes at the time of listing were more frequently supported with a right ventricular assist device (RVAD) (P < .001), had higher risk of death in the waiting list (sub‐hazard ratio [SHR] = 1.48, 95% CI 1.14‐1.90, P = .002), and were less likely to be transplanted (SHR = 0.70, 95% CI 0.63‐0.78, P < .001) compared with those not on inotropes, after adjusting for described confounders. Approximately 1 in 10 LVAD recipients listed as status 1A are on inotropic therapy at the time of heart transplantation. Patients on LVAD and inotropes have worse outcomes in terms of survival and lower rates of transplantation.
Primary Care Prescription Drug Use and Related Actionable Drug‐Gene Interactions in the Danish Population
Authors: Lunenburg Carin Adriana Theodora Catharina , Hauser Alexander Sebastian , Ishtiak‐Ahmed Kazi , Gasse Christiane
Published: March 2020

Pharmacogenetics (PGx) aims to improve drug therapy using the individual patients’ genetic make‐up. Little is known about the potential impact of PGx on the population level, possibly hindering implementation of PGx in clinical care. Therefore, we investigated how many patients use actionable PGx drugs, have actionable genotypes or phenotypes and which patients could benefit the most of PGx testing. We included PGx recommendations from two international PGx consortia (Clinical Pharmacogenetics Implementation Consortium (CPIC) and Dutch Pharmacogenetics Working Group (DPWG)). Using data from publically accessible sales information drawn from the Danish Register of Medicinal Product Statistics (MEDSTAT), we identified the number of users of actionable prescription PGx drugs among the total Danish population in 2017. We estimated actionable genotypes or phenotypes based on reported frequencies from literature. We identified 49 drug‐gene interactions related to 41 unique prescription drugs. The estimated median frequency of actionable genotypes or phenotypes among prescription drug users was 25% (interquartile range 7–26%). Six of 41 drugs were used more than twice as much in women. Actionable PGx drugs were most frequently used by 45–79 year old patients (62%), followed by 25–44 year old patients (18%). Almost half of the actionable PGx drugs (19/41) were psychotropics (i.e., antidepressants, antipsychotics, or psychostimulants). PGx testing can have a substantial impact on the population, as one in four prescription drug users has an actionable genotype or phenotype and could thus benefit from PGx testing. We advocate for prospective panel‐based PGx testing at the time of the first PGx drug prescription (“as needed”), with PGx results ready prior to start of the first, and all future, therapies.
Combined continuous glucose monitoring and subcutaneous insulin infusion versus self‐monitoring of blood glucose with optimized multiple injections in people with type 1 diabetes: A randomized crossover trial
Authors: Dicembrini Ilaria , Pala Laura , Caliri Mariasmeralda , Minardi Silvia , Cosentino Claudia , Monami Matteo , Mannucci Edoardo
Published: March 2020

Aim

To investigate the efficacy of a combination of continuous glucose monitoring (CGM) and continuous subcutaneous insulin infusion (CSII) versus an optimized degludec‐based multiple daily injections (MDI) regimen + self‐monitoring of blood glucose (SMBG) in people with type 1 diabetes with regard to optimizing glucose control.

Material and methods

The trial included 28 individuals who underwent a 4‐week run‐in phase, and were then randomized 1:1 to: (a) CSII + CGM followed by MDI + SMBG or (b) an MDI basal‐bolus regimen followed by CSII + CGM.

Results

In patients randomized to the CSII + CGM → MDI + SMBG arm, a significant reduction in glycated haemoglobin (HbA1c) versus baseline was found at the end of the first phase (CSII + CGM) without significant variation in the following MDI + SMBG phase. In the arm randomized to the MDI + SMBG → CSII + CGM sequence, a significant improvement in HbA1c was observed in the first phase (MDI + SMBG), together with a further decrease in the following CSII + CGM phase. In the comparison of the two treatments using a mixed linear model, CSII + CGM was superior to MDI + SMBG with respect to change in HbA1c (P = 0.001).

Conclusions

This study suggests that CSII + CGM improves glycaemic control without relevant safety issues in type 1 diabetes, in comparison with MDI + SMBG.
Response of the cerebral vasculature to systemic carbon monoxide administration—Regional differences and sexual dimorphism
Authors: Oliveira Sara R. , Castelhano João , Sereno José , Vieira Helena L. A. , Duarte Carlos B. , Castelo‐Branco Miguel
Published: March 2020

Previous studies about the modulation of the vasculature by CO were performed exclusively in male or sexually immature animals. Understanding the sex differences regarding systemic drug processing and pharmacodynamics is an important feature for safety assessment of drug dosing and efficacy. In this work, we used CORM‐A1 as source of CO to examine the effects of this gasotransmitter on brain perfusion and the sex‐dependent differences. Dynamic contrast‐enhanced imaging (DCE)‐based analysis was used to characterize the properties of CO in the modulation of cerebral vasculature in vivo, in adult C57BL/6 healthy mice. Perfusion of the temporal muscle, maxillary vein and in hippocampus, cortex and striatum was analysed for 108 min following CORM‐A1 administration of 3 or 5 mg/kg. Under control conditions, brain perfusion was lower in females when compared with males. Under CO treatment, females showed a surprisingly overall reduced perfusion compared with controls (F = 3.452, p = .0004), while no major alterations (or even the expected increase) were observed in males. Cortical structures were only modulated in females. A striking female‐dominated vasoconstriction effect was observed in the hippocampus and striatum following administration of CO, in this mixed‐sex cohort. As these two regions are implicated in episodic and procedural memory formation, CO may have a relevant impact in learning and memory.