bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparing the impact of three different experiential approaches to entrepreneurship in education
Authors: Lackéus Martin
Published: June 2020

Purpose

Three different pedagogical approaches grounded in three different definitional foundations of entrepreneurship have been compared in relation to their effects on students. They are: (1) “Idea and Artefact-Creation Pedagogy” (IACP), grounded in opportunity identification and creation, (2) “Value-Creation Pedagogy” (VaCP), grounded in value creation and (3) “Venture-Creation Pedagogy” (VeCP), grounded in organisation creation.

Design/methodology/approach

Data were collected at 35 different sites where education was deemed to be entrepreneurial and experiential. A quantitative, smartphone app-based data collection method was used alongside a qualitative interview approach. 10,953 short-survey responses were received from 1,048 participants. Responses were used to inform respondent selection and discussion topics, in 291 student and teacher interviews. Comparative analysis was then conducted.

Findings

The three approaches resulted in very different outcomes, both in magnitude and in kind. VaCP had strong effects on entrepreneurial competencies, on student motivation and on knowledge and skills acquisition. VeCP had weaker effects on knowledge and skills acquisition. IACP had weak effects on all outcomes probed for. Differences were attributed to variation in prevalence of certain emotional learning events and to variation in purpose as perceived by students.

Research limitations/implications

VaCP could serve as an escape from the potential dilemma faced by many teachers in entrepreneurial education, of being caught between two limiting courses of action; a marginal VeCP approach and a fuzzy IACP one. This could prompt policymakers to reconsider established policies. However, further research in other contexts is needed, to corroborate the extent of differences between these three approaches.

Originality/value

Most impact studies in experiential entrepreneurial education focus only on organisation-creation-based education. This study contributes by investigating entrepreneurial education that is also grounded in two other definitional foundations. Allowance has been made for novel comparative conclusions.
Scoping the application of primary care advanced clinical practice roles in England
Authors: Thompson Juliana , Tiplady Sue , Hodgson Phil , Proud Carole
Published: June 2020

Purpose

This study aims to scope the profile and application of an advanced clinical practitioner (ACP) roles in primary care in the North of England and how these roles meet the requirements of Health Education England's (HEE’s) ACP workforce capability framework.

Design/methodology/approach

A two-stage design was used. Stage 1 analysed health and social care workforce intelligence reports to inform scoping of numbers of ACPs working in primary care. Stage 2 used two surveys. Survey 1 targeted ACP leads and collected strategic-level data about ACP application. Survey 2 targeted staff who perceived themselves to be working as ACPs. Survey 2 was in three parts. Part 1 collected demographic data. Part 2 required participants to record their perceived competence against each of the HEE ACP framework capability criteria. Part 3 required respondents to identify facilitators and barriers to ACP practice.

Findings

Despite the introduction of HEE's ACP capability framework, there is inconsistency and confusion about the ACP role. The results indicated a need for standardisation of role definition and educational and practice requirements. The results also suggested that some ACPs are not working to their full potential, while some staff who are employed as “gap-fillers” to provide routine clinical services perceive themselves as ACPs despite not working at the ACP level.

Originality/value

Although previous research has explored the application of ACP practice in primary care, few studies have considered ACP application in the light of the introduction of workforce capability frameworks aimed at standardising ACP practice.
The case for blockchain in IoT identity management
Authors: Sousa Patrícia R. , Resende João S. , Martins Rolando , Antunes Luís
Published: June 2020

Purpose

The aim of this paper is to evaluate the use of blockchain for identity management (IdM) in the context of the Internet of things (IoT) while focusing on privacy-preserving approaches and its applications to healthcare scenarios.

Design/methodology/approach

The paper describes the most relevant IdM systems focusing on privacy preserving with or without blockchain and evaluates them against ten selected features grouped into three categories: privacy, usability and IoT. Then, it is important to analyze whether blockchain should be used in all scenarios, according to the importance of each feature for different use cases.

Findings

Based on analysis of existing systems, Sovrin is the IdM system that covers more features and is based on blockchain. For each of the evaluated use cases, Sovrin and UniquID were the chosen systems.

Research limitations/implications

This paper opens new lines of research for IdM systems in IoT, including challenges related to device identity definition, privacy preserving and new security mechanisms.

Originality/value

This paper contributes to the ongoing research in IdM systems for IoT. The adequacy of blockchain is not only analyzed considering the technology; instead the authors analyze its application to real environments considering the required features for each use case.
The big data-business strategy interconnection: a grand challenge for knowledge management. A review and future perspectives
Authors: Ciampi Francesco , Marzi Giacomo , Demi Stefano , Faraoni Monica
Published: June 2020

Purpose

Designing knowledge management (KM) systems capable of transforming big data into information characterised by strategic value is a major challenge faced nowadays by firms in almost all industries. However, in the managerial field, big data is now mainly used to support operational activities while its strategic potential is still largely unexploited. Based on these considerations, this study proposes an overview of the literature regarding the relationship between big data and business strategy.

Design/methodology/approach

A bibliographic coupling method is applied over a dataset of 128 peer-reviewed articles, published from 2013 (first year when articles regarding the big data-business strategy relationship were published) to 2019. Thereafter, a systematic literature review is presented on 116 papers, which were found to be interconnected based on the VOSviewer algorithm.

Findings

This study discovers the existence of four thematic clusters. Three of the clusters relate to the following topics: big data and supply chain strategy; big data, personalisation and co-creation strategies and big data, strategic planning and strategic value creation. The fourth cluster concerns the relationship between big data and KM and represents a ‘bridge’ between the other three clusters.

Research limitations/implications

Based on the bibliometric analysis and the systematic literature review, this study identifies relevant understudied topics and research gaps, which are suggested as future research directions.

Originality/value

This is the first study to systematise and discuss the literature concerning the relationship between big data and firm strategy.
Grey shade of work environment triad – effect of supervisor ostracism and perceived organizational obstruction on employees' behaviour: a moderated-mediation model
Authors: Akhtar Muhammad Waheed , Syed Fauzia , Javed Muzhar , Husnain Mudassir
Published: June 2020

Purpose

This study, based on the moderated-mediation model, investigates the indirect effect of facades of conformity in the relationship between supervisor ostracism and unethical work behaviour. Furthermore, this study tested the moderating role of perceived organizational obstruction in the aforementioned relationship through facades of conformity.

Design/methodology/approach

Employing a multi-wave and two-source data from employees and peers (n = 264) of the services sector in Pakistan, the authors tested the proposed framework using Hayes and Preacher moderated-mediation technique.

Findings

The findings reflect that supervisor ostracism encourages unethical behaviour at the workplace. Further, results revealed that facades of conformity mediated this direct relationship. Moreover, the authors found that perceived organizational obstruction moderated the relationship between supervisor ostracism and facades of conformity. Results also confirm that perceived organizational obstruction moderates the mediated relationship.

Research limitations/implications

The paper concludes with a discussion, managerial implications, limitations and directions for future research.

Originality/value

This study added value in the literature of supervisor ostracism, facades of conformity, unethical work behaviour and perceived organizational obstruction.
Does an oil boom promote firms’ R&D expenditure? Evidence from Ecuador
Authors: Grijalva Diego F. , Ponsetto Mary Lou , Pontón Yelitza
Published: June 2020

Purpose

The purpose of this paper is to examine how the expansionary phase of a business cycle driven by an exogenous commodity price shock (oil) affects R&D expenditures among Ecuadorian firms.

Design/methodology/approach

Using two rounds of the Ecuadorian National Science, Technology and Innovation Activities Survey (ACTI 2012 and 2015) and a data set on gross value added (GVA) by industry, we run a sample correction model applied to a panel data of 1,023 firms from 2009 to 2014.

Findings

In deciding whether to invest in R&D, the higher an industry’s GVA, the lower the predicted probability that firms in that industry would invest. Additionally, R&D investments are not procyclical, and there is marginal evidence that they might actually be countercyclical. These findings are consistent with Schumpeter (1939) and Ouyang (2011) and are likely due to an increased opportunity cost of R&D investment during the oil boom.

Originality/value

In this study, we examine a boom period and not a full business cycle. This boom is driven by an exogenous shock, deviating from much of the current literature, which focuses on endogenously driven business cycles. This paper examines how the oil shock impacted a variety of industries, and not just attractive ones. Additionally, this paper adds to the limited literature around R&D and business cycles in Latin America.
Blockchain-based applications in shipping and port management: a literature review towards defining key conceptual frameworks
Authors: Tsiulin Sergey , Reinau Kristian Hegner , Hilmola Olli-Pekka , Goryaev Nikolay , Karam Ahmed
Published: June 2020

Purpose

The purpose of this paper is to examine and to categorize the tendencies of blockchain-based applications in the shipping industry and supply chain as well as the interrelations between them, including possible correlation of found categories with theoretical background and existing concepts. This study also explores whether blockchain can be adopted into existing maritime shipping and port document workflow management.

Design/methodology/approach

The current study builds a conceptual framework through a systematic project review carried along with scientific and grey literature, published in journals and conference proceedings during the past decade and giving information or proposals on an issue.

Findings

The results showed that reviewed projects can be compiled into three main conceptual areas: document workflow management, financial processes and device connectivity. However, having clear interlinkages, none of the reviewed projects consider all three areas at once. Concepts associated with maritime document workflow received broad support among the reviewed projects. In addition, reviewed projects unintentionally follow the similar goals that were laid down within port management scientific projects before the introduction of blockchain technology.

Originality/value

This study contributes to research by revealing a consistent framework for understanding the blockchain applications within maritime port environment, a less-studied part of blockchain implementation in the supply chain field. Moreover, this work is the first to find out conceptual intersections and correlations between existing projects, mapping current tendencies and potentially increasing knowledge about the field.
A review of two psychological models in knowledge sharing: current trends and future agenda
Authors: Nguyen Tuyet-Mai
Published: June 2020

Purpose

Two psychological models, the theory of reasoned action (TRA) and the theory of planned behaviour (TPB) are the most common theories used to understand knowledge sharing behaviour. However, the empirical results are inconclusive on whether TRA and TPB can provide reasonable prediction of knowledge sharing attitude, intention and behaviour. Therefore, the purpose of this study is to conduct a review of these models in knowledge sharing.

Design/methodology/approach

This study reviews 63 papers to provide a comprehensive picture of these models in knowledge sharing.

Findings

Two main trends of modification were shown in the studies examining these models. Research gaps were identified as a guideline for future researchers to investigate potential moderators and examine these models from the participants’ perspective.

Originality/value

The model serves as a roadmap for future researchers and managers considering their strategy to enhance knowledge sharing.
Climate and soil micro‐organisms drive soil phosphorus fractions in coastal dune systems
Authors: García‐Velázquez Laura , Rodríguez Alexandra , Gallardo Antonio , Maestre Fernando T. , Dos Santos Everaldo , Lafuente Angela , Fernández‐Alonso María José , Singh Brajesh K. , Wang Jun‐Tao , Durán Jorge
Published: June 2020

The importance of soil phosphorus (P) is likely to increase in coming decades due to the growing atmospheric nitrogen (N) deposition originated by industrial and agricultural activities. We currently lack a proper understanding of the main drivers of soil P pools in coastal dunes, which rank among the most valued priority conservation areas worldwide.

Here, we evaluated the joint effects of biotic (i.e. microbial abundance and richness, vegetation and cryptogams cover) and abiotic (i.e. pH and aridity) factors on labile, medium‐lability and recalcitrant soil P pools across a wide aridity gradient in the Atlantic coast of the Iberian Peninsula.

Climate determined the availability of medium‐lability, recalcitrant and total P, but had a minor net effect on labile P, which was positively and significantly related to the presence of plants, mosses and lichens. Medium‐lability P was significantly influenced by soil bacterial richness and abundance (positively and negatively, respectively).

Our results suggest that micro‐organisms transfer P from medium‐lability pool to more labile one. At the same time, increases in bacterial richness associated to biofilms might be involved in the thickening of the medium‐lability P pool in our climosequence.

These bacterial‐mediated transfers would confer resistance to the labile P pool under future climate change and uncover an important role of soil micro‐organisms as modulators of the geochemical P cycle.
Temperature modulates compensatory responses to food limitation at metamorphosis in a marine invertebrate
Authors: Torres Gabriela , Giménez Luis
Published: June 2020

Under climate change, increased temperatures combined with food limitation may be critical for species with complex life cycles, if high growth rates characterize the larval development.

We studied the effect of increased temperature and food limitation on larval survival and on functional traits (developmental time, body mass, growth) at moulting and metamorphosis in the crab Carcinus maenas.

We followed the approach of models of metamorphosis integrating responses of body mass and developmental time to increased temperature and food limitation. We also evaluated if body mass decreased with temperature (according to the temperature‐size rule) and if developmental time followed an inverse exponential reduction (expected from some metabolic theories), as both trends are relevant for modelling effects of climate change on fitness and population connectivity.

Larvae produced by four females were reared separately from hatching to metamorphosis to the megalopa at two food conditions (ad libitum and food limitation), and at four temperatures covering the range experienced in the field (<20°C) and those expected from climate change (>20°C).

In general, body mass did not decrease with temperature, nor developmental time followed an inverse exponential response to temperature (under ad libitum food conditions).

At low temperatures (<20°C), food limitation resulted (in general) in small reductions in larval survival. Body mass and nitrogen content were little affected by food limitation while effects on carbon content were small. Increased developmental time partially or fully compensated for reduced growth rates. We interpreted this response as adaptive, as minimizing fitness costs associated to reduced body mass.

Increased temperatures (>20°C) exacerbated the effect of food limitation on mortality in larvae from three females. Developmental time was longer and larvae metamorphosed with reduced body mass, carbon and nitrogen content. Thus, compensatory responses failed and multiple fitness costs should be expected in individuals facing food limitation at increased temperatures.

We propose that integrative studies of traits at metamorphosis could be a basis to develop a mechanistic understanding of how species with complex life cycles will respond to climate change. Such models could eventually include hormonal and metabolic regulation of development as drivers of responses to environmental change.
Livestock grazing impacts components of the breeding productivity of a common upland insectivorous passerine: Results from a long‐term experiment
Authors: Malm Lisa E. , Pearce‐Higgins James W. , Littlewood Nick A. , Karley Alison J. , Karaszewska Ewa , Jaques Robert , Pakeman Robin J. , Redpath Stephen M. , Evans Darren M.
Published: June 2020

The intensity of pastoral management in areas of High Nature Value farming is declining in some regions of Europe but increasing in others. This affects open habitats of conservation concern, such as the British uplands, where bird species that benefit from low‐intensity grazing may be most sensitive to such polarization. While experimental manipulations of livestock grazing intensities have improved our understanding of upland breeding bird responses in the short term, none have examined the long‐term impacts of altered management on reproductive success.

Using a replicated landscape‐scale experiment that started in 2003, we investigated the effects of four grazing treatments (intensive sheep; low‐intensity sheep; low‐intensity mixed sheep and cattle; and no grazing) on the breeding productivity of meadow pipits Anthus pratensis, the most common upland passerine. Surveys were carried out systematically during early (2003 and 2004) and late (2015 and 2016) sampling periods of the experiment to compare the short‐ and long‐term effects of grazing treatments on breeding density and productivity of pipits specifically, but also on the overall bird community.

Pipit breeding density was lowest under low‐intensity sheep grazing while the highest egg‐stage nest survival was observed in the same treatment, although no significant treatment effects were detected on overall nest survival or fledgling output. There were no significant differences in treatment effects between the sampling periods on any breeding variable, but overall nest survival was lower in the later sampling period across all treatments.

Breeding bird species richness differed between treatments in the later sampling period, with highest species richness in the ungrazed treatment.

Synthesis and applications. Livestock grazing management can have different outcomes for different upland birds. Our results showed that, with time, meadow pipit breeding productivity tended to be higher when sheep grazing intensity was reduced and/or mixed with cattle, and lower when livestock were removed, but not significantly so. Removal of grazing, however, can significantly increase bird species richness. The long‐term experiment showed an overall decline in fledglings regardless of grazing treatments, potentially a result of increased predator numbers harboured by nearby developing woodland, highlighting the importance of considering wider landscape processes in grazing management decisions.
The Mechanisms Underlying the Intergenerational Transmission of Disadvantage: Three Examples from Australia
Authors: Vera‐Toscano Esperanza
Published: June 2020

The growing debate on the intergenerational transmission of disadvantage has refocused discussion on the factors that influence this intergenerational process. This study provides a short review of the central mechanisms underlying the intergenerational transmission of (dis)advantage and illustrates the importance of these mechanisms using findings from three recent studies undertaken in Australia using Australian household and administrative longitudinal data.
Intergenerational Mobility Research: Current Challenges and Future Directions
Authors: Mooi‐Reci Irma
Published: June 2020

This article discusses major challenges facing intergenerational mobility research in three main domains: (1) the (dis)connection between theory and empirical applications; (2) data gaps; and (3) measurement concerns. In doing so, it highlights theoretical and empirical extensions to better describe, explain and predict complex intergenerational transmission processes in the light of new and rapid administrative data linkages, more mature survey data and other forms of big data. The article concludes with future directions for research.
Visualising Time: A Compendium of Time Series Plots
Authors: Hirschberg Joe , Lye Jenny
Published: June 2020

Graphs are important for highlighting relationships within a data series or across several series. Modern computer software has provided flexibility in the construction of graphic displays that would have been impossible with the tools that were available to researchers only a few decades ago. This article illustrates a variety of different graphical presentations for time ordered or time series data that can now be constructed. These include time series plots, bar charts, range plots, radar charts, scatter plots, heat maps and seasonality plots. For each graph type presented, we discuss the best practice for their construction.
The Self‐Understanding of the Congolese Church during War: CENCO in the Grip of the Greatest Modern Humanitarian Crisis
Authors: Okitafumba Lokola Raphael
Published: June 2020

This article analyses how the National Conference of Congolese Catholic Bishops (CENCO) identified its public mission in society as veilleurs et éveilleurs des consciences (custodians and awakeners of consciences). This perception emerged because of external pressures, namely the phenomenon of war in the Democratic Republic of the Congo (DRC) in the late twentieth and early twenty‐first century. The argument is developed in four steps. First, I offer a succinct account of the period of war since 1996 and the magnitude of the havoc wreaked on the people of the DRC. Next, I consider the historical background of CENCO. Third, I discuss the organisation and some most important modern bishops of CENCO. Fourth, I analyse how CENCO perceived the role of the Catholic Church in this troubled society and how this acute consciousness emboldened the Congolese Catholic Church to tackle the woes of the deadliest war in recent history. Finally, I draw some implications and address challenges that CENCO faces when it intersects with politics.
Pre‐eclampsia‐like syndrome induced by severe COVID‐19: a prospective observational study
Authors: Mendoza M , Garcia‐Ruiz I , Maiz N , Rodo C , Garcia‐Manau P , Serrano B , Lopez‐Martinez RM , Balcells J , Fernandez‐Hidalgo N , Carreras E , Suy A
Published: June 2020

Objectives

To investigate the incidence of clinical, ultrasonographic and biochemical findings related to pre‐eclampsia (PE) in pregnancies with COVID‐19, and to assess their accuracy to differentiate between PE and the PE‐like features associated with COVID‐19.

Design

A prospective, observational study.

Setting

Tertiary referral hospital.

Participants

Singleton pregnancies with COVID‐19 at >20+0 weeks.

Methods

Forty‐two consecutive pregnancies were recruited and classified into two groups: severe and non‐severe COVID‐19, according to the occurrence of severe pneumonia. Uterine artery pulsatility index (UtAPI) and angiogenic factors (soluble fms‐like tyrosine kinase‐1/placental growth factor [sFlt‐1/PlGF]) were assessed in women with suspected PE.

Main outcome measures

Incidence of signs and symptoms related to PE, such as hypertension, proteinuria, thrombocytopenia, elevated liver enzymes, abnormal UtAPI and increased sFlt‐1/PlGF.

Results

Thirty‐four cases were classified as non‐severe and 8 as severe COVID‐19. Five (11.9%) women presented signs and symptoms of PE, all five being among the severe COVID‐19 cases (62.5%). However, abnormal sFlt‐1/PlGF and UtAPI could only be demonstrated in one case. One case remained pregnant after recovery from severe pneumonia and had a spontaneous resolution of the PE‐like syndrome.

Conclusions

Pregnant women with severe COVID‐19 can develop a PE‐like syndrome that might be distinguished from actual PE by sFlt‐1/PlGF, LDH and UtAPI assessment. Healthcare providers should be aware of its existence and monitor pregnancies with suspected pre‐eclampsia with caution.

Tweetable abstract

This study shows that a pre‐eclampsia‐like syndrome could be present in some pregnancies with severe COVID‐19.
Postmortem Changes of Female External Genitalia and Their Importance in Suspected Sexual Abuse
Authors: Al‐Saif Dalia M. , Al‐Farayedhi Maram A. , Al‐Shamsi Ghadah A. , Al‐Bayat Marwah I. , Almadani Osama M. , Kharoshah Magdy A.
Published: June 2020

Examination of the female external genitalia to assess for sexual abuse is performed in living individuals, and the interpretation of the findings is based on evidence‐based studies. However, in the deceased, no such studies are available, and postmortem changes could present as suspicious findings that can be mistaken for trauma. Patches of discoloration in the hymen were reported previously in one case as hypostasis (i.e., livor and lividity), and based on this finding, it was listed as a finding that is not associated with trauma. This was a retrospective study that was conducted in the Center of Forensic and Legal Medicine in Dammam, Saudi Arabia over a 4‐year period. The study included 30 deceased women in whom photographic documentation of their external genitalia was assessed for postmortem changes. The postmortem interval ranged from less than 24 h to more than 100 days, and the ages of these deceased women were in the 20–40 year‐old age group. In cases where the hymen, vagina, and/or fossa navicularis were clearly visible, none of these areas showed any hypostatic discoloration. A comparison between antemortem and postmortem appearance of the hymen in one case clearly showed the absence of hypostatic changes in the hymen. In conclusion, any discoloration of the external genitalia that is detected in a female decedent requires serious consideration.
Hydroxypropyl β‐cyclodextrin improving multiple stresses tolerance of Lactococcus lactis subsp. lactis
Authors: Cui Lianming , Lin Songyang , Yi Juanjuan , Liu Xin , Hao Limin , Ji Yizhi , Lu Laizheng , Ji Zhenyu , Kang Qiaozhen , Lu Jike
Published: June 2020

L. lactis is known as industrial starter in the fermentation of dairy and meat products, and it plays an important role in human health as an edible probiotic. During industrial production, L. lactis often experiences different stresses that delay the growth and decrease the survival in some serious conditions. In this study, the protective effects of hydroxypropyl β‐cyclodextrin (HP β‐CD) on L. lactis under multiple stresses were investigated. The microbial cells were treated with different stresses including heat, NaCl, cold, and H2O2 stresses, and the results were showed by measuring the OD600 or spot plating method. The growth and tolerance were improved when HP β‐CD was added during different stress conditions, better than that of trehalose. Besides, the scanning electron microscopic and fluorescence spectrum studies showed that HP β‐CD could combine with L. lactis to protect the cell structure, suggesting that HP β‐CD may act as a protective agent of L. lactis. Therefore, HP β‐CD could be considered as a potential protective agent to be applied in food industry, and its protective mechanism on L. lactis still needs further investigation.
Effects of superfine grinding on asparagus pomace. Part I: Changes on physicochemical and functional properties
Authors: Gao Wenjie , Chen Feng , Zhang Lianfu , Meng Qingran
Published: June 2020

The effects of superfine grinding on the physicochemical and functional properties of asparagus pomace were investigated. The results showed that in terms of the specific surface area, water solubility, soluble dietary fiber content, and ratio of insoluble dietary fiber to soluble dietary fiber, finer samples usually possessed better physicochemical properties compared with coarse samples. However, grinding samples excessively to produce small particle sizes could reduce the water‐holding capacity, oil‐binding capacity, and swelling capacity. In addition, the extraction of both free and bound phenolics in asparagus pomace powder samples and the samples’ absorption of both nitrite ion and glucose showed typical bell‐shaped curves, demonstrating that superfine grinding could significantly impact the various properties of asparagus pomace. This study should provide insights into the effect of micronization on the functionalities of fiber‐rich food materials.

Practical Application

This article deals with the effects of superfine grinding on the physicochemical and functional properties of asparagus pomace. The results showed that the properties of asparagus pomace did not always improve gradually with decreasing particle size. With a decrease in granularity, some parameters showed a bell‐shaped curve whereas others initially increased and then stabilized, indicating that in actual production, the crushing particle size should be determined according to actual needs or target parameters.
Safety of photosynthetic Synechococcus elongatus for in vivo cyanobacteria–mammalian symbiotic therapeutics
Authors: Williams Kiah M. , Wang Hanjay , Paulsen Michael J. , Thakore Akshara D. , Rieck Mary , Lucian Haley J. , Grady Frederick , Hironaka Camille E. , Chien Athena J. , Farry Justin M. , Shin Hye Sook , Jaatinen Kevin J. , Eskandari Anahita , Stapleton Lyndsay M. , Steele Amanda N. , Cohen Jeffrey E. , Woo Y. Joseph
Published: June 2020

The cyanobacterium Synechococcus elongatus (SE) has been shown to rescue ischaemic heart muscle after myocardial infarction by photosynthetic oxygen production. Here, we investigated SE toxicity and hypothesized that systemic SE exposure does not elicit a significant immune response in rats. Wistar rats intravenously received SE (n = 12), sterile saline (n = 12) or E. coli lipopolysaccharide (LPS, n = 4), and a subset (8 SE, 8 saline) received a repeat injection 4 weeks later. At baseline, 4 h, 24 h, 48 h, 8 days and 4 weeks after injection, clinical assessments, blood cultures, blood counts, lymphocyte phenotypes, liver function tests, proinflammatory cytokines and immunoglobulins were assessed. Across all metrics, SE rats responded comparably to saline controls, displaying no clinically significant immune response. As expected, LPS rats exhibited severe immunological responses. Systemic SE administration does not induce sepsis or toxicity in rats, thereby supporting the safety of cyanobacteria–mammalian symbiotic therapeutics using this organism.
Characteristics of patients with temporomandibular joint osteoarthrosis on magnetic resonance imaging
Authors: Toshima Hiroo , Ogura Ichiro
Published: June 2020

Introduction

Temporomandibular joint (TMJ) dysfunction is a common condition that is best evaluated with magnetic resonance (MR) imaging. The aim of this study was to investigate the characteristics of the patients with TMJ osteoarthrosis on MR imaging.

Methods

The MR images of 206 TMJs of 103 patients with temporomandibular disorders (TMD) were evaluated retrospectively in this study. The relationship between osteoarthrosis and age, gender, TMJ pain and MR imaging findings, such as disc displacement with or without reduction and TMJ effusion, was analysed.

Results

The patients with TMJ osteoarthrosis (mean: 51.6 years) were significantly older than those without osteoarthrosis (mean: 44.8 years, P = 0.027). The incidence of the patients with TMJ osteoarthrosis was significantly different between with (10.0 %) and without reduction (57.0 %, P < 0.001). Logistic multivariate regression analysis demonstrated that disc displacement without reduction was significant in patients with TMJ osteoarthrosis (odds ratio = 12.285, P < 0.001).

Conclusions

This study suggests that characteristics of the patients with TMJ osteoarthrosis on MR imaging include older and disc displacement without reduction.
A comparative study of PF‐06438179/GP1111 (an infliximab biosimilar) and reference infliximab in patients with moderate to severe active rheumatoid arthritis: A subgroup analysis
Authors: Kameda Hideto , Uechi Eishi , Atsumi Tatsuya , Abud‐Mendoza Carlos , Kamei Kazumasa , Matsumoto Tsugumi , Ponce de Leon Dario , Rehman Muhammad I. , Zhang Min , Radominski Sebastiao C.
Published: June 2020

Aim

PF‐06438179/GP1111 (PF‐SZ‐IFX) is a biosimilar of reference infliximab (Remicade®). This analysis compared the efficacy of PF‐SZ‐IFX and reference infliximab sourced from the European Union (IFX‐EU) in patient subgroups from a randomized, comparative study of PF‐SZ‐IFX versus IFX‐EU.

Methods

Patients with rheumatoid arthritis were randomized 1:1 to PF‐SZ‐IFX (n = 324) or IFX‐EU (n = 326); study drug (3 mg/kg) was administered intravenously at weeks 0, 2, and 6, then every 8 weeks thereafter. Subgroup analyses of efficacy endpoints such as American College of Rheumatology criteria for ≥20% clinical improvement (ACR20), change in high‐sensitivity C‐reactive protein (hs‐CRP), and change in Disease Activity Score in 28 joints, four components based on hs‐CRP (DAS28‐CRP) at weeks 14 and 30 were performed by age, gender, race, region, immunogenicity status, and treatment history.

Results

Overall, ACR20 response rates as well as changes in DAS28‐CRP and hs‐CRP at week 14 were similar between PF‐SZ‐IFX and IFX‐EU within the subgroups of age, gender, race, region, treatment history, and immunogenicity status. Results to week 30 support overall similarity in efficacy between the two treatment arms in all subgroups.

Conclusion

Overall, PF‐SZ‐IFX and IFX‐EU were similar in efficacy within the analyzed subgroups of age, gender, race, region, treatment history, and immunogenicity status. The efficacy results from these subgroup analyses were aligned with the previously described results for the overall population up to week 30.
Tofacitinib in the treatment of Indian patients with rheumatoid arthritis: A post hoc analysis of efficacy and safety in Phase 3 and long‐term extension studies over 7 years
Authors: Chopra Arvind , Shobha Vineeta , Chandrashekara Srikantiah , Veeravalli Sarath C. M. , Sharma Reena , Rao Uppuluri R. , Pandya Sapan , Wagh Shrikant , Kadel Jugal K. , Thorat Amit V. , Adhav Charles , Santos Estrella Paul , Yu Wei , Kwok Kenneth , Wouters Ann
Published: June 2020

Objectives

Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We characterized tofacitinib efficacy/safety in Indian vs rest of the world (ROW; excluding India) RA patients.

Methods

Efficacy data were pooled for disease‐modified antirheumatic drug (DMARD) inadequate responders from Phase (P)3 studies. For Indian patients, ORAL Solo and ORAL Scan; ROW (excluding India), these studies plus ORAL Step, ORAL Sync, and ORAL Standard. Safety data also included ORAL Start (P3; methotrexate‐naïve) and ORAL Sequel (long‐term extension [LTE] study; data cut‐off March 2017) for Indian patients, and these studies plus A3921041 (LTE study; Japanese study) for ROW. Efficacy outcomes at months 3/6: American College of Rheumatology (ACR)20/50/70; Disease Activity Score in 28 joints, erythrocyte sedimentation rate remission/low disease activity; change from baseline in Health Assessment Questionnaire‐Disability Index. Incidence rates (IRs; patients with events/100 patient‐years) for adverse events of special interest (AESIs) were assessed throughout. Descriptive data underwent no formal comparison.

Results

One‐hundred‐and‐ninety‐seven Indian and 3879 ROW patients were included. Compared with ROW patients, Indian patients were younger, had lower body mass index, shorter RA duration, and higher baseline disease activity; most Indian patients were non‐smokers and all were biologic DMARD (bDMARD)‐naïve. Month 3 ACR20 rates with tofacitinib 5 mg twice daily/10 mg twice daily/placebo were 67.4%/82.1%/40.9% (India) and 59.0%/66.1%/28.2% (ROW), and month 6 rates were 76.2%/92.1%/88.9% (India) and 69.0%/74.2%/66.5% (ROW). Month 3/6 improvements in other outcomes were generally numerically greater with tofacitinib vs placebo, and similar in both populations. Compared with ROW, Indian patients had numerically fewer AEs/serious AEs, and similar IRs for discontinuations due to AEs and AESIs, except that tuberculosis (TB) IR was higher in Indian (IR = 1.21; 95% CI 0.49, 2.49) vs ROW patients (IR = 0.17; 95% CI 0.11, 0.25).

Conclusions

Tofacitinib efficacy/safety were similar in both populations, except TB IR, which was higher in Indian patients but in line with those in bDMARD‐treated RA patients from high‐risk countries (IR = 0.00‐2.56; TB IR >0.05 [World Health Organization]). Limitations included the small Indian population and baseline differences between populations.
Prevention and treatment of suspected pneumonia in Ethiopian children less than five years from household to primary care
Authors: Tariku Amare , Okwaraji Yemisrach B. , Worku Alemayehu , Biks Gashaw Andargie , Åke Persson Lars , Berhane Yemane
Published: June 2020

Aim

Ethiopia has implemented the integrated community case management to reduce mortality in childhood diseases. We analysed prevention, care seeking and treatment of suspected pneumonia from household to health facility in Ethiopia.

Methods

Analyses were based on a survey in four regions that included modules covering 5714 households, 169 health posts with 276 health extension workers and 155 health centres with 175 staff. Caregivers of children aged 2‐59 months responded to questions on awareness of services and care seeking for suspected pneumonia. Pneumonia‐related knowledge of health workers was assessed.

Results

When a child had suspected pneumonia, 46% (95% CI: 25,68) sought care at health facilities, and 27% (95% CI: 12,51) received antibiotics. Forty‐one per cent had received full immunisation. One‐fifth (21%, 95%: 19,22) of the caregivers were aware of pneumonia treatment. Sixty‐four per cent of the health extension workers correctly mentioned fast or difficult breathing as signs of suspected pneumonia, and 88% suggested antibiotics treatment.

Conclusion

The caregivers' awareness of suspected pneumonia treatment and the utilisation of these services were low. Some of the health extension workers were not knowledgeable about suspected pneumonia. Strengthening primary health care, including immunisation, and enhancing the utilisation of services are critical for further reduction of pneumonia mortality.
Activated FMS‐like tyrosine kinase 3 ameliorates angiotensin II‐induced cardiac remodelling
Authors: Ma Wenzhuo , Liang Fanfan , Zhan Heqin , Jiang Xixi , Gao Chenying , Zhang Xin , Zhang Kaina , Sun Qiang , Hu Hao , Zhao Zhenghang
Published: June 2020

Aim

FMS‐like receptor tyrosine kinase 3 (Flt3) has been reported to be increased in cardiomyocytes responding to ischaemic stress. This study was to determine whether Flt3 activation could ameliorate pressure overload‐induced heart hypertrophy and fibrosis, and to elucidate the mechanisms of action.

Methods

In vivo cardiac hypertrophy and remodelling experiments were conducted by infusing angiotensin II (Ang II) chronically in male C57BL/6 mice. Flt3‐specific ligand (FL) was administered intraperitoneally every two days (5 µg/mouse). In vitro experiments on hypertrophy, apoptosis and autophagy mechanism were performed in neonatal rat cardiomyocytes (NRCMs) and H9c2 cells with adenovirus vector‐mediated overexpression of Flt3.

Results

Our results demonstrated that following chronic Ang II infusion for 4 weeks, the mice exhibited heart hypertrophy, fibrosis, apoptosis and contractile dysfunction. Meanwhile, Ang II induced autophagic responses in mouse hearts, as evidenced by increased LC3 II and decreased P62 expression. These pathological alterations in Ang II‐treated mice were significantly ameliorated by Flt3 activation with FL administration. In NRCMs and Flt3‐overexpressed H9c2 cells, FL attenuated Ang II‐induced pathological autophagy and inactivated AMPK/mTORC1/FoxO3a signalling, thereby efficiently mitigating cell hypertrophy and apoptosis. Conversely, the AMPK activator metformin or the mTORC1 inhibitor rapamycin reversed the effects of FL on the alterations of autophagy, hypertrophy and apoptosis in cardiomyocytes induced by Ang II.

Conclusion

Flt3 activation ameliorates cardiac hypertrophy, fibrosis and contractile dysfunction in the mouse model of chronic pressure overload, most likely via suppressing AMPK/mTORC1/FoxO3a‐mediated autophagy. These results provide new evidence supporting Flt3 as a novel therapeutic target in maladaptive cardiac remodelling.
Reducing dropout in acceptance and commitment therapy, mindfulness‐based cognitive therapy, and problem‐solving therapy for chronic pain and cancer patients using motivational interviewing
Authors: Malins Sam , Biswas Sanchia , Rathbone James , Vogt William , Pye Naomi , Levene Jo , Moghaddam Nima , Russell John
Published: June 2020

Objective

Acceptance and commitment therapy, mindfulness‐based cognitive therapy, and problem‐solving therapy are types of cognitive‐behavioural therapy (CBT) group that improve physical and mental health in chronic pain or cancer. However, dropout is high due to group demands alongside physical impairments. Motivational interviewing (MI) is a well‐evidenced means of enhancing treatment adherence. Few studies have investigated MI as an adjunct to CBT in cancer or chronic pain, and none have established the minimum MI duration required for adherence improvement. This study evaluated minimal‐duration MI to improve adherence in three CBT group types for cancer and chronic pain.

Methods

In a cohort study of 99 cancer and chronic pain patients, 47 were given a 10‐ to 15‐min structured MI telephone intervention (MI‐call) after the first session. The remaining 52 received a CBT group without MI (no‐MI).

Results

Odds of completing group CBTs were five times greater for patients in the MI‐call cohort versus no‐MI. Effects remained when controlling for age, gender, diagnosis, group type, and baseline quality of life. The MI‐call cohort attended one extra session per patient compared to no‐MI, controlling for age, gender, and diagnosis.

Conclusions

A brief MI telephone intervention may improve adherence to group CBTs in cancer and chronic pain.

Practitioner points

A brief motivational interviewing (MI) telephone intervention may reduce dropout from group cognitive‐behavioural therapies (CBTs) for cancer and chronic pain patients when administered after the first group session in routine care.

Recipients of this intervention were five times more likely to complete a group CBT programme than those who did not receive it.

Therefore, a minimal‐dose MI intervention can have clinically important effects on dropout in group CBTs for patients with long‐term conditions.

It is unclear whether this intervention would also result in greater outcome improvements.
Platelet hyperactivation in multiple myeloma is also evident in patients with premalignant monoclonal gammopathy of undetermined significance
Authors: O’Sullivan Leanne R. , Meade‐Murphy Gerardene , Gilligan Oonagh M. , Mykytiv Vitaliy , Young Paul W. , Cahill Mary R.
Published: June 2020

Thrombotic events are common in patients with multiple myeloma (MM), smouldering myeloma (SM) and monoclonal gammopathy of undetermined significance (MGUS). Previous studies have indicated platelet hyperactivation as a feature of thrombotic risk in MM, but there is a dearth of data in MGUS. In the present study, multiparameter analysis of platelet activation and responsiveness was investigated by flow cytometry in patients with MGUS, SM/MM and healthy controls (HCs). The median platelet surface CD63 levels, annexin V and PAC‐1 antibody (specific for activated integrin αIIbβ3) binding were significantly elevated in patients with MGUS versus the HCs. These markers were also elevated in SM/MM, but not significantly. In all, 74% of MGUS and 38% of SM/MM patients had one or more elevated marker of platelet activation, compared to 19% of the HCs. Marker‐specific hyporesponsiveness of platelets to agonist [adenosine diphosphate (ADP), thrombin receptor‐activating peptide 6] stimulation in vitro was observed, with significantly reduced surface levels of P‐selectin in response to ADP in patients with MGUS. Platelet‐leucocyte aggregates were not altered in patients, while platelet‐associated immunoglobulins were elevated in a subset of patients. Overall, we found that platelet hyperactivation is prevalent in both MGUS and SM/MM patients and is potentially related to hyporesponsiveness. These observations suggest that further investigation of the predictive and prognostic value of platelet hyperactivation in such patients is warranted.
Challenges in the management of patients with systemic light chain (AL) amyloidosis during the COVID‐19 pandemic
Authors: Kastritis Efstathios , Wechalekar Ashutosh , Schönland Stefan , Sanchorawala Vaishali , Merlini Giampaolo , Palladini Giovanni , Minnema Monique , Roussel Murielle , Jaccard Arnaud , Hegenbart Ute , Kumar Shaji , Cibeira Maria T. , Blade Joan , Dimopoulos Meletios A.
Published: June 2020

The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2)‐associated coronavirus disease 2019 (COVID‐19) is primarily manifested as a respiratory tract infection, but may affect and cause complications in multiple organ systems (cardiovascular, gastrointestinal, kidneys, haematopoietic and immune systems), while no proven specific therapy exists. The challenges associated with COVID‐19 are even greater for patients with light chain (AL) amyloidosis, a rare multisystemic disease affecting the heart, kidneys, liver, gastrointestinal and nervous system. Patients with AL amyloidosis may need to receive chemotherapy, which probably increases infection risk. Management of COVID‐19 may be particularly challenging in patients with AL amyloidosis, who often present with cardiac dysfunction, nephrotic syndrome, neuropathy, low blood pressure and gastrointestinal symptoms. In addition, patients with AL amyloidosis may be more susceptible to toxicities of drugs used to manage COVID‐19. Access to health care may be difficult or limited, diagnosis of AL amyloidosis may be delayed with detrimental consequences and treatment administration may need modification. Both patients and treating physicians need to adapt in a new reality.