bluuebunny/crossref_metadata_2025 huggingface dataset:
Voice or silence: antecedents of whistleblowing intentions
Authors: Iwai Tatiana , Yeung Luciana , Artes Rinaldo
Published: March 2021

Purpose

This study aims to examine the effects of peer ethical behavior and individual differences in valuation of fairness vs loyalty on whistleblowing intentions in academic settings. This study also tests the underlying mechanism responsible for the effects of peer behavior on reporting intentions, namely, fear of reprisal.

Design/methodology/approach

A survey was conducted with 947 undergraduate students. The model was tested using ordinary least squares regression models followed by bootstrapped mediation analyses.

Findings

Results showed that the effects of peer ethical behavior on whistleblowing intentions are mediated by fear of retaliation. Moreover, the findings indicated that, for low-severity transgressions, there is an interactive effect between fear of retaliation and endorsement of fairness over loyalty on whistleblowing intentions.

Research limitations/implications

When the misconduct is seen as minor, a potential whistleblower may understand that the expected costs outweigh the possible benefits of blowing the whistle. In such situations, higher fear of retaliation would undermine the effects of individual’s endorsement of fairness over loyalty on reporting intentions.

Practical implications

As the social environment significantly affects someone’s whistleblowing intentions, there should be visible efforts to improve and to foster an ethical infrastructure in organizations.

Social implications

As fear of retaliation by peers is one of the most important determinants affecting the decision to report misconduct in general, there must be serious efforts from leaders to mitigate any threat of retaliation to those who come forward.

Originality/value

This work contributes to the discussion about individual and situational antecedents of whistleblowing. More importantly, it sheds light on one potential boundary condition for the influence of the fairness–loyalty tradeoff on whistleblowing decisions: severity of the transgression. The findings provide initial evidence that, for low-severity transgressions, fear of retaliation weakens the positive effects of one’s moral compass in terms of preference for fairness over loyalty on whistleblowing intentions.
AccountAbility’s AA1000AP standard: a framework for integrating sustainability into organisations
Authors: Farooq Muhammad Bilal , Zaman Rashid , Nadeem Muhammad
Published: March 2021

Purpose

This study aims to evaluate corporate sustainability integration by evaluating corporate practices against the sustainability principles of inclusivity, materiality, responsiveness and impact outlined in AccountAbility’s AA1000 Accountability Principles (AA1000AP) standard.

Design/methodology/approach

Data comprise 12 semi-structured interviews with senior managers of listed New Zealand companies. Findings are evaluated against AccountAbility’s principles of inclusivity, materiality, responsiveness and impact, which are based on a normative view of stakeholder theory.

Findings

In terms of inclusivity, stakeholder engagement is primarily monologic and is directed more towards traditional stakeholder groups. However, social media, which is gaining popularity, has the potential to facilitate greater dialogic stakeholder engagement. While most companies undertake a materiality assessment (with varying degrees of rigour) to support sustainability reporting, only some use it to drive planning and decision-making. Companies demonstrate responsiveness to stakeholder concerns through corporate governance and sustainability initiatives. Companies are monitoring and measuring their impact on stakeholders using sustainability key performance indicators (KPIs). However, measuring traditional metrics is easier than measuring areas such as the community. In rare instances, the executive’s remuneration is linked to these sustainability KPIs.

Practical implications

The study findings offer useful examples of the integration of sustainability into corporate processes and systems. Practitioners may find the insights useful in understanding how sustainability is currently being integrated into corporate practices by best practice New Zealand companies. Regulators may consider incorporating AA1000AP into their corporate governance guidelines. Finally, academics may find the study useful for teaching business and accounting courses and to guide the next generation of business managers.

Originality/value

First, the study brings together four streams of research on how sustainability reports are prepared (inclusivity, materiality, responsiveness and impact) in a single study. Second, the findings offer novel insights by evaluating corporate sustainability against the requirements of a standard that has received little academic attention.
Identification of genes required for gold and silver tolerance in Burkholderia cenocepacia H111 by transposon sequencing
Authors: Gualdi Stefano , Agnoli Kirsty , Vitale Alessandra , Higgins Steven , Eberl Leo
Published: March 2021

Members of the genus Burkholderia show remarkable abilities to adapt to a wide range of environmental conditions and is frequently isolated from soils contaminated with heavy metals. In this study, we used a transposon sequencing approach to identify 138 and 164 genes that provide a benefit for growth of the opportunistic pathogen Burkholderia cenocepacia H111 in the presence of silver and gold ions respectively. The data suggest that arginine metabolism and citrate biosynthesis are important for silver tolerance, while components of an ABC transporter (BCAL0307‐BCAL0308) and de novo cysteine biosynthesis are required for tolerance to gold ions. We show that determinants that affect tolerance to both metal ions include the two‐component systems BCAL0497/99 and BCAL2830/31 and genes that are involved in maintaining the integrity of the cell envelope, suggesting that membrane proteins represent important targets of silver and gold ions. Furthermore, we show that that the P‐type ATPase CadA (BCAL0055), which confers tolerance to cadmium contributes to silver but not gold tolerance. Our results may be useful for improving the antibacterial effect of silver and gold ions to combat drug‐resistant pathogens.
Understanding the secondary supply of alcohol as a wicked policy problem: The unique case of the Banned Drinker Register in the Northern Territory
Authors: Adamson Elizabeth , Smith James A. , Clifford Sarah , Wallace Tessa
Published: March 2021

In an effort to tackle the exceptionally high level of alcohol consumption in the Northern Territory (NT) of Australia, there are a suite of alcohol policies and new legislation that have been introduced. These include restricted purchasing and consumption for certain individuals. In 2017, the Banned Drinker Register (BDR) was (re)introduced – a policy that involves placing persons who consume alcohol at harmful levels to themselves or others onto a register which prohibits the purchase of alcohol from take‐away liquor outlets. As a result, there is an incentive for banned drinkers to obtain alcohol through friends, family, and through the black market – referred to as secondary supply. Though the phenomenon of secondary supply is not new, the recent evaluation of the BDR highlighted a number of challenges of tackling the secondary supply of alcohol. Informed by Head's framework for assessing ‘wicked’ policy problems, this policy analysis uses data from interviews with stakeholders undertaken as part of two studies on alcohol policy and services. The findings present the limitations of the policy design and implementation context in preventing secondary supply of alcohol to banned drinkers. The paper concludes with implications for policy and research that better recognise the implementation context.
Understanding recent HECS–HELP price misunderstandings
Authors: Chapman Bruce , Khemka Gaurav
Published: March 2021

In October 2020, the Australian Parliament legislated what appear to be significant changes in HECS–HELP prices, the tuition charges levied on domestic undergraduate students. Through this policy change, the Government aims to influence student choices in order to help deliver the skill changes presumed to be required for the economy's post‐COVID make‐up. This paper examines, in conceptual and empirical terms, a key aspect of the motivation for the reform, the true meaning of prices in the HECS–HELP world of an income‐contingent loan (ICL). We explain the conceptual basis of ICL charges and, with 2016 Census data, illustrate the meaning of the price changes between disciplines, by gender, and for a suite of expected future graduate lifetime income distributions. Our analysis points strongly to the conclusion that the true price changes are far less than they appear to be, highlighting the potential of there being quite muted consequences for student discipline choices.
Diversification, Khashoggi, and Saudi Arabia’s Public Investment Fund
Authors: McPherson‐Smith Oliver
Published: March 2021

Despite the sizeable economic clout of Saudi Arabia’s Public Investment Fund (PIF), the academic literature on the PIF is relatively nascent. How do domestic and international political considerations shape the PIF’s investment policies? This article contends that the PIF’s current domestic investments constitute the latest incarnation of an historic pattern of development policies in Saudi Arabia. This pattern challenges the PIF with balancing market‐driven development and satiating the preferences of political leaders. Meanwhile, the PIF’s international investments are subject to a novel form of political risk. While international political risk has previously emanated from public regulation and oversight, the Khashoggi incident has given rise to unparalleled private sector‐led, non‐regulatory political risk. For other sovereign wealth funds, the PIF’s experience is indicative of potential future non‐regulatory political risk in western markets. By using the PIF as a case study to explore how domestic and international factors influence the behavior of a sovereign wealth fund (SWF), this article contributes to a growing literature on the non‐economic drivers of SWF investments.
The capacity of neurological pupil index to predict absence of somatosensory evoked potentials after cardiac arrest—A study protocol
Authors: Lilja Linus , Thuccani Meena , Joelsson Sara , Nilsson Josefin , Redfors Petra , Lundgren Peter , Rylander Christian
Published: March 2021

Background

Anoxic‐ischemic brain injury is the most common cause of death after cardiac arrest (CA). Robust methods to detect severe injury with a low false positive rate (FPR) for poor neurological outcome include the pupillary light reflex (PLR) and somatosensory evoked potentials (SSEP). The PLR can be assessed manually or with automated pupillometry which provides the neurological pupil index (NPi). We aim to describe the interrelation between NPi values and the absence of SSEP cortical response and to evaluate the capacity of NPi to predict the absence of cortical SSEP response in comatose patients after CA.

Methods

A total of 50 patients will be included in an explorative, prospective, observational study of adult (>18 years) comatose survivors of CA admitted to intensive care in a university hospital. NPi assessed with a hand‐held pupillometer will be compared to SSEP signals recorded >48 hours after CA. Primary outcomes are sensitivity, specificity, and odds ratio for NPi to predict bilateral absence of the SSEP N20 signal, with NPi values corresponding to <5% FPRs of SSEP absence. Secondary outcomes are the PLR and SSEP sensitivity, specificity, and odds ratio for poor neurological outcome at hospital discharge and death at 30 days.

Discussion

The PLR and SSEP may have a systematic interrelation, and a certain NPi threshold could potentially predict the absence of cortical SSEP response. If this can be concluded from the present study, SSEP testing could be excluded in certain patients to save resources in the multimodal prognostication after CA.

Editorial comment

The interrelation between loss of the pupillary light reflex (PLR) and the loss of cortical response to a somatosensory evoked potential (SSEP) in comatose cardiac arrest patients is not known. This exploratory prospective study is designed to evaluate whether a specific degree of attenuated PLR, as measured by semiautomated pupillometry, can predict the bilateral loss of cortical SSEP response in severe anoxic/ischemic brain injury. Such an interrelation between the two methods would enable the use of pupillometry rather than the more resource demanding SSEP for neurologic prognostication in post cardiac arrest patients.

Trial registration

ClinicalTrials.gov, NCT04720482, Registered 21 January 2021, retrospectively registered.
Safety and efficacy of an oral misoprostol standard‐dose regimen vs a low‐dose regimen for induction of labour in Papua New Guinean women: An open‐label randomised controlled trial
Authors: Bolnga John W. , Mola Glen D. L. , Totona Catherine , Ao Paula , Lufele Elvin , Laman Moses
Published: March 2021

Background

Oral misoprostol is widely used for induction of labour (IOL) in developing countries because of its many advantages. However, limited data exist concerning its safety and efficacy when lower doses are used.

Aim

To determine the safety and efficacy of a low‐dose oral misoprostol regimen (commencing at 12 μg) compared to a standard‐dose regimen (commencing at 25 μg) in Papua New Guinea (PNG) women undergoing IOL.

Materials and Methods

This was an open‐label non‐inferiority randomised controlled trial conducted at a provincial hospital in PNG. Women with singleton pregnancies ≥36 weeks with cephalic presentation and a Bishops score of <6, requiring IOL were enrolled. Both regimens were incremented second‐hourly to a maximum required dose within 24 h or until commencement of labour. The primary outcome was the proportion of women who delivered within 24 h of drug administration without any severe adverse events.

Results

Of the 262 women induced (130 standard‐dose vs 132 low‐dose), rates of successful induction were high for both regimens (120/130 (92%) vs 118/132 (89%); P = 0.52). Fourteen women (11%) in the standard‐dose regimen and 20 (15%) in the low‐dose regimen had severe adverse events. There was no significant difference in the safety profile of the two regimens (106/130 (82%) vs 98/132 (74%); P = 0.18). The induction‐to‐delivery time was significantly shorter in the standard‐dose arm (15.2 ± 8.7 h vs 18.0 ± 9.1 h; P = 0.01).

Conclusion

The standard‐dose regimen for IOL has greater efficacy in reducing induction‐to‐delivery time compared to the low‐dose regimen. There was no significant difference in the number of adverse events between the two regimens.
A pilot study of short‐term hemodynamic effects of negative pressure ventilation in chronic obstructive pulmonary disease assessed using electrical cardiometry
Authors: Chao Ke‐Yun , Nassef Yasser
Published: March 2021

Background

Pulmonary rehabilitation combined with negative pressure ventilation (NPV) demonstrated benefits in patients with chronic obstructive pulmonary disease (COPD). The effect of NPV remains unknown. This study aims to clarify the short‐term response of the hemodynamic outcome of NPV in patients with COPD undergoing pulmonary rehabilitation program by electrical cardiometry.

Methods

This is an observational retrospective study of COPD patients who had been treated in a pulmonary rehabilitation unit with NPV between January 2018 and December 2019 that were enrolled to analyze the hemodynamic outcomes.

Results

Thirty patients with COPD that were undergoing a pulmonary rehabilitation program and were regularly receiving NPV were enrolled. Cardiac output (p < .001) and heart rate (p < .001) showed a significant decrease after NPV. Stroke volume did not demonstrate significant change (p = .15). There was a significant decrease in thoracic fluid content (p = .016) and a significant increase in stroke volume variation (p = .038) systemic vascular resistance (p < .001) and left ventricular ejection time (p < .001). Other hemodynamic parameters were all comparable before and after NPV.

Conclusions

Negative pressure ventilation demonstrated an impact on hemodynamics in patients with chronic obstructive pulmonary disease undergoing pulmonary rehabilitation. Electrical cardiometry is a feasible method of determining the hemodynamic effects of negative pressure ventilation. Thoracic fluid content significantly decreased immediately after the NPV.
Optimal pin position in supraacetabular external fixation
Authors: Krassnig Renate , Hohenberger Gloria M. , Schimmerl Paul , Schwarz Angelika , Pichler Wolfgang , Puchwein Paul , Wildburger Renate
Published: March 2021

Background

This study focuses on (i) the length of the intraosseous part of the supraacetabular pin using the insertion technique from the spina iliaca anterior inferior to the cortical part of the incisura ischiadica major, (ii) the angle of insertion of the supraacetabular pin in the transversal plane and (iii) gender‐specific differences of the measured results.

Methods

Images of uninjured pelves from 49 patients (64‐line computed tomography scanner) were evaluated, and virtual external fixator pins were positioned using a three‐dimensional reconstructions of computed tomography scans. The length of the pins and the insertion angle were investigated. Descriptive statistics were used, and gender‐specific differences were calculated. A P‐value of <0.05 was considered statistically significant.

Results

The results showed significant differences between male and female pelves concerning both pin length and insertion angel. For male pelves, the mean screw length was 82.7 mm (SD 5.1; range 72.9–94.3). For females, this was statistically significantly shorter (P ≤ 0.001), with an average of 74.1 mm (SD 5.0; range 63.1–81.9). In the male subgroup, the insertion angle was a mean of 22.6° (SD 3.4; range 12.4–31.8), and the female pelves had an average angle of 19.7° (SD 4.0; range 11.7–24.5). These values differed statistically significantly (P = 0.0032).

Conclusion

Based on our measurements, we can confirm that both the length of the Schanz screws and the angle of insertion for the supraacetabular external fixator show a statistically significant difference between males and females.
Novel knock‐in mouse model for the evaluation of the therapeutic efficacy and toxicity of human podoplanin–targeting agents
Authors: Ukaji Takao , Takemoto Ai , Shibata Harumi , Kakino Mamoru , Takagi Satoshi , Katayama Ryohei , Fujita Naoya
Published: March 2021

Podoplanin is a key molecule for enhancing tumor‐induced platelet aggregation. Podoplanin interacts with CLEC‐2 on platelets via PLatelet Aggregation–inducing domains (PLAGs). Among our generated antibodies, those targeting the fourth PLAG domain (PLAG4) strongly suppress podoplanin–CLEC‐2 binding and podoplanin‐expressing tumor growth and metastasis. We previously performed a single‐dose toxicity study of PLAG4‐targeting anti‐podoplanin–neutralizing antibodies and found no acute toxicity in cynomolgus monkeys. To confirm the therapeutic efficacy and toxicity of podoplanin‐targeting antibodies, a syngeneic mouse model that enables repeated dose toxicity tests is needed. Replacement of mouse PLAG1‐PLAG4 domains with human homologous domains drastically decreased the platelet‐aggregating activity. Therefore, we searched the critical domain of the platelet‐aggregating activity in mouse podoplanin and found that the mouse PLAG4 domain played a critical role in platelet aggregation, similar to the human PLAG4 domain. Human/mouse chimeric podoplanin, in which a limited region containing mouse PLAG4 was replaced with human homologous region, exhibited a similar platelet‐aggregating activity to wild‐type mouse podoplanin. Thus, we generated knock‐in mice with human/mouse chimeric podoplanin expression (PdpnKI/KI mice). Our previously established PLAG4‐targeting antibodies could suppress human/mouse chimeric podoplanin–mediated platelet aggregation and tumor growth in PdpnKI/KI mice. Repeated treatment of PdpnKI/KI mice with antibody‐dependent cell‐mediated cytotoxicity activity–possessing PG4D2 antibody did not result in toxicity or changes in hematological and biochemical parameters. Our results suggest that anti‐podoplanin–neutralizing antibodies could be used safely as novel anti‐tumor agents. Our generated PdpnKI/KI mice are useful for investigating the efficacy and toxicity of human podoplanin–targeting drugs.
Evaluating unintended consequences of intentional species introductions and eradications for improved conservation management
Authors: Pearson Dean E. , Clark Tyler J. , Hahn Philip G.
Published: March 2021

Increasingly intensive strategies to maintain biodiversity and ecosystem function are being deployed in response to global anthropogenic threats, including intentionally introducing and eradicating species via assisted migration, rewilding, biological control, invasive species eradications, and gene drives. These actions are highly contentious because of their potential for unintended consequences. We conducted a global literature review of these conservation actions to quantify how often unintended outcomes occur and to elucidate their underlying causes. To evaluate conservation outcomes, we developed a community assessment framework for systematically mapping the range of possible interaction types for 111 case studies. Applying this tool, we quantified the number of interaction types considered in each study and documented the nature and strength of intended and unintended outcomes. Intended outcomes were reported in 51% of cases, a combination of intended outcomes and unintended outcomes in 26%, and strictly unintended outcomes in 10%. Hence, unintended outcomes were reported in 36% of all cases evaluated. In evaluating overall conservations outcomes (weighing intended vs. unintended effects), some unintended effects were fairly innocuous relative to the conservation objective, whereas others resulted in serious unintended consequences in recipient communities. Studies that assessed a greater number of community interactions with the target species reported unintended outcomes more often, suggesting that unintended consequences may be underreported due to insufficient vetting. Most reported unintended outcomes arose from direct effects (68%) or simple density‐mediated or indirect effects (25%) linked to the target species. Only a few documented cases arose from more complex interaction pathways (7%). Therefore, most unintended outcomes involved simple interactions that could be predicted and mitigated through more formal vetting. Our community assessment framework provides a tool for screening future conservation actions by mapping the recipient community interaction web to identify and mitigate unintended outcomes from intentional species introductions and eradications for conservation.
England’s municipal waste regime: Challenges and prospects
Authors: Gregson Nicky , Forman Peter J.
Published: March 2021

This paper provides a synthetic account of England’s municipal waste regime at the end of the 2010s. In technical‐material terms, the regime, previously heavily dependent upon landfill, is now characterised by energy‐from‐waste and recycling and/or composting in fairly equal measure. This infrastructural transformation, enacted over some 20 years, has been underpinned by the financialisation and marketisation of England’s municipal waste. Residual waste has been constituted as a financial asset whilst both residual waste and materials collected for recycling are the basis for further commodity production. The corporate landscape is dominated by large, European‐based transnationals. As well as documenting the regime and its emergence, the paper highlights, and accounts for, the multiple challenges it now faces – chiefly, the technical failure of residual waste solutions which necessitate a continued reliance on landfill for some councils, the collapse of the export markets on which England’s resource recovery has depended, and a radically changed policy landscape that seeks to move England towards a more circular economy. We suggest that local authorities’ waste infrastructure, procured in response to a linear economy, threatens and is threatened by these new policy directions.
City planning and floods: The strategy of Montpellier
Authors: Brun Alexandre , Volle Jean‐Paul
Published: March 2021

Located between Marseille and Barcelona, Montpellier is one of the most attractive cities of the Mediterranean coast. It has more than 460,000 inhabitants and grows by 7,500 more inhabitants every year. This is largely due to its positive image and its freshly constructed neighbourhoods “Antigone” and “Port‐Marianne.” From the late 1970s, the municipality’s strategy was to organise the urban sprawl to the east and then towards the sea in the south of the city. The Lez, a small coastal river, well known for its spectacular flash floods, was the spine of this new urban growth. Internationally renowned architects and planners have been recruited to build these new “green” neighbourhoods (in French “éco‐quartiers”) located on lands that used to be flooded regularly. This urban policy is largely due to the Montpellier’s former mayor Georges Frêche and his deputy, the geographer Raymond Dugrand. The “urban planning” concept, or “urban design” projects, have largely been used by the local experts and officials to describe this development, but seem to be misused in this case. It has being mostly a political city‐project, still having the same objective as more than 30 years ago: to turn Montpellier towards the seaside. This paper will return to the strategy used at that time and, in retrospect, all the interrogations that have followed in terms of sustainable development and flood risk management.
microRNA‐106b derived from endothelial cell–secreted extracellular vesicles prevents skin wound healing by inhibiting JMJD3 and RIPK3
Authors: Qi Lin , Lu Yufeng , Wang Zhaolin , Zhang Guiyun
Published: March 2021

Intriguingly, microRNAs (miRs) transferred as cargo in extracellular vesicles (EVs) can modulate wound healing through their regulation of fibroblast functions. In this study, we investigated the effects of miR‐106b transfer via EVs derived from human umbilical vein endothelial cells (HUVECs) on skin wound healing. Dual‐luciferase reporter gene assay identified that miR‐106b could target and inhibit JMJD3. RT‐qPCR analysis showed EVs isolated from HUVECs had enriched expression of miR‐106b. LL29 fibroblast cells and HaCaT keratinocytes were co‐cultured with HUVEC‐derived EVs, in which miR‐106b had been up‐regulated or down‐regulated by its mimic or inhibitor. The co‐culture with HUVEC‐derived EVs increased miR‐106b expression, and reduced the viability and adhesion of LL29 and HaCaT cells, whereas the inhibition of miR‐106b in HUVEC‐derived EVs enhanced the viability and adhesion of LL29 and HaCaT cells through up‐regulation of JMJD3. Next, we showed that JMJD3 overexpression enhanced LL29 and HaCaT cell viability and adhesion through elevating RIPK3, which induced the phosphorylation of AKT during the wound‐healing process. We next developed a mouse skin wound model to investigate the actions of miR‐106b in vivo after 14 days. The delivery of miR‐106b via HUVEC‐derived EVs delayed wound healing through suppression of collagen I content and angiogenesis, but had no effects on pro‐inflammatory cytokines. In conclusion, miR‐106b from HUVEC‐derived EVs inhibits JMJD3 and RIPK3, leading to the inhibition of skin wound healing, thus constituting a new therapeutic target.
Post‐menopausal oestrogen deficiency induces osteoblast apoptosis via regulating HOTAIR/miRNA‐138 signalling and suppressing TIMP1 expression
Authors: Xu Shao‐Yong , Shi Peng , Zhou Rui‐Ming
Published: March 2021

In this study, we aimed to explore the molecular mechanisms underlying the development of osteoporosis in post‐menopausal females. Real‐time PCR was conducted to measure the expression of potential lncRNAs involved in the osteoporosis of post‐menopausal females. In addition, Western blot and IHC assays were used to study the possible correlation among HOTAIR, miR‐138 and TIMP1, while a computational analysis was carried out to predict the ‘seed sequence’ responsible for the binding between miR‐138 and HOTAIR/TIMP1. Furthermore, luciferase reporter assays were conducted to validate the negative regulatory relationship between miR‐138 and TIMP1/HOTAIR. To evaluate the effect of oestrogen on the function of HOATIR and its downstream effectors, luciferase activity was measured in cells cotransfected with different vectors or treated with different doses of oestrogen. The results of the luciferase assay were further validated by real‐time PCR, Western blot, MTT assay and flow cytometry. Among the candidate lncRNAs, HOTAIR was the only lncRNA down‐regulated in post‐menopausal females. HOTAIR bound to miR‐138 and negatively regulated its expression. Meanwhile, miR‐138 could also bind to TIMP1 mRNA and reduce its expression. Furthermore, a dose‐dependent up‐regulation of HOTAIR was observed in cells treated with oestrogen, and the elevated HOTAIR increased the level of TIMP1 by targeting miR‐138. In addition, oestrogen promoted cell viability and suppressed cell apoptosis, and effects of oestrogen were blocked by the silencing of HOTAIR. Therefore, it can be concluded that oestrogen deficiency could induce the apoptosis of osteoblasts and lead to osteoporosis in post‐menopausal females via modulation of the HOTAIR/miR‐138/TIMP1 signalling axis.
CircPVT1 up‐regulation attenuates steroid‐induced osteonecrosis of the femoral head through regulating miR‐21‐5p‐mediated Smad7/TGFβ signalling pathway
Authors: Hao Yangquan , Lu Chao , Zhang Baogang , Xu Zhaochen , Guo Hao , Zhang Gaokui
Published: March 2021

Steroid‐induced osteonecrosis of the femoral head (SIONFH) has been a common disease following corticosteroid therapy. Presently, we aim to explore the functions of circular RNA (circ) PVT1 in SIONFH rats and the underlying mechanism. Glucocorticoid (GC) was used to treat SD rats and bone marrow‐derived mesenchymal stem cells (BMSCs) to construct SIONFH model in vitro and in vivo, respectively. The pathological injury of the femoral head in the SIONFH rats was detected via haematoxylin‐eosin (HE) staining and immunohistochemistry (IHC). The osteogenic differentiation, proliferation and apoptosis of BMSCs were detected. Western blot was used to detect Smad7, Bax, Bcl2 and Smad2/3. The potential targets of circPVT1 and miR‐21‐5p were validated through luciferase reporter gene assay and RNA pull‐down assay, respectively. We found that CircPVT1 was decreased in the femoral head of SIONFH rats and GC‐treated BMSCs, while miR‐21‐5p was markedly up‐regulated. Overexpressed circPVT1 attenuated the apoptosis and cell viability inhibition of BMSCs induced by GC, while miR‐21‐5p up‐regulation had the opposite effects. What's more, the in vivo experiments confirmed that up‐regulating circPVT1 repressed osteonecrosis in SIONFH rats through repressing apoptosis. Mechanistically, circPVT1 functioned as a ceRNA of miR‐21‐5p, which targeted at the 3'untranslated region of Smad7. CircPVT1 enhancing Smad7 and mitigating GC activated TGFβ/Smad2/3 pathway through inhibiting miR‐21‐5p. In conclusion, CircPVT1 exerts protective effects against SIONFH via modulating miR‐21‐5p‐mediated Smad7/TGFβ pathway.
Decentralized EU Policy Coordination in Crisis? The Case of Germany
Authors: Freudlsperger Christian , Weinrich Martin
Published: March 2021

Europeanization research found no general convergence towards centralized EU policy coordination, despite decentralized systems' comparatively slow and ineffective position‐taking. Does this finding hold against the threat, urgency, and uncertainty exerted by recent years' polycrisis? We posit that decentralized systems indeed persist, albeit in a three‐step reactive sequence in which situational centralization during crises dialectically reinforces decentralization in the long run. First, the prime minister's office harnesses a crisis to acquire hierarchical control of position‐taking. Second, to exploit the deep expertise of the bureaucracy and maximize its bargaining power on the EU‐level, it co‐opts a lead ministry. Third, due to the institutional underpinnings of the decentralized system, the lead ministry, rather than the prime minister's office, eventually retains the administrative capacities created in crisis. We illustrate this causal mechanism in a comparison of the German government's EU policy coordination during the Eurozone and Schengen crises.
Transport of oxytocin to the brain after peripheral administration by membrane‐bound or soluble forms of receptors for advanced glycation end‐products
Authors: Munesue Sei‐ichi , Liang MingKun , Harashima Ai , Zhong Jing , Furuhara Kazumi , Boitsova Elizabeta B , Cherepanov Stanislav M , Gerasimenko Maria , Yuhi Teruko , Yamamoto Yasuhiko , Higashida Haruhiro
Published: March 2021

Oxytocin (OT) is a neuropeptide hormone. Single and repetitive administration of OT increases social interaction and maternal behaviour in humans and mammals. Recently, it was found that the receptor for advanced glycation end‐products (RAGE) is an OT‐binding protein and plays a critical role in the uptake of OT to the brain after peripheral OT administration. Here, we address some unanswered questions on RAGE‐dependent OT transport. First, we found that, after intranasal OT administration, the OT concentration increased in the extracellular space of the medial prefrontal cortex (mPFC) of wild‐type male mice, as measured by push‐pull microperfusion. No increase of OT in the mPFC was observed in RAGE knockout male mice. Second, in a reconstituted in vitro blood‐brain barrier system, inclusion of the soluble form of RAGE (endogenous secretory RAGE [esRAGE]), an alternative splicing variant, in the luminal (blood) side had no effect on the transport of OT to the abluminal (brain) chamber. Third, OT concentrations in the cerebrospinal fluid after i.p. OT injection were slightly higher in male mice overexpressing esRAGE (esRAGE transgenic) compared to those in wild‐type male mice, although this did not reach statistical significance. Although more extensive confirmation is necessary because of the small number of experiments in the present study, the reported data support the hypothesis that RAGE may be involved in the transport of OT to the mPFC from the circulation. These results suggest that the soluble form of RAGE in the plasma does not function as a decoy in vitro.
SOX7 blocks vasculogenic mimicry in oral squamous cell carcinoma
Authors: Hong Kyoung‐Ok , Oh Kyu‐Young , Yoon Hye‐Jung , Swarup Neeti , Jung Minjung , Shin Ji‐Ae , Kim Jung‐Hwan , Chawla Kunal , Lee Jae‐Il , Cho Sung‐Dae , Hong Seong‐Doo
Published: March 2021

Background

Vasculogenic mimicry (VM) is the formation of an alternative circulatory system by aggressive tumor cells. The characteristics of VM and its underlying mechanism in oral squamous cell carcinoma (OSCC) remain unclear. This study aims to determine the relationship between VM in OSCC tissues and clinical outcomes and to investigate the biological role of SOX7 in VM in OSCC cells.

Methods

CD31/PAS staining was performed to evaluate VM in OSCC tissue. The relationships between VM and clinicopathological variables, and VM and SOX7 levels were analyzed. The correlation between SOX7 levels and cancer cohorts was investigated using in silico analysis. VM formation assay was performed to observe VM in vitro. To investigate the role of SOX7 in VM formation, SOX7 was transiently over‐expressed in SCC‐9 cells. VM‐modulating genes were identified by Western blotting.

Results

We found a positive correlation between VM and lymph node metastasis and patient survival in OSCC (p = 0.003). In silico analysis from The Cancer Genome Atlas and Gene Expression Omnibus database showed that down‐regulation of SOX7 expression was significantly correlated with OSCC patients (p = 0.0187) and lymph node metastasis (p = 0.0017). We also found that the presence of VM in OSCC tissue was inversely associated with SOX7 expression (p = 0.020). We observed that overexpression of SOX7 impaired VM formation by reducing the expression of VE‐cadherin, thereby inhibiting cell migration and invasion.

Conclusion

These results suggest that SOX7 plays an important role in the regulation of VM formation and may inhibit OSCC metastasis.
Phytochrome B and PHYTOCHROME INTERACTING FACTOR8 modulate seasonal growth in trees
Authors: Ding Jihua , Zhang Bo , Li Yue , André Domenique , Nilsson Ove
Published: March 2021

The seasonally synchronized annual growth cycle that is regulated mainly by photoperiod and temperature cues is a crucial adaptive strategy for perennial plants in boreal and temperate ecosystems.

Phytochrome B (phyB), as a light and thermal sensor, has been extensively studied in Arabidopsis. However, the specific mechanisms for how the phytochrome photoreceptors control the phenology in tree species remain poorly understood.

We characterized the functions of PHYB genes and their downstream PHYTOCHROME INTERACTING FACTOR (PIF) targets in the regulation of shade avoidance and seasonal growth in hybrid aspen trees. We show that while phyB1 and phyB2, as phyB in other plants, act as suppressors of shoot elongation during vegetative growth, they act as promoters of tree seasonal growth. Furthermore, while the Populus homologs of both PIF4 and PIF8 are involved in the shade avoidance syndrome (SAS), only PIF8 plays a major role as a suppressor of seasonal growth.

Our data suggest that the PHYB‐PIF8 regulon controls seasonal growth through the regulation of FT and CENL1 expression while a genome‐wide transcriptome analysis suggests how, in Populus trees, phyB coordinately regulates SAS responses and seasonal growth cessation.
Analgesic effects of indomethacin spray on drug‐induced oral mucositis pain in patients with cancer: A single‐arm cross‐sectional study
Authors: Hata Hironobu , Takada Shinya , Sato Jun , Yoshikawa Kazuhito , Imamachi Kenji , Edo Minako , Sagawa Tamotsu , Fujikawa Koshi , Ueda Michihiro , Matsuzaka Masashi , Kitagawa Yoshimasa
Published: March 2021

Aims

Symptomatic treatment is insufficient for chemotherapy‐ or targeted therapy‐induced oral mucositis (OM) pain, and benzydamine mouthwash is not commercially available in Japan. We evaluated the analgesic effects of an in‐hospital preparation of 0.25% indomethacin spray (IMS) on anticancer drug‐induced OM pain.

Methods

This single‐arm prospective trial enrolled 20 patients (median age 62.0 years) with OM and numerical rating scale scores of ≥5 who were undergoing chemotherapy or targeted therapy in our hospital. Pain scores were recorded using a visual analog scale (VAS) before and 30 min after IMS administration. Pain relief (PR) scores were recorded at 15, 30, and 60 min after IMS administration; total PR after 60 min (TOTPAR60) was calculated, and the mean PR score after 3 days (PR3days) was determined.

Results

The median (interquartile range) OM grade of the participants was 2.0 (2.0–2.3). The VAS score decreased significantly at 30 min after IMS administration (p = .001). The median (interquartile range) TOTPAR60 and PR3days were 6.0 (3.8–7.3) and 2.0 (2.0–3.0), respectively.

Conclusions

IMS helped improve patients’ quality of life. The risk of systemic adverse effects was low because of the low dose administered. IMS effectively relieved anticancer drug‐induced OM pain and may be useful for immediate self‐medication.
Assessments of stress of conscience, burnout and social support amongst care providers in home care and residential care for older people
Authors: Åhlin Johan , Ericson‐Lidman Eva , Strandberg Gunilla
Published: March 2021

Background

Studies points to that levels of stress of conscience and burnout among staff in healthcare contexts may seriously affect their health.

Aim

To compare assessments and associations of stress of conscience, perceptions of conscience, social support and burnout amongst care providers working in home care respectively residential care for older people.

Methods

This cross‐sectional descriptive comparative study was performed among all care providers working in home care (n = 227) and residential care of older people (n = 354) in a municipality in northern Sweden. Data was collected using four different questionnaires. Analysis were performed using partial least square regression, descriptive statistics, statistical tests and effect size measures.

Results

Care providers in residential care of older people assessed higher levels of stress of conscience compared to those working in home care. Exhaustion was an important predictor for belonging to the group of care providers working in residential care of older people. The most important predictor for belonging to the group of care providers working in home care were social support from one's immediate superior and co‐workers. Women assessed significantly higher levels of stress of conscience and exhaustion compared to men.

Conclusion

Further research seems needed to investigate what the high levels of stress of conscience is caused by. A combined intervention consisting of work‐directed measures against burnout and measures aiming at reducing stress of conscience is suggested.
“Maybe I’m just not good enough?”: British swimmers’ experiences of attempting to qualify for the Olympic Games
Authors: Mitchell Libby A. , Knight Camilla J. , Morris Robert , Mellalieu Stephen D.
Published: March 2021

The purpose of this study was to explore the transitional experiences of British swimmers as they attempted to qualify for the Olympic Games and gain a place in the British Swimming World Class Performance Programme. An interpretive phenomenological analysis (IPA) approach was adopted (Smith JA. Psychol Health 1996;11:261–271). Six swimmers (aged 20–25 years), one of each of their parents, and four coaches completed interviews leading up to and following Olympic trials over an eight‐month period. Audio recordings were transcribed verbatim and analyzed following the guidelines set out by Smith and Osborne (Smith JA, Osborn M. Qualitative psychology: A practical guide to research methods. London: Sage; 2003:51–80). Results indicated that athletes’ transition experiences were characterized by a range of demands, which were categorized into five higher‐order themes (a) Questioning “Am I good enough?”; (b) Managing and fulfilling expectations; (c) Operating within an environment that is working against them; (d) Lacking support and understanding of self and demands; and (e) Maintaining balance versus being an international swimmer. Overall, the results indicate that this attempted transition is complex, challenging, and unique and largely influenced by self‐confidence. Addressing the individual factors impacting on athletes’ self‐confidence appears critical to enhancing swimmers’ transitional experiences at the highest level.
Turgor regulation defect 1 proteins play a conserved role in pollen tube reproductive innovation of the angiosperms
Authors: Ke Chang‐Jiao , Lin Xian‐Ju , Zhang Bao‐Yu , Chen Li‐Yu
Published: March 2021

Sexual reproduction in angiosperms is siphonogamous, and the interaction between pollen tube and pistil is critical for successful fertilization. Our previous study demonstrated that mutation of the Arabidopsis turgor regulation defect 1 (TOD1) gene leads to reduced male fertility, a result of retarded pollen tube growth in the pistil. TOD1 encodes a Golgi‐localized alkaline ceramidase, a key enzyme for the production of sphingosine‐1‐phosphate (S1P), which is involved in the regulation of turgor pressure in plant cells. However, whether TOD1s play a conserved role in the innovation of siphonogamy is largely unknown. In this study, we provide evidence that OsTOD1, which is similar to AtTOD1, is also preferentially expressed in rice pollen grains and pollen tubes. OsTOD1 knockout results in reduced pollen tube growth potential in rice pistil. Both the OsTOD1 genomic sequence with its own promoter and the coding sequence under the AtTOD1 promoter can partially rescue the attod1 mutant phenotype. Furthermore, TOD1s from other angiosperm species can partially rescue the attod1 mutant phenotype, while TOD1s from gymnosperm species are not able to complement the attod1 mutant phenotype. Our data suggest that TOD1 acts conservatively in angiosperms, and this opens up an opportunity to dissect the role of sphingolipids in pollen tube growth in angiosperms.
Isolation of Arabidopsis extracellular ATP binding proteins by affinity proteomics and identification of PHOSPHOLIPASE C‐LIKE 1 as an extracellular protein essential for fumonisin B1 toxicity
Authors: Smith Sarah J. , Goodman Heather , Kroon Johan T. M. , Brown Adrian P. , Simon William J. , Chivasa Stephen
Published: March 2021

ATP is secreted to the extracellular matrix, where it activates plasma membrane receptors for controlling plant growth and stress‐adaptive processes. DOES NOT RESPOND TO NUCLEOTIDES 1 (DORN1), was the first plant ATP receptor to be identified but key downstream proteins remain sought after. Here, we identified 120 proteins secreted by Arabidopsis cell cultures and screened them for putative stress‐responsive proteins using ATP‐affinity purification. We report three Arabidopsis proteins isolated by ATP‐affinity: PEROXIDASE 52, SUBTILASE‐LIKE SERINE PROTEASE 1.7 and PHOSPHOLIPASE C‐LIKE 1. In wild‐type Arabidopsis, the expression of genes encoding all three proteins responded to fumonisin B1, a cell death‐activating mycotoxin. The expression of PEROXIDASE 52 and PHOSPHOLIPASE C‐LIKE 1 was altered in fumonisin B1‐resistant salicylic acid induction‐deficient (sid2) mutants. Exposure to fumonisin B1 suppressed PHOSPHOLIPASE C‐LIKE 1 expression in sid2 mutants, suggesting that the inactivation of this gene might provide mycotoxin tolerance. Accordingly, gene knockout mutants of PHOSPHOLIPASE C‐LIKE 1 were resistant to fumonisin B1‐induced death. The activation of PHOSPHOLIPASE C‐LIKE 1 gene expression by exogenous ATP was not blocked in dorn1 loss‐of‐function mutants, indicating that DORN1 is not required. Furthermore, exogenous ATP rescued both the wild type and the dorn1 mutants from fumonisin‐B1 toxicity, suggesting that different ATP receptor(s) are operational in this process. Our results point to the existence of additional plant ATP receptor(s) and provide crucial downstream targets for use in designing screens to identify these receptors. Finally, PHOSPHOLIPASE C‐LIKE 1 serves as a convergence point for fumonisin B1 and extracellular ATP signalling, and functions in the Arabidopsis stress response to fumonisin B1.
Advanced oxidation as tertiary treatment for recovery of effluent from an integrated algal pond system
Authors: Jimoh Taobat A. , Laubscher Richard K. , Askew Derek J. , Cowan A. Keith
Published: March 2021

In contemporary water‐scarce regions and with increasing pressure on the built environment, access to quality water within the peri‐urban space is of concern. It has been argued that integrated algal pond systems (IAPS) are ideally suited as these systems offer value recovery and water for irrigation. Advanced oxidation (AO) was evaluated as tertiary treatment for inclusion into the IAPS process. Chemical oxygen demand (COD), total suspended solids (TSS) and ammonium‐N in effluent from an IAPS treating municipal sewage were monitored after exposure to AO. All measured parameters were reduced but reduction in COD occurred only after long‐term exposure or high dosage. COD, TSS and ammonium‐N concentrations were reduced by 2%, 30% and 28%, respectively, within 24 h. Addition of an AO unit to the IAPS process can upgrade water quality to a level satisfactory for recovery to irrigation or for discharge without any substantial increase in process footprint.