bluuebunny/crossref_metadata_2025 huggingface dataset:
Powerful authentication regime applicable to naval OFP integrated development (PARANOID): a vision for non-circumventable code signing and traceability for embedded avionics software
Authors: Garcia Joe , Shannon Russell , Jacobson Aaron , Mosca William , Burger Michael , Maldonado Roberto
Published: June 2021

Purpose

This paper aims to describe an effort to provide for a robust and secure software development paradigm intended to support DevSecOps in a naval aviation enterprise (NAE) software support activity (SSA), with said paradigm supporting strong traceability and provability concerning the SSA’s output product, known as an operational flight program (OFP). Through a secure development environment (SDE), each critical software development function performed on said OFP during its development has a corresponding record represented on a blockchain.

Design/methodology/approach

An SDE is implemented as a virtual machine or container incorporating software development tools that are modified to support blockchain transactions. Each critical software development function, e.g. editing, compiling, linking, generates a blockchain transaction message with associated information embedded in the output of a said function that, together, can be used to prove integrity and support traceability. An attestation process is used to provide proof that the toolchain containing SDE is not subject to unauthorized modification at the time said critical function is performed.

Findings

Blockchain methods are shown to be a viable approach for supporting exhaustive traceability and strong provability of development system integrity for mission-critical software produced by an NAE SSA for NAE embedded systems software.

Practical implications

A blockchain-based authentication approach that could be implemented at the OFP point-of-load would provide for fine-grain authentication of all OFP software components, with each component or module having its own proof-of-integrity (including the integrity of the used development tools) over its entire development history.

Originality/value

Many SSAs have established control procedures for development such as check-out/check-in. This does not prove the SSA output software is secure. For one thing, a build system does not necessarily enforce procedures in a way that is determinable from the output. Furthermore, the SSA toolchain itself could be attacked. The approach described in this paper enforces security policy and embeds information into the output of every development function that can be cross-referenced to blockchain transaction records for provability and traceability that only trusted tools, free from unauthorized modifications, are used in software development. A key original concept of this approach is that it treats assigned developer time as a transferable digital currency.
Crypto assets regulation in the UK: an assessment of the regulatory effectiveness and consistency
Authors: Huang Sherena Sheng
Published: June 2021

Purpose

The UK authority published its first regulatory guidance on crypto-assets in July 2019. This paper aims to critically evaluate the effectiveness of the crypto-asset regulation in the UK and the consistency of the existing regulatory scheme.

Design/methodology/approach

This paper adopts comparative methods to carry out the analysis. The paper begins by elaborating the development of crypto-assets alongside the financial innovation in the world and pinpointing the core Acts and Regulations applied to crypto-assets in the UK. The paper also discusses a court case in the EU to highlight an argument among legal professions concerning crypto-assets classification.

Findings

Through carefully analysing relevant primary and secondary legislation of the UK and EU, this paper identifies some unclarified issues in the regulatory framework and discovers three flaws in the regulatory system. The paper concludes that the effectiveness of the current regulatory scheme is poor and room for improvement exists.

Originality/value

The paper provides the first review and a thorough analysis of the Laws and Acts applied to the crypto-asset regulation in the UK. It also calls on a simpler and clearer regulatory scheme from the perspectives of market participants and consumers. The discovered issues in the crypto-asset regulation in the UK may urge authorities to improve the existing regulatory frameworks and legal provisions.
Mental health: working from home and the use of technology
Authors: Newey Mark
Published: June 2021

Purpose

The purpose of this paper is to discuss why mental health education in the workplace is vital. The paper aims to give HR managers and directors an understanding of mental health education and advice on how to imbed a culture of mental health well-being into the workplace.

Design/methodology/approach

The feature identifies the issues faced in the UK’s workplace with mental health issues, such as stress, anxiety and depression. The research identifies much desktop research, as well as authors 20+ plus years’ experience of work, in the field as a qualified psychotherapist. The paper also addresses latest research that suggests employees are happier to turn to technology rather than human contact to address their mental health concerns. The feature was drafted during the Covid-19 pandemic when mental health issues were recorded at an all-time high.

Findings

Mental Health has become a major issue within the workplace, and much work has taken place to rid stigma of mental health issues. It is essential that industry embed mental health education into their organisations to create healthy futures for all. Employees want their organisations to offer support, preferably in an online, always available, service.

Originality/value

Although there’s much discussion and awareness of mental health issues, mental health education is rarely understood.
Conclusion - building resilient destinations and communities: the need for greater industry, community and academic collaboration
Authors: Miller DeMond Shondell
Published: June 2021

Purpose

This paper provides a conclusion to the theme issue by commenting on the contributions made by the writing team. Moreover, this paper advocates the use of interdisciplinary teams to build resilience in the tourism and hospitality industries.

Design/methodology/approach

This paper draws on research and best practices cited in the preceding papers and offers viewpoints that link theory and practice.

Findings

Although there is no one specific way to summarize the contents of this theme issue, the findings build on the idea of forging trust and alliances to advance local and global resilience.

Originality/value

Post-disaster resilience is certainly relevant to the tourism and hospitality industries amid the ongoing COVID-19 pandemic. Findings and implications from this series of articles, interviews, and viewpoints can be used to aid the recovery of the tourism and hospitality industries.
Bridging behavioural factors and standard bio‐economic modelling in an agent‐based modelling framework
Authors: Huber Robert , Xiong Hang , Keller Kevin , Finger Robert
Published: June 2021

Agent‐based models are important tools for simulating farmers’ behaviour in response to changing environmental, economic or institutional conditions and policies. This article introduces an agent‐based modelling approach that combines behavioural factors with standard bio‐economic modelling of agricultural production. More specifically, our framework integrates the cumulative prospect theory and social interactions with constrained optimisation decisions in agricultural production. We apply our modelling approach to an exemplary bio‐economic model on the assessment of weed control decisions. Results show the effects of heterogeneous farm decision‐making and social networks on mechanical weed control and herbicide use. This framework provides a generic and conceptually sound approach to improve the scope for representing farmers’ decision‐making and allows the simulation of their decisions and recent advances in behavioural economics to be aligned with existing bio‐economic models of agricultural systems.
Downregulation of miR‐98‐5p expression induces interleukin‐6 expression in rheumatoid fibroblast‐like synoviocytes
Authors: Wang Shujun , Geng Qin , Zhang Hongju , Du Qing , Wei Qiaofeng , Cui Yanhui , Zhang Xiuying , Yuan Min
Published: June 2021

Aim

The increased level of interleukin‐6 (IL‐6) plays a significant role in the pathogenesis of rheumatoid arthritis (RA). Specific blockade of IL‐6 or its receptor has been used successfully in treating RA. MicroRNAs can regulate gene expression and act as regulators of target genes. Manipulation of specific microRNAs provides a novel therapeutic strategy for treating/preventing diseases. This study explored the role of miR‐98‐5p in the regulation of IL‐6 expression in rheumatoid fibroblast‐like synoviocytes (RA‐FLSs).

Methods

Real‐time PCR was used to detect miR‐98‐5p expression in RA‐FLSs and normal human fibroblast‐like synovial cells (HFLSs). Site‐directed gene mutagenesis and reporter gene assay were performed to identify the interaction between miR‐98‐5p and IL‐6. Manipulation of miR‐98‐5p expression in RA‐FLS used transfection with miR‐98‐5p mimic or inhibitor. Stimulation of FLSs with IL‐1β induced IL‐6 production. Enzyme‐linked immunosorbent assay was used to detect the level of IL‐6 secreted into the RA‐FLS culture supernatant.

Results

Compared with HFLSs, the expression of miR‐98‐5p in RA‐FLSs was significantly downregulated, and was negatively correlated with DAS28 scores and rheumatoid factor. In patients with anti‐keratin antibody‐positive RA, the expression level of miR‐98‐5p was lower. miR‐98‐5p negatively regulated the expression of IL‐6 in RA‐FLSs. After IL‐1β stimulation, the expression of miR‐98‐5p decreased and the level of IL‐6 protein was upregulated during IL‐6 secretion.

Conclusion

These data suggest that manipulation of miR‐98‐5p, which negatively modulates IL‐6 expression, may be a potential clinical approach in RA.
An artificial nervous system to treat chronic stroke
Authors: Serruya Mijail D. , Rosenwasser Robert H.
Published: June 2021

Despite remarkable advances in the treatment of numerous medical conditions, neurological disease and injury remains an outstanding challenge and cause of disability worldwide. The decreased regenerative capacity and extreme complexity and heterogeneity of nervous tissue, in particular the brain, and the fact that the brain remains the least understood organ, have hampered our ability to provide definitive treatments for prevalent conditions such as stroke. Stroke is the second‐leading cause of death worldwide, and the nervous system is intimately involved in other prevalent conditions including ischemic heart disease, diabetes mellitus, and hypertension. Advances in neuromodulation, electroceuticals, microsurgical techniques, optogenetics, brain–computer interfaces, and autologous constructs offer potential solutions to address the otherwise permanent neurological deficits of stroke and other conditions. Here we review these various approaches to build an “artificial nervous system” that could restore function and independence in people living with these conditions. We focus on stroke both because it is the leading cause of neurological disability worldwide and because we anticipate that advances in the reversal of stroke‐related deficits will have ripple effects benefiting people with other neurological conditions including spinal cord injury, traumatic brain injury, ALS, and muscular dystrophy.
Counteracting subliminal cues that threaten national identity
Authors: van Breen Jolien A. , de Lemus Soledad , Spears Russell , Kuppens Toon
Published: June 2021

In spite of their subtle nature, subliminal cues of group devaluation can have profound effects on members of targeted groups. Across three studies, we examine factors that allow people to counteract subliminal cues of group devaluation. We do this in the context of Spanish–German intergroup relations following the 2008 financial crisis. Throughout the crisis, narratives in politics and the media have drawn on national stereotypes to legitimize the economic situation in Spain. We argue that this represents a threat to our Spanish participants and that exposure to subliminal cues that reflect this threat will trigger responses that counteract this threat. Indeed, results showed that when subliminal associations legitimize the disadvantage faced by the group, our Spanish participants reversed the subliminal associations to which they were exposed. These findings show that Spanish participants are able to counteract the devaluation of their national in‐group, even when that devaluation occurs outside of conscious awareness.
AIM2 deletion enhances blood‐brain barrier integrity in experimental ischemic stroke
Authors: Xu Si‐yi , Bian Hui‐jie , Shu Shu , Xia Sheng‐nan , Gu Yue , Zhang Mei‐juan , Xu Yun , Cao Xiang
Published: June 2021

Aims

Ischemic stroke is a life‐threatening disease with limited therapeutic strategies. Blood‐brain barrier (BBB) disruption is a critical pathological process that contributes to poor outcomes in ischemic stroke. We previously showed that the microglial inhibition of the inflammasome sensor absent in melanoma 2 (AIM2) suppressed the inflammatory response and protected against ischemic stroke. However, whether AIM2 is involved in BBB disruption during cerebral ischemia is unknown.

Methods

Middle cerebral artery occlusion (MCAO) and oxygen‐glucose deprivation/reoxygenation (OGD/R) were used to mimic cerebral ischemia in mice and brain microvascular endothelial cells (HBMECs), respectively. The infarct volume, neurological deficits, and BBB permeability were measured in mice after MCAO. Transendothelial electrical resistance (TEER) and neutrophil adhesion to the HBMEC monolayer were assessed after OGD/R treatment. Western blot and immunofluorescence analyses were conducted to evaluate the expression of related proteins.

Results

AIM2 was shown to be expressed in brain endothelial cells and upregulated after ischemic stroke in the mouse brain. AIM2 deletion reduced the infarct volume, improved neurological and motor functions, and decreased BBB disruption. In vitro, OGD/R significantly increased the protein levels of AIM2 and ICAM‐1 and decreased those of the tight junction (TJ) proteins ZO‐1 and occludin. AIM2 knockdown effectively protected BBB integrity by promoting the expression of TJ proteins and decreasing ICAM‐1 expression and neutrophil adhesion. Mechanistically, AIM2 knockdown reversed the OGD/R‐induced increases in ICAM‐1 expression and STAT3 phosphorylation in brain endothelial cells. Furthermore, treatment with the p‐STAT3 inhibitor AG490 mitigated the effect of AIM2 on BBB breakdown.

Conclusion

Our findings indicated that inhibiting AIM2 preserved the BBB integrity after ischemic stroke, at least partially by modulating STAT3 activation and that AIM2 may be a promising therapeutic target for cerebral ischemic stroke.
Diagnostic accuracy of point of care faecal immunochemical testing using a portable high‐speed quantitative analyser for diagnosis in 2‐week wait patients
Authors: Maclean William , Mackenzie Paul , Limb Chris , Zahoor Zahida , Whyte Martin B. , Rockall Timothy , Benton Sally C. , Jourdan Iain
Published: June 2021

Aim

Laboratory‐based faecal immunochemical testing (FIT) is the gold standard for detecting the presence of blood in the stool. The aim was to perform a diagnostic accuracy study to confirm if a point of care (POC) analyser for FIT could be safely used as an adjunct in the triage and management of 2‐week wait (TWW) colorectal patients.

Methods

The Point of Care Faecal Immunochemical Testing (POC FIT) prospective observational cohort study was designed for TWW patients at a regional referral centre. Between July 2019 and March 2020, patients were invited to perform and bring a FIT sample to clinic. FIT was completed within the clinic appointment using a POC quantitative analyser that has a 2‐min processing time (QuikRead go®). Patients and clinicians were blinded to results within the clinic appointment. The results were compared with subsequent diagnostic outcomes. Faecal haemoglobin of <10 µg haemoglobin/g of faeces was considered a negative result. Sensitivities for colorectal cancer (CRC) and combined serious bowel disease (SBD) were calculated using this pre‐determined cut‐off.

Results

A total of 553 patients were included for analytical comparison with diagnostic outcomes. There were 14 (2.5%) patients with CRC and 52 (9.4%) with SBD. The sensitivities for CRC and SBD were 92.9% (95% CI 68.5%–98.7%) and 76.9% (95% CI 63.9%–86.3%) respectively. 379 (68.5%) patients had a negative FIT result (negative predictive value for CRC was 99.7%).

Conclusions

This POC FIT device is a useful adjunct to better manage TWW patients. The high observed sensitivity for CRC offers opportunities, within a single consultation, for improved triage and rationalization of investigation for those with bowel symptoms.
Lipid droplet screen in human hepatocytes identifies TRRAP as a regulator of cellular triglyceride metabolism
Authors: Abbey Deepti , Conlon Donna , Rainville Christopher , Elwyn Susannah , Quiroz‐Figueroa Katherine , Billheimer Jeffrey , Schultz David C. , Hand Nicholas J. , Cherry Sara , Rader Daniel J.
Published: June 2021

Hepatocytes store triglycerides (TGs) in the form of lipid droplets (LDs), which are increased in hepatosteatosis. The regulation of hepatic LDs is poorly understood and new therapies to reduce hepatosteatosis are needed. We performed a siRNA kinase and phosphatase screen in HuH‐7 cells using high‐content automated imaging of LDs. Changes in accumulated lipids were quantified with developed pipeline that measures intensity, area, and number of LDs. Selected “hits,” which reduced lipid accumulation, were further validated with other lipid and expression assays. Among several siRNAs that resulted in significantly reduced LDs, one was targeted to the nuclear adapter protein, transformation/transcription domain‐associated protein (TRRAP). Knockdown of TRRAP reduced triglyceride accumulation in HuH‐7 hepatocytes, in part by reducing C/EBPα‐mediated de novo synthesis of TGs. These findings implicate TRRAP as a novel regulator of hepatic TG metabolism and nominate it as a potential drug target for hepatosteatosis.
The influence of habitat association on swimming performance in marine teleost fish larvae
Authors: Downie Adam T. , Leis Jeffrey M. , Cowman Peter F. , McCormick Mark I. , Rummer Jodie L.
Published: June 2021

Latitude and body size are generally considered key drivers of swimming performance for larval marine fishes, but evidence suggests that evolutionary relationships and habitat may also be important. We used a comparative phylogenetic framework, data synthesis and case study approach to investigate how swimming performance differs among larvae of fish species across latitude. First, we investigated how swimming performance changed with body length, and we found that temperate reef fishes have the greatest increases in swimming performance with length. Secondly, we compared differences in three swimming performance metrics (critical swimming speed, in situ swimming, and endurance) among post‐flexion larvae, whilst considering phylogenetic relationships and morphology, and we found that reef fishes have higher swimming capacity than non‐reef (pelagic and non‐reef demersal) fishes, which is likely due to larger, more robust body sizes. Thirdly, we compared swimming performance of late‐stage larvae of tropical fishes with oceanographic data to better understand the ecological relevance of their high‐capacity swimming. We found that reef fishes have high swimming performance and grow larger than non‐reef fish larvae, which we suggest is due to the pressures to find a specific, patchily distributed habitat upon which to settle. Given the current bias towards studies on percomorph fishes at low latitudes, we highlight that there is a need for more research on temperate reef fish larvae and other percomorph lineages from high latitudes. Overall, our findings provide valuable context to understand how swimming and morphological traits that are important for dispersal and recruitment processes are selected for among teleost fish larvae.
If We Measure It, They Will Come: A Realist Evaluation Approach in a Therapeutic Jurisprudence Context
Authors: Petrucci Carrie J.
Published: June 2021

Realist evaluation asks what works best for whom under what circumstances and why. Therapeutic jurisprudence seeks to explore how the therapeutic design and application of the law can support therapeutic and anti‐therapeutic outcomes. This article presents a proposed evaluation framework utilizing realist evaluation in a therapeutic jurisprudence context for family court interventions. Three key topics that make up the framework are described: mediation and moderation to document what works best for whom under what circumstances, analytical strategies to achieve good enough measurement of relevant constructs in the theory, and context‐mechanism‐outcome pattern hypotheses and generative causation used in realist evaluation.
Aged soils contribute little to contemporary carbon cycling downstream of thawing permafrost peatlands
Authors: Tanentzap Andrew J. , Burd Katheryn , Kuhn McKenzie , Estop‐Aragonés Cristian , Tank Suzanne E. , Olefeldt David
Published: June 2021

Vast stores of millennial‐aged soil carbon (MSC) in permafrost peatlands risk leaching into the contemporary carbon cycle after thaw caused by climate warming or increased wildfire activity. Here we tracked the export and downstream fate of MSC from two peatland‐dominated catchments in subarctic Canada, one of which was recently affected by wildfire. We tested whether thermokarst bog expansion and deepening of seasonally thawed soils due to wildfire increased the contributions of MSC to downstream waters. Despite being available for lateral transport, MSC accounted for ≤6% of dissolved organic carbon (DOC) pools at catchment outlets. Assimilation of MSC into the aquatic food web could not explain its absence at the outlets. Using δ13C‐Δ14C‐δ15N‐δ2H measurements, we estimated only 7% of consumer biomass came from MSC by direct assimilation and algal recycling of heterotrophic respiration. Recent wildfire that caused seasonally thawed soils to reach twice as deep in one catchment did not change these results. In contrast to many other Arctic ecosystems undergoing climate warming, we suggest waterlogged peatlands will protect against downstream delivery and transformation of MSC after climate‐ and wildfire‐induced permafrost thaw.
Spatiotemporal Multi‐objective Optimization for Competitive Mobile Vendors’ Location and Routing Using De Facto Population Demands
Authors: Cho Seonga , Lee Gunhak
Published: June 2021

Mobile vendors such as food trucks have become viable players in the food service market as a relatively new business model based on high mobility and flexibility. To remain competitive against typical brick and mortar establishments, it is important for mobile food vendors to operate at sites that will generate sufficient revenue, which may mean navigating to locations of high demand and low competition. This study addresses the optimal locations and routing of mobile vendors along different objectives that could contribute to higher revenue. We develop a multi‐objective spatiotemporal optimization of food trucks by explicitly considering the dynamics of urban population distribution and thus potential customer demand. For an empirical application, we focus on the location and routing problems of food trucks in Seoul, Korea. The results show that several noninferior solution sets are possible for simultaneously maximizing demand capture while reducing market competition. A routing between optimal locations for food trucks is also suggested. This research could provide useful insights and practical solutions that are directly applicable to various mobile vendors.
Spontaneous spinal epidural hemorrhage and sentinel headache—A case report
Authors: Hanna Joseph P. , Absher John R. , Enyart David S.
Published: June 2021

Objectives/Background

Expand the differential diagnosis of sentinel headache to include spontaneous spinal epidural hematoma (SSEH) and reinforce the need for lumbar puncture in the evaluation of thunderclap headache. SSEH is a rare clinical presentation especially in the absence of bleeding tendencies. Clinicians recognize SSEH with typical presenting signs and symptoms including regional paraspinal muscular contraction and pain along with myelopathy. Although thunderclap headache usually does not connote vascular rupture in the spinal epidural compartment, SSEH may rarely present with sentinel headache and later evolve into a myelopathy.

Results and Conclusion

Sentinel headache may be the sole symptom following spontaneous spinal epidural hemorrhage preceding both myelopathic and meningeal signs and symptoms. SSEH can best be diagnosed by lumbar puncture at this early moment potentially averting spinal cord injury.
A Community Jury on initiating weight management conversations in primary care
Authors: Beeken Rebecca J. , Scott Anna M. , Sims Rebecca , Cleo Gina , Clifford Helen , Glasziou Paul , Thomas Rae
Published: June 2021

Background

Current guidelines recommend that patients attending general practice should be screened for excess weight, and provided with weight management advice.

Objective

This study sought to elicit the views of people with overweight and obesity about the role of GPs in initiating conversations about weight management.

Methods

Participants with a body mass index ≥25 were recruited from a region in Australia to take part in a Community Jury. Over 2 days, participants (n = 11) deliberated on two interconnected questions: ‘Should GPs initiate discussions about weight management?’ And ‘if so, when: (a) opportunistically, (b) in the context of disease prevention, (c) in the context of disease management or (d) other?’ The jury deliberations were analysed qualitatively to elicit their views and recommendations.

Results

The jury concluded GPs should be discussing weight management, but within the broader context of general health. The jury were divided about the utility of screening. Jurors felt GPs should initiate the conversation if directly relevant for disease prevention or management, otherwise GPs should provide opportunities for patients to consent to the issue being raised.

Conclusion

The jury's verdict suggests informed people affected by overweight and obesity believe GPs should discuss weight management with their patients. GPs should feel reassured that discussions are likely to be welcomed by patients, particularly if embedded within a more holistic focus on person‐centred care.

Public contribution

Members of the public took part in the conduct of this study as jurors, but were not involved in the design, analysis or write‐up.
The synthesis of biotemplate‐based Bi2WO6/TiO2 composite photocatalyst for degradation of microcystin
Authors: Lin Yingzi , Ji Li , Zhang Dongyan , Zhu Yang , Li Yang , Chen Junjie , Zou Deqiang
Published: June 2021

Microcystin is a harmful hepatic toxin produced by cyanobacteria, is a serious threat due to its toxicity to water ecosystems, and it is found recently that TiO2 photocatalyst is effective in degradation of microcystin. In this study, hierarchical porous Bi2WO6/ TiO2 composite photocatalysts were synthesized with a novel hydrothermal method by using rice husk as the biological template. The results showed that the original micro‐ and nanopores of rice husk were efficiently replicated by the synthesized porous TiO2 photocatalyst with a specific surface area of 137.09 m2/g, which increased by nearly 100 m2/g over the surface area. SEM, TEM, XRD, and XPS spectra showed that heterogeneous structures were formed by Bi2WO6 and TiO2, with which process the crystal structures of both were not affected. In the meantime, we studied the effect of hierarchical porous TiO2 photo‐catalyst, pure TiO2 photo‐catalyst, Bi2WO6 photo‐catalyst, Bi2WO6/ hierarchical porous TiO2 photo‐catalyst on degradation of 1 mg/L MC‐LR, and the results showed that to use the unique silicon‐carbon structure of rice husk to prepare hierarchical porous TiO2 photo‐catalyst can have the degradation rate of 53.5%, which is higher than that of commercially available TiO2 photo‐catalyst by 13.8%. Compared with a single photo‐catalyst, the photo‐catalytic activity of Bi2WO6/ hierarchical porous TiO2 photo‐catalyst is significantly improved. The optimal mingling amount of Bi2WO6 is 0.2 mol/mol. At this time, the degradation rate of MC‐LR is 85.3%, and the main active substances for degradation are h+ and ·OH. In addition, the degradation process of MC‐LR fit well with the kinetic model of Quasi Primary Reaction. The insight of green synthesis of Bi2WO6/ TiO2 composite photocatalysts for degradation of microcystins was provided by this study.
Procyanidin B2 alleviates liver injury caused by cold stimulation through Sonic hedgehog signalling and autophagy
Authors: Ma Li , Li Chengxu , Lian Shuai , Xu Bin , Lv Hongming , Liu Yanzhi , Lu Jingjing , Ji Hong , Li Shize , Guo Jingru , Yang Huanmin
Published: June 2021

Procyanidin B2 (PB2), a naturally occurring flavonoid abundant in a wide range of fruits, has been shown to exert antioxidant, anti‐inflammatory and anticancer properties. However, the role of PB2 in the prevention of cold stimulation (CS)‐induced liver injury. The present study was undertaken to determine the effects of PB2 on liver injury induced by cold stimulation and its potential molecular mechanisms. The present study results showed that treatment with PB2 significantly reduced CS‐induced liver injury by alleviating histopathological changes and serum levels of alanine transaminase and aspartate transaminase. Moreover, treatment with PB2 inhibited secretion of inflammatory cytokines and oxidative stress in cold‐stimulated mice. PB2 reduced cold stimulation‐induced inflammation by inhibiting TLR4/NF‐κB and Txnip/NLRP3 signalling. Treatment with PB2 reduced oxidative stress by activating Nrf‐2/Keap1, AMPK/GSK3β signalling pathways and autophagy. Furthermore, simultaneous application of Shh pathway inhibitor cyclopamine proved that PB2 targets the Hh pathway. More importantly, co‐treatment with PB2 and cyclopamine showed better efficacy than monotherapy. In conclusion, our findings provide new evidence that PB2 has protective potential against CS‐induced liver injury, which might be closely linked to the inhibition of Shh signalling pathway.
Decreased Annexin A1 expression enhances sensitivity to docetaxel, cisplatin and 5‐fluorouracil combination induction chemotherapy in oral squamous cell carcinoma
Authors: Sun Wenwen , Zhao Tongchao , Aladelusi Timothy O. , Ju Wutong , Zhang Zhiyuan , Zhong Laiping , Zhu Dongwang
Published: June 2021

Background

Annexin A1, a member of the Annexin superfamily, has been shown to play a vital role in a broad range of molecular and cellular processes. This study aims to explore the relationship between the Annexin A1 expression and the clinical response to cisplatin, docetaxel and 5‐fluorouracil (TPF) as induction chemotherapy in patients with oral squamous cell carcinoma (OSCC).

Methods

This study recruited two hundred thirty‐two patients from a III/IVA OSCC trial. Immunohistochemistry was used to assess the level of Annexin A1 expression. Overexpression and knockdown methods in HB96, HN4 and CAL27 cell lines were used to assess the role of Annexin A1 in the neoplastic cellular response to chemotherapy.

Results

We found that reduced expression of Annexin A1 conferred a prognostic benefit from induction chemotherapy based on the TPF drug combination in patients with moderately/poorly differentiated disease. Using an in vitro model, we found that low Annexin A1 enhanced cellular proliferation by activating the EGFR/AKT signalling pathway and inhibiting p27 expression. Furthermore, low Annexin A1 initiated a significant decrease in cell viability after treatment with TPF agents. In addition, downregulation of Annexin A1 promoted apoptosis induced by docetaxel, cisplatin and 5‐fluorouracil, and upregulation of Annexin A1 inhibited apoptosis.

Conclusion

Annexin A1 may be of prognostic value in patients with locally advanced OSCC who are managed with TPF chemotherapy, as low Annexin A1 promotes chemosensitivity to TPF chemotherapy in oral cancer cells via enhanced caspase‐dependent apoptosis.
The long way back: Development of Central European mountain forests towards old‐growth conditions after cessation of management
Authors: Albrich Katharina , Thom Dominik , Rammer Werner , Seidl Rupert
Published: June 2021

Questions

Primary forests fulfil important roles in preserving biodiversity, storing carbon and increasing ecological understanding. Yet, they have become very rare in Europe. An important policy goal is thus to increase the share of naturally developing forests by creating protected areas in formerly managed forests. Here, we investigated: (a) if and how such forests return to conditions similar to old‐growth; and (b) whether recently observed stand‐replacing natural disturbances in combination with climate change set them onto an alternative developmental pathway.

Location

Dürrenstein Wilderness Area (IUCN Cat. Ib) in the Austrian Alps, containing the Rothwald, one of the last primary forest remnants of Central Europe.

Methods

We built a chronosequence of 87 plots, spanning 220 years of forest development after the cessation of management, and compared them to old‐growth forests. We analysed the recovery of nine attributes of forest composition, structure and functioning. To evaluate stand‐level development of these attributes after recent natural disturbance and climate change, we additionally used a process‐based simulation model.

Results

Old‐growth forests showed a wide range of variability across investigated attributes. Forests converged to old‐growth conditions after management ceased, with seven out of the nine attributes falling within the range of old‐growth at the end of our chronosequence. The variation in tree diameters and the downed amount of deadwood were, however, still significantly lower than in old‐growth forests after 220 years of unmanaged stand development. Simulations did not indicate an alternative developmental pathway of recently disturbed stands.

Conclusions

While a full return to old‐growth conditions can take centuries, a number of important forest attributes recover quickly, indicating that protecting formerly managed forests is a valuable strategy to enrich forest landscapes. Our results indicate that the mountain forests of Central Europe have high ecological resilience, developing towards old‐growth conditions after both past management and current natural disturbance.
Is elimination of hepatitis C virus realistic by 2030: Eastern Europe
Authors: Isakov Vasily , Tsyrkunov Vladimir , Nikityuk Dmitry
Published: June 2021

The WHO elimination goals (diagnosis of 90% of the cases of hepatitis C virus (HCV), treatment coverage in 80% and a 65% reduction in deaths from HCV) are set to be reached by 2030. Although these elimination programmes are extremely important in the Eastern European countries (Russia, Ukraine, Belarus and Moldova) with a high prevalence of HCV, limited economic resources prevent their development and implementation. Regardless of the decrease in the incidence HCV in all Eastern European countries, low diagnosis and treatment access, especially in high‐risk populations, will not allow to achieve HCV elimination or even to control the infection by 2030.
Simultaneous optimization of 3D alignments and station locations for dedicated high‐speed railways
Authors: Song Taoran , Pu Hao , Schonfeld Paul , Zhang Hong , Li Wei , Hu Jianping
Published: June 2021

Determinations of alignments and station locations are major tasks in railway design, which jointly and fundamentally influence the construction and operation of the whole project. Currently, although considerable efforts have been invested into the separate optimization of alignments or station locations, the complex interactions between alignments and stations, as well as their concurrent impacts on railways still need further investigations. Therefore, this study focuses on modeling and optimization of passenger railway alignments and station locations simultaneously. A novel optimization model is formulated for maximizing net present value (NPV) considering comprehensive costs and revenue from riders over the railway's design life. Specifically, the comprehensive cost includes construction and operation costs of alignments and stations. The railway ridership is quantified by combining travel time and trip coverage using a logit function. Then, the railway revenue is estimated and combined with costs through an economic growth model to obtain the NPV. To solve this model, two customized and mutually exclusive methods, that is, the station‐alignment‐integration (SAI) and alignment‐station‐integration (ASI) methods, are developed based on a particle swarm algorithm. The SAI primarily searches for possible stations in the landscape and then generates alignments to connect adjacent stations. The ASI directly yields the main alignment, on which potential stations are located by handling specific constraints. The model and methods are applied to an actual high‐speed railway. Results show that both SAI‐ and ASI‐generated railways have higher NPV values compared to the corresponding railway designed by experienced designers. Sensitivity analysis reveals that SAI is more flexible than ASI in solving actual cases. The convergence of the proposed methods is also discussed. With some changes in input parameters based on locally applicable design standards, the proposed methods are generally applicable to other cases or countries.
Infection of Arabidopsis by cucumber mosaic virus triggers jasmonate‐dependent resistance to aphids that relies partly on the pattern‐triggered immunity factor BAK1
Authors: Tungadi Trisna , Watt Lewis G. , Groen Simon C. , Murphy Alex M. , Du Zhiyou , Pate Adrienne E. , Westwood Jack H. , Fennell Thea G. , Powell Glen , Carr John P.
Published: June 2021

Many aphid‐vectored viruses are transmitted nonpersistently via transient attachment of virus particles to aphid mouthparts and are most effectively acquired or transmitted during brief stylet punctures of epidermal cells. In Arabidopsis thaliana, the aphid‐transmitted virus cucumber mosaic virus (CMV) induces feeding deterrence against the polyphagous aphid Myzus persicae. This form of resistance inhibits prolonged phloem feeding but promotes virus acquisition by aphids because it encourages probing of plant epidermal cells. When aphids are confined on CMV‐infected plants, feeding deterrence reduces their growth and reproduction. We found that CMV‐induced inhibition of growth as well as CMV‐induced inhibition of reproduction of M. persicae are dependent upon jasmonate‐mediated signalling. BRASSINOSTEROID INSENSITIVE1‐ASSOCIATED KINASE1 (BAK1) is a co‐receptor enabling detection of microbe‐associated molecular patterns and induction of pattern‐triggered immunity (PTI). In plants carrying the mutant bak1‐5 allele, CMV induced inhibition of M. persicae reproduction but not inhibition of aphid growth. We conclude that in wildtype plants CMV induces two mechanisms that diminish performance of M. persicae: a jasmonate‐dependent and PTI‐dependent mechanism that inhibits aphid growth, and a jasmonate‐dependent, PTI‐independent mechanism that inhibits reproduction. The growth of two crucifer specialist aphids, Lipaphis erysimi and Brevicoryne brassicae, was not affected when confined on CMV‐infected A. thaliana. However, B. brassicae reproduction was inhibited on CMV‐infected plants. This suggests that in A. thaliana CMV‐induced resistance to aphids, which is thought to incentivize virus vectoring, has greater effects on polyphagous than on crucifer specialist aphids.
Adaptation to coastal soils through pleiotropic boosting of ion and stress hormone concentrations in wild Arabidopsis thaliana
Authors: Busoms Silvia , Terés Joana , Yant Levi , Poschenrieder Charlotte , Salt David E.
Published: June 2021

Local adaptation in coastal areas is driven chiefly by tolerance to salinity stress. To survive high salinity, plants have evolved mechanisms to specifically tolerate sodium. However, the pathways that mediate adaptive changes in these conditions reach well beyond Na+.

Here we perform a high‐resolution genetic, ionomic, and functional study of the natural variation in Molybdenum transporter 1 (MOT1) associated with coastal Arabidopsis thaliana accessions. We quantify the fitness benefits of a specific deletion‐harbouring allele (MOT1DEL) present in coastal habitats that is associated with lower transcript expression and molybdenum accumulation.

Analysis of the leaf ionome revealed that MOT1DEL plants accumulate more copper (Cu) and less sodium (Na+) than plants with the noncoastal MOT1 allele, revealing a complex interdependence in homeostasis of these three elements. Our results indicate that under salinity stress, reduced MOT1 function limits leaf Na+ accumulation through abscisic acid (ABA) signalling. Enhanced ABA biosynthesis requires Cu. This demand is met in Cu deficient coastal soils through MOT1DEL increasing the expression of SPL7 and the copper transport protein COPT6.

MOT1DEL is able to deliver a pleiotropic suite of phenotypes that enhance salinity tolerance in coastal soils deficient in Cu. This is achieved by inducing ABA biosynthesis and promoting reduced uptake or better compartmentalization of Na+, leading to coastal adaptation.
Towards a statistically robust determination of minimum water potential and hydraulic risk in plants
Authors: Martínez‐Vilalta Jordi , Santiago Louis S. , Poyatos Rafael , Badiella Llorenç , de Cáceres Miquel , Aranda Ismael , Delzon Sylvain , Vilagrosa Alberto , Mencuccini Maurizio
Published: June 2021

Minimum water potential (Ψmin) is a key variable for characterizing dehydration tolerance and hydraulic safety margins (HSMs) in plants. Ψmin is usually estimated as the absolute minimum tissue Ψ experienced by a species, but this is problematic because sample extremes are affected by sample size and the underlying probability distribution.

We compare alternative approaches to estimate Ψmin and assess the corresponding uncertainties and biases; propose statistically robust estimation methods based on extreme value theory (EVT); and assess the implications of our results for the characterization of hydraulic risk.

Our results show that current estimates of Ψmin and HSMs are biased, as they are strongly affected by sample size. Because sampling effort is generally higher for species living in dry environments, the differences in current Ψmin estimates between these species and those living under milder conditions are partly artefactual. When this bias is corrected using EVT methods, resulting HSMs tend to increase substantially with resistance to embolism across species.

Although data availability and representativeness remain the main challenges for proper determination of Ψmin, a closer look at Ψ distributions and the use of statistically robust methods to estimate Ψmin opens new ground for characterizing plant hydraulic risks.
A philosophical analysis of anti‐intellectualism in nursing: Newman’s view of a university education
Authors: Racine Louise , Vandenberg Helen
Published: June 2021

Canadian and international nursing educators are increasingly concerned with the quality of university nursing education. Contemporary nursing education is fraught by a growing anti‐intellectualism coupled with the dominance of neoliberalism and corporate university business culture. Amid these challenges, nursing schools must prepare nurses to provide care in an era compounded by social and health inequities. The purpose of this paper was to explore the philosophical and contextual factors influencing anti‐intellectualism in nursing education. We use John Henry Newman's view of the purpose of a university education as a heuristic perspective to examine anti‐intellectualism in nursing. We contend that the ideological worship of technological advances, a culture of consumerism, quality improvement and risk management, the primacy of doing over thinking, competency‐based curricula and business models rooted in neoliberal financial policies reinforce anti‐intellectualism in nursing. Anti‐intellectualism is a complex issue to address within the corporate university culture. We propose multiple strategies at the disciplinary, university and sociopolitical levels to decrease anti‐intellectualism. Counteracting anti‐intellectualism requires critical thinking, praxis and emancipation. Nurses should critically examine this anti‐intellectual trend as it limits the advancement of the discipline and marginalizes its contributions within the academy. If nurses do not address this challenge, the survival of nursing as an academic discipline may be jeopardized.
Harnessing the power to bridge different worlds: An introduction to posthumanism as a philosophical perspective for the discipline
Authors: Adam Simon , Juergensen Linda , Mallette Claire
Published: June 2021

Although it is argued that social justice is a core concern for the discipline, nursing has not generally played a leadership role in the responses to many of the greatest social problems of our time. These include the accelerated rate of climate change, pandemic threats, systemic racism, growing health and social inequities, and the regulation of new technologies to ensure an equitable future ‘for all.’ In nursing codes of ethics, administration, education, policies, and practice, social justice is often claimed to be a core value, yet it is rarely contextualized by philosophical or theoretical underpinnings. It appears that nurses’ commitment to social justice may stem more from a penchant for ‘doing good’ than an attempt to explore, understand, and enact what is meant by social justice from an ontological, epistemological, and methodological perspective. We contend that the dominance of a human science perspective in nursing contributes to a narrow definition of health and relegates many issues central to social justice to the margins of nurses’ care. In this article, we explore how the focus on ‘the human’ in the human science perspective may not only be limiting the capacity of nurses to develop strategies to adequately address social injustice, but in some instances, direct nurses to contribute to their very reproduction. We suggest that a critical interrogation of this human‐centric hegemony can identify avenues of rupture and introduce posthumanism as an additional philosophical perspective for consideration to help bridge the human‐social divide.