bluuebunny/crossref_metadata_2025 huggingface dataset:
Sunset Inn: three-phase case study before, during and after the wrath of COVID-19
Authors: Khan Bukhari
Published: January 2021

Purpose

The purpose of this case study is to explore the first-hand aftermath of the effects bestowed upon the travel industry by the coronavirus. To connect the effects to a real-life example, a particular hotel is being used as the reference point. Its ups, its downs and its day-to-day operations are reflected upon within the case study.

Design/methodology/approach

A real-life approach to this case was taken. To simplify and to further explain each of the concepts presented, mentioned and explained, the author referred back to the subject hotel, which has experienced its ups and downs owing to the coronavirus pandemic. The author has also discussed the benefits and drawbacks of each of the concepts explained within the case as well, along with real-life examples of other hotels and their specific experiences.

Findings

It was founded that economy hotels are faring better than most, if not all midscale and upscale properties. This success is attributed to multiple reasons: the availability and acceptability of contactless payments through Cash App and Venmo, the exterior access to the guestrooms, through the parking lot, rather than a hallway.

Originality/value

This case, in the author’s humble opinion, is as original as can be. Many concepts that are prominent within the business were mentioned, and further explained them and their relevancy by connecting it to the subject hotel, which too has experienced the effects of coronavirus – and the effects of the executive actions that were implemented in response of the virus.
Unravelling processes of alliance capability development: longitudinal processual insights from an emerging country multinational enterprise
Authors: Pereira Vijay , Patnaik Swetketu , Roohanifar Mohammad , Baliga Ram
Published: January 2021

Purpose

The purpose of this paper is to explore and unbundle the complex processes underpinning development of alliance capabilities, particularly in the context of emerging country multinational enterprises. More specifically, this paper focuses on how firms internalize and translate knowledge generated from experiences gained by participating in international collaborations.

Design/methodology/approach

The authors adopt an exploratory case study approach to undertake in-depth processual analysis of alliance capability development in an Indian biopharmaceutical company. The authors focused their analysis on the initial four international alliances the company formed and identified key elements pertaining to alliance capabilities that the company internalized and those that it could not, as this was key in understanding alliance capability.

Findings

The research shows that based on experiences from previous alliances, the Indian organization was able to overhaul its negotiation and governance designing processes and practices as well as made robust changes to its internal communication and coordination practices. Interestingly, the company organization, however, did not make any significant changes to its processes and practices regarding partner selection.

Practical implications

The results from our study can be used by managers to develop processes and practices when it comes to developing alliance capabilities.

Originality/value

The paper is novel, as it addresses two specific gaps in the nascent alliance capability literature. First, it provides insights on how different constituent elements/aspects of alliance capability actually develop and integrate within the organizational system over time, and in the process, the paper identifies that some aspects are better internalized as compared to other aspects. Second, by focusing the attention on an Indian biopharmaceutical company, the authors attempt to address a gap in alliance capability development research, which has been neglected in emerging country multinational entities.
Flex−Buildings Designed to Change
Authors: Vink Jacques
Published: January 2021

Flex−buildings are buildings which are literally designed to change. A flex−building must be able to accept different infills and its users must be able to easily adapt their surroundings.

Flexibility is defined as the capacity of a building to undergo modifications and accept changes of function with limited structural interventions. More than 40% of the activities housed in a flex building can continue to function during modification.

Studies into flex−buildings (commissioned by the Dutch Government) have elicited a number of insights. These are not hard−and−fast conclusions but more in the region of statements and reminders for those involved with flex−buildings.

These studies show that it takes more than civil engineering to successfully realise such buildings. Aspects of use and management are at least as important. Besides, it requires designers who are willing to let go of their design after it is finished. For the result is not a completed ‘architectural’ product but a continually changing object.

Following insights (among others) will be illustrated with built and unbuilt projects in the Netherlands.

• The façade design, for example, figures prominently in designing flexible buildings. It makes special demands on the design’s presentation during the design process, as the building can assume different appearances over time. The double facade is a promising concept that allows for expressive and/or open facades in flexible buildings. It can also help to reduce a building’s energy consumption.

• Also by deliberately incorporating excessive space and construction a building has the necessary leeway to accommodate future developments. A building’s flexibility is enhanced by oversize in structure as well as space.

• A big multi−use building in Rotterdam (H. A. Maaskant / W. van Tijen (1951)) and recent projects of RUIMTELAB are presented as case−studies. These are an inspiration for architects and planners looking for design tools to help achieve an open architecture.
New Trends in the Dutch Housing Market
Authors: Boelhouwer Peter , Hoekstra Joris
Published: January 2021

Every few years the planning agencies in the Netherlands draw up a prognosis for the future housing needs on the basis of economic and demographic scenarios. It is our contention that, in applying this approach, the agencies neglect to take sufficient account of the influence of cultural dynamics. Against this background, a recent recommendatory report by the Dutch Council for Housing, Spatial Planning and the Environment (VROM-raad 2009) drew attention to three socio-cultural trends which are currently manifesting themselves on the Dutch housing market:

1. A growing interest in living with like-minded people and in common-interest housing concepts;

2. The rise of transnational living (permanently or temporarily living abroad) and people having multiple residences;

3. An increasing mix of housing and other functions and services (care, energy, leisure, retail), which is opening up the housing market for new players.

This contribution explores the background and the expressions of these three trends that will have a significant influence on the demand for housing in the future, in spatial terms as well as with regard to quantity and quality. It turns out that the trends raise new dilemmas in spatial planning and housing policy. In order to solve these dilemmas, a different way of thinking is needed.
Is competition a cure for confusion? Evidence from the residential mortgage market
Authors: Malliaris Steven , Rettl Daniel A. , Singh Ruchi
Published: January 2021

Using the National Survey of Mortgage Originations, we document that borrowers who are more financially sophisticated (measured by their self‐reported understanding of the mortgage process) and more exposed to competition (measured by the number of lenders they considered) pay lower mortgage rate spreads. Yet, competition is not a substitute for sophistication: the benefits of competition accrue to sophisticates as well as to naïfs. Our results complement those from the literature detailing the limits of advice and education, and collectively they paint a pessimistic view about the prospects for simple interventions to close the mortgage rate gap between the informed and the naive.
The readiness of pediatric rheumatology patients and their parents to transition to adult‐oriented treatment
Authors: Sönmez Hafize Emine , Koç Rahime , Karadağ Şerife Gül , Aktay Ayaz Nuray
Published: January 2021

Introduction

Transition is a planned process of pediatric patients from child‐centered to adult‐oriented treatment. Transitional care for patients with chronic diseases is essential. The present study aimed to evaluate the readiness of patients with rheumatic diseases and their parents for transition process.

Method

This is a cross‐sectional, single‐center study. All patients and their parents were questioned about their awareness of and willingness to undergo transitional care. Transition Readiness Assessment Questionnaire (TRAQ) was applied to all the participants. TRAQ is a tool for measuring readiness for transitional care in adolescents with chronic diseases. TRAQ includes 20 items that are divided into 2 domains: self‐management and self‐advocacy.

Results

A total of 157 (87 girls/70 boys) patients and their parents were enrolled. Of them 64 were diagnosed with familial Mediterranean fever, 52 with juvenile idiopathic arthritis, 21 with systemic lupus erythematosus, and 20 with Behçet's disease. The median age of the patients was 16 years (15‐18). However, all patients and parents accepted that transition to adult‐oriented care is necessary; only one‐third of them were aware about transitional care. Eighty (50.9%) patients and 147 (93.6%) of the parents stated that they were wishing to continue pediatric rheumatology treatment. The mean TRAQ self‐management domain and self‐advocacy domain total scores in the patients were 1.76 ± 0.51 and 1.72 ± 0.49, respectively (P = .48). The mean TRAQ total score was not different between patients and parents. When we assessed the factors affecting transition process, the TRAQ score was lower among patients with active disease, and requiring hospitalization during the previous year.

Conclusion

Assessment od the readiness of patients with chronic rheumatic diseases for transition care will increase the awareness of patients and their parents as well, and provide determination of the optimal time for transition.
Effects of a brief alcohol intervention addressing the full spectrum of drinking in an adult general population sample: a randomized controlled trial
Authors: Baumann Sophie , Staudt Andreas , Freyer‐Adam Jennis , Bischof Gallus , Meyer Christian , John Ulrich
Published: January 2021

Background and aims

Evidence for efficacy of brief alcohol interventions (BAIs) is mainly limited to primary care and at‐risk drinkers. The aim was to test the efficacy of a BAI addressing the full spectrum of alcohol use in a general population sample and across alcohol risk groups.

Design

Two‐parallel‐group randomized controlled trial (allocation ratio 1:1) with post‐baseline assessments at months 3, 6 and 12.

Setting

One municipal registry office in Germany responsible for registration, passport and vehicle admission issues.

Participants

A total of 1646 proactively recruited 18–64‐year‐old adults with past year alcohol use (56% women, 66% low‐risk drinkers) were randomized to intervention (n = 815) or control (n = 831).

Intervention and comparator

The intervention consisted of assessment plus computer‐generated individualized feedback letters at baseline and months 3 and 6. Comparator was assessment only.

Measurements

Primary outcome was change in the self‐reported number of drinks/week from baseline to 12 months. Changes at 3 and 6 months were secondary outcomes. Moderator was alcohol risk group (low‐risk versus at‐risk drinking) according to the Alcohol Use Disorders Identification Test–Consumption, with scores from 1‐3 (women) and from 1‐4 (men) indicating low‐risk drinking.

Findings

For the whole sample, significant group differences were observed neither at 12‐month follow‐up [incidence rate ratio (IRR) = 1.01, 95% confidence interval (CI) = 0.87–1.17, Bayes factor (BE) = 0.52] nor at previous assessments (month 3: IRR = 1.01, 95% CI = 0.92–1.12, BE = 0.41; month 6: IRR = 0.93, 95% CI = 0.81–1.07, BE = 1.10). Moderator analyses revealed that low‐risk drinkers were more likely to benefit from BAI only at month 6 than at‐risk drinkers (IRR = 0.77, 95% CI = 0.70–0.86).

Conclusions

In a randomized controlled trial, there was no clear evidence for efficacy of a computer‐based brief alcohol intervention in a general population sample, but there was some evidence of medium‐term benefits in the large but understudied group of low‐risk drinkers.
Acidity, fluoride and silver ion concentrations in silver diamine fluoride solutions: a pilot study
Authors: Patel J , Foster D , Smirk M , Turton B , Anthonappa R
Published: January 2021

Background

There has been renewed interest in the use of silver diamine fluoride (SDF) for the management of carious lesions in high‐risk groups. Previous studies have found a difference in clinical efficacy among different concentrations of SDF and discrepancies between ionic concentrations of fluoride (F) and silver (Ag) in SDF preparations. The aim of this study was to measure the free F, Ag ion concentrations and pH of a variety of commercially available SDF preparations.

Methods

Seven SDF products used globally were evaluated for F and Ag ion concentrations using a calibrated ion‐selective electrode and optical emission spectrometry respectively. Acidity was determined with a pH electrode.

Results

The 30% SDF solution contained almost half the F concentration and a much higher Ag concentration than expected (16 343 ppmF and 246 000 ppmAg). Comparatively, the mean F concentration of the remaining six 38% solutions was 74 802 ppm (expected mean 44 800 ppm) ranging from 36 457 ppm to 120 760 ppm. The mean Ag concentration was 326 000 ppm (expected mean 253 870 ppm) and ranged from 246 000 ppm to 425 451 ppm. All solutions were found to be neutral or mildly alkaline in nature (pH 7–10.3).

Conclusions

Wide variations between claimed and measured F and Ag ion concentrations exist among the different brands of commercially available SDF products.
Are high elevation crag lizards sensitive to climate change?
Authors: Perold Vonica , Ferguson Jan Willem H. , Verburgt Luke , Malherbe Johan B.
Published: January 2021

Crag lizards are restricted to montane areas where biota are strongly exposed to the effects of climate change. We investigated the factors shaping the distribution of Drakensberg crag lizards (Pseudocordylus melanotus melanotus; Cordylidae) by quantifying their elevational ranges, availability of shelter and prey as well as the thermal environment at three elevations. We recorded expected body temperatures using copper models of the lizards at each elevation in the field and in the laboratory, estimating the duration for which lizards must shelter from high temperatures. This correlated strongly with field observations of lizard activity during winter, spring and summer. Our models predicted that at lower elevations, lizards would shelter for longer periods each day, resulting in a marked reduction in time available for essential activities such as feeding and breeding, possibly explaining why these animals do not occur at lower elevations. The distribution and survival of these animals therefore appear to be impacted by the degree to which daytime temperatures limit their activity. Modelling future climate change scenarios at the high elevation site indicates that crag lizards would be resilient against small to moderate warming reflected by RCP4.5 climate change predictions, but populations are unlikely to persist under conditions predicted in the RCP8.5 scenario. This study is important as, unlike broader‐scope studies that cannot quantify climate change impacts on individual species, we combine detailed field data with laboratory measurements and modelling of a single species to assess the ecological constraints to which crag lizards are exposed.
Molecular markers of type 2 airway inflammation are similar between eosinophilic severe asthma and eosinophilic chronic obstructive pulmonary disease
Authors: Fricker Michael , McDonald Vanessa M. , Winter Natasha A. , Baines Katherine J. , Wark Peter A. B. , Simpson Jodie L. , Gibson Peter G.
Published: January 2021

Background

Airway and systemic eosinophilia are important treatable traits in both severe asthma and COPD. The molecular basis of eosinophilia in COPD is poorly understood but could involve type 2 cytokines (IL5, IL13) and prostaglandin D2 (PGD2).

Methods

This study included non‐obstructive airways disease (OAD) controls (n = 19), a COPD cohort (n = 96) and a severe asthma cohort (n = 84). Demographics, exacerbation history, disease impact (SGRQ) and spirometry were assessed. Participants were categorized as eosinophilic using either sputum eosinophil proportion (≥3%) or blood eosinophil count (≥300/μL). Sputum type 2 inflammatory measures included PGD2 by ELISA and gene expression (qPCR) of IL5, IL13 and the haematopoietic PGD2 synthase (HPGDS).

Results

Type 2 markers did not differ across groups except HPGDS mRNA which was highest in non‐OAD controls and lowest in COPD. IL5 and IL13 mRNA and PGD2 levels were significantly increased in eosinophilic vs non‐eosinophilic severe asthma but did not differ between eosinophilic COPD and eosinophilic severe asthma or non‐eosinophilic COPD. HPGDS expression was higher in eosinophilic severe asthma compared with eosinophilic COPD. Results were similar using sputum or blood eosinophil cut‐offs. Sputum IL5 and IL13 were highly intercorrelated in severe asthma (r = 0.907, p < 0.001) and COPD (r = 0.824, p < 0.001), were moderately correlated with sputum eosinophils in severe asthma (IL5 r = 0.440, p < 0.001; IL13 r = 0.428, p < 0.001) and were weakly correlated in COPD (IL5 r = 0.245, p < 0.05; IL13 r = 0.317, p < 0.05).

Conclusions

Molecular markers of type 2 airway inflammation do not differ between eosinophilic asthma and eosinophilic COPD; however, the relationship between eosinophilia and type 2 airway markers appears weaker in COPD than in severe asthma.
Banking crises and economic growth in developing countries: Why privileging foreign direct investment over external debt?
Authors: Gaies Brahim , Nabi Mahmoud‐Sami
Published: January 2021

The impact of external financing on the economies of developing countries is still a subject of debate among economists and policy makers. The objective of this paper is to contribute to this debate by shedding light on the interaction between foreign direct investment (FDI) and external debt. To this end, we begin by formulating an overlapping generation growth model that integrates a banking sector and find two complementary results. First, we show that external financing boosts investment projects and accelerates the dynamic of capital accumulation and economic growth. The second one mitigates this channel by showing two opposite indirect effects of external debt and FDI. Indeed, while external debt financing increases the vulnerability to a bank run that generates a recessionary impact on economic growth, FDI attenuates this recessionary impact and plays the role of a shock absorber. We empirically confirm these results for 67 developing countries over the period 1972–2015 using the GMM estimation of growth models and panel‐logit models to predict the determinants of banking crises. Hence, this study provides a comprehensive assessment of developing countries’ involvement in financial globalization and offers recommendations for their future international economic policies.
Combining mesenchymal stem cells with serelaxin provides enhanced renoprotection against 1K/DOCA/salt‐induced hypertension
Authors: Li Yifang , Shen Matthew , Ferens Dorota , Broughton Brad R.S. , Murthi Padma , Saini Sheetal , Widdop Robert E. , Ricardo Sharon D. , Pinar Anita A. , Samuel Chrishan S.
Published: January 2021

Background and Purpose

Fibrosis is a hallmark of chronic kidney disease (CKD) that significantly contributes to renal dysfunction, and impairs the efficacy of stem cell‐based therapies. This study determined whether combining bone marrow‐derived mesenchymal stem cells (BM‐MSCs) with the renoprotective effects of recombinant human relaxin (serelaxin) could therapeutically reduce renal fibrosis in mice with one kidney/deoxycorticosterone acetate/salt (1K/DOCA/salt)‐induced hypertension, compared with the effects of the ACE inhibitor, perindopril.

Experimental Approach

Adult male C57BL/6 mice were uni‐nephrectomised and received deoxycorticosterone acetate and saline to drink (1K/DOCA/salt) for 21 days. Control mice were uni‐nephrectomised but received water over the same time period. Sub‐groups of 1K/DOCA/salt‐injured mice (n = 5–8 per group) were treated with either serelaxin (0.5 mg·kg−1·day−1) or BM‐MSCs (1 × 106 per mouse) alone; both treatments combined (with 0.5 × 106 or 1 × 106 BM‐MSCs per mouse); or perindopril (2 mg·kg−1·day−1) from days 14–21.

Key Results

1K/DOCA/salt‐injured mice developed elevated BP and hypertension‐induced renal damage, inflammation and fibrosis. BM‐MSCs alone reduced the injury‐induced fibrosis and attenuated BP to a similar extent as perindopril. Serelaxin alone modestly reduced renal fibrosis and effectively reduced tubular injury. Strikingly, the combined effects of BM‐MSCs (at both doses) with serelaxin significantly inhibited renal fibrosis and proximal tubular epithelial injury while restoring renal architecture, to a greater extent than either therapy alone, and over the effects of perindopril.

Conclusion and Implications

Combining BM‐MSCs and serelaxin provided broader renoprotection over either therapy alone or perindopril and might represent a novel treatment for hypertensive CKD.
Nuciferine protects against folic acid‐induced acute kidney injury by inhibiting ferroptosis
Authors: Li Danyu , Liu Bing , Fan Yumei , Liu Ming , Han Bihui , Meng Yanxiu , Xu Xiao , Song Zhiyuan , Liu Xiaopeng , Hao Qiang , Duan Xianglin , Nakai Akira , Chang Yanzhong , Cao Pengxiu , Tan Ke
Published: January 2021

Background and Purpose

Acute kidney injury is a common clinical problem with no definitive or specific treatment. Therefore, the molecular mechanisms of acute kidney injury must be fully understood to develop novel treatments. Nuciferine, a major bioactive compound isolated from the lotus leaf, possesses extensive pharmacological activities. Its effect on folic acid‐induced acute kidney injury, however, remains unknown. Here, we aimed to clarify the pharmacological effects of nuciferine and its mechanisms of action in acute kidney injury.

Experimental Approach

The effects of nuciferine on folic acid‐induced acute kidney injury in mice were investigated. HK‐2 human proximal tubular epithelial cells and HEK293T HEK cells were used to evaluate the protective effect of nuciferine on RSL3‐induced ferroptosis.

Key Results

Nuciferine treatment mitigated the pathological alterations, ameliorated inflammatory cell infiltration and improved kidney dysfunction in mice with folic acid‐induced acute kidney injury. In HK‐2 and HEK293T cells, nuciferine significantly prevented RSL3‐induced ferroptotic cell death. Mechanistically, nuciferine significantly inhibited ferroptosis by preventing iron accumulation and lipid peroxidation in vitro and in vivo. Moreover, knockdown of glutathione (GSH) peroxidase 4 (GPX4) abolished the protective effect of nuciferine against ferroptosis.

Conclusion and Implications

Nuciferine ameliorated renal injury in mice with acute kidney injury, perhaps by inhibiting the ferroptosis. Nuciferine may represent a novel treatment that improves recovery from acute kidney injury by targeting ferroptosis.
The ratio of ursodeoxycholyltaurine to 7‐oxolithocholyltaurine serves as a biomarker of decreased 11β‐hydroxysteroid dehydrogenase 1 activity in mouse
Authors: Weingartner Michael , Stücheli Simon , Kratschmar Denise V. , Birk Julia , Klusonova Petra , Chapman Karen E. , Lavery Gareth G. , Odermatt Alex
Published: January 2021

Background and Purpose

11β‐Hydroxysteroid dehydrogenase 1 (11β‐HSD1) regulates tissue‐specific glucocorticoid metabolism and its impaired expression and activity are associated with major diseases. Pharmacological inhibition of 11β‐HSD1 is considered a promising therapeutic strategy. This study investigated whether alternative 7‐oxo bile acid substrates of 11β‐HSD1 or the ratios to their 7‐hydroxy products can serve as biomarkers for decreased enzymatic activity.

Experimental Approach

Bile acid profiles were measured by ultra‐HPLC tandem‐MS in plasma and liver tissue samples of four different mouse models with decreased 11β‐HSD1 activity: global (11KO) and liver‐specific 11β‐HSD1 knockout mice (11LKO), mice lacking hexose‐6‐phosphate dehydrogenase (H6pdKO) that provides cofactor NADPH for 11β‐HSD1 and mice treated with the pharmacological inhibitor carbenoxolone. Additionally, 11β‐HSD1 expression and activity were assessed in H6pdKO‐ and carbenoxolone‐treated mice.

Key Results

The enzyme product to substrate ratios were more reliable markers of 11β‐HSD1 activity than absolute levels due to large inter‐individual variations in bile acid concentrations. The ratio of the 7β‐hydroxylated ursodeoxycholyltaurine (UDC‐Tau) to 7‐oxolithocholyltaurine (7oxoLC‐Tau) was diminished in plasma and liver tissue of all four mouse models and decreased in H6pdKO‐ and carbenoxolone‐treated mice with moderately reduced 11β‐HSD1 activity. The persistence of 11β‐HSD1 oxoreduction activity in the face of H6PD loss indicates the existence of an alternative NADPH source in the endoplasmic reticulum.

Conclusions and Implications

The plasma UDC‐Tau/7oxo‐LC‐Tau ratio detects decreased 11β‐HSD1 oxoreduction activity in different mouse models. This ratio may be a useful biomarker of decreased 11β‐HSD1 activity in pathophysiological situations or upon pharmacological inhibition.

LINKED ARTICLES

This article is part of a themed issue on Oxysterols, Lifelong Health and Therapeutics. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.16/issuetoc
The anti‐parasitic drug miltefosine suppresses activation of human eosinophils and ameliorates allergic inflammation in mice
Authors: Knuplez Eva , Kienzl Melanie , Trakaki Athina , Schicho Rudolf , Heinemann Akos , Sturm Eva M. , Marsche Gunther
Published: January 2021

Background and Purpose

Miltefosine is an alkylphosphocholine drug with proven effectiveness against various types of parasites and cancer cells. Miltefosine is not only able to induce direct parasite killing but also modulates host immunity, for example by reducing the severity of allergies in patients. To date, there are no reports on the effect of miltefosine on eosinophils, central effector cells involved in allergic inflammation.

Experimental Approach

We tested the effect of miltefosine on the activation of human eosinophils and their effector responsesin vitroand in mouse models of eosinophilic migration and ovalbumin‐induced allergic lung inflammation.

Key Results

The addition of miltefosine suppressed several eosinophilic effector reactions such as CD11b up‐regulation, degranulation, chemotaxis and downstream signalling. Miltefosine significantly reduced the infiltration of immune cells into the respiratory tract of mice in an allergic cell recruitment model. Finally, in a model of allergic inflammation, treatment with miltefosine resulted in an improvement of lung function parameters.

Conclusion and Implications

Our observations suggest a strong modulatory activity of miltefosine in the regulation of eosinophilic inflammationin vitroandin vivo. Our data underline the potential efficacy of miltefosine in the treatment of allergic diseases and other eosinophil‐associated disorders and may raise important questions regarding the immunomodulatory effect of miltefosine in patients treated for leishmania infections.
CircPVT1 promotes progression in clear cell renal cell carcinoma by sponging miR‐145‐5p and regulating TBX15 expression
Authors: Zheng Zaosong , Chen Zhiliang , Zhong Qiyu , Zhu Dingjun , Xie Yingwei , Shangguan Wentai , Xie Wenlian
Published: January 2021

Emerging evidence revealed that circular RNAs (circRNAs) play significant roles in regulating tumorigenesis and cancer progression. However, few circRNAs were well characterized in clear cell renal cell carcinoma (ccRCC). We found that circPVT1 was significantly upregulated in ccRCC tissues and positively associated with the clinical stage. The Area Under Curve of tissue and serum circPVT1 expression in ccRCC were 0.93 and 0.86, respectively. Importantly, we demonstrated that circPVT1 promoted ccRCC growth and metastasis in vitro and in vivo. We also found that circPVT1 directly binds to miRNA‐145‐5p via the Biotin‐labelled miRNA pulldown assay and dual‐luciferase reporter assay, and miR‐145‐5p inhibitor significantly attenuated the effect of circPVT1 knockdown on ccRCC cells. Moreover, through RNA sequencing and bioinformatics analysis, we demonstrated that TBX15 was regulated by the circPVT1/miR‐145‐5p axis and predicted poor prognosis in ccRCC. These findings suggest that circPVT1 promotes ccRCC growth and metastasis through sponging miR‐145‐5p and regulating downstream target TBX15 expression. The circPVT1/miR‐145‐5p/TBX15 axis might be a potential diagnostic marker and therapeutic target in ccRCC.
Selective inhibition of prostaglandin D2 biosynthesis in human mast cells to overcome need for multiple receptor antagonists: Biochemical consequences
Authors: Johnsson Anna‐Karin , Choi Jeong‐Hee , Rönnberg Elin , Fuchs David , Kolmert Johan , Hamberg Mats , Dahlén Barbro , Wheelock Craig E. , Dahlén Sven‐Erik , Nilsson Gunnar
Published: January 2021

Background

The major mast cell prostanoid PGD2 is targeted for therapy of asthma and other diseases, because the biological actions include bronchoconstriction, vasodilation and regulation of immune cells mediated by three different receptors. It is not known if the alternative to selectively inhibit the biosynthesis of PGD2 affects release of other prostanoids in human mast cells.

Objectives

To determine the biochemical consequences of inhibition of the hematopoietic prostaglandin D synthase (hPGDS) PGD2 in human mast cells.

Methods

Four human mast cell models, LAD2, cord blood derived mast cells (CBMC), peripheral blood derived mast cells (PBMC) and human lung mast cells (HLMC), were activated by anti‐IgE or ionophore A23187. Prostanoids were measured by UPLC‐MS/MS.

Results

All mast cells almost exclusively released PGD2 when activated by anti‐IgE or A23187. The biosynthesis was in all four cell types entirely initiated by COX‐1. When pharmacologic inhibition of hPGDS abolished formation of PGD2, PGE2 was detected and release of TXA2 increased. Conversely, when the thromboxane synthase was inhibited, levels of PGD2 increased. Adding exogenous PGH2 confirmed predominant conversion to PGD2 under control conditions, and increased levels of TXB2 and PGE2 when hPGDS was inhibited. However, PGE2 was formed by non‐enzymatic degradation.

Conclusions

Inhibition of hPGDS effectively blocks mast cell dependent PGD2 formation. The inhibition was associated with redirected use of the intermediate PGH2 and shunting into biosynthesis of TXA2. However, the levels of TXA2 did not reach those of PGD2 in naïve cells. It remains to determine if this diversion occurs in vivo and has clinical relevance.
Evaluation of interleukin‐29 in autoimmune and inflammatory thyroid diseases
Authors: Falkowski Bogusz , Szczepanek‐Parulska Ewelina , Krygier Aleksandra , Wrotkowska Elzbieta , Ruchala Marek
Published: January 2021

Objective

Interleukins play an important role in the development of autoimmune disorders. The aim of this study was to compare the concentration of interleukin‐29 (IL‐29) between healthy controls (CS) and patients with selected thyroid disorders: Graves’ disease (GD), Hashimoto's thyroiditis (HT) and subacute thyroiditis (SAT).

Design and methods

The following parameters were examined in the group of 95 individuals (45 with GD, 22 with HT, 28 with SAT) and 72 CS: thyroid hormones and autoantibodies, inflammatory markers and the concentration of IL‐29 in serum.

Results

The concentration of IL‐29 in the GD subgroup was higher than that in the CS subgroup [264.0 (62.5‐1018.0) vs. 62.5 (62.5‐217.0) pg/mL, P = .001]. We found no differences in IL‐29 concentrations between the CS and HT or SAT subgroups. Multivariable linear regression analysis indicated that IL‐29 was a statistically significant independent predictor of GD presence (r = 0.24; P = .003) after adjustment for TRAb (R2 = 0.45; P < .001). The ROC analysis of IL‐29 at GD diagnosis revealed an IL‐29 cut‐off of 123 pg/mL (sensitivity: 0.689 and specificity: 0.625) as the best value, which significantly indicated the presence of GD [area under the ROC curve (AUC): 0.676; 95% confidence interval (CI): 0.574‐0.778, P < .001].

Conclusion

This is the first study to demonstrate elevated IL‐29 serum levels in patients with GD. Our results suggest that IL‐29 might be engaged in one of the pathogenetic pathways of GD, but no HT and SAT. Future studies are required to evaluate the potential of the protein as a therapeutic target in GD.
Is implant surgery a risk factor for osteonecrosis of the jaw in older adult patients with osteoporosis? A national cohort propensity score‐matched study
Authors: Ryu Jae‐In , Kim Ha‐Young , Kwon Yong‐Dae
Published: January 2021

Objectives

This study aimed to investigate the association between dental implant therapy and osteonecrosis of the jaw (ONJ) in osteoporotic patients and the relationship between tooth extraction, dental implantation, and ONJ.

Material and Methods

This retrospective cohort study used the Customized Health Information Data from the National Health Insurance Corporation in South Korea. The study population included patients older than 70 years with a history of osteoporosis; the cases included patients who had undergone dental implant surgery between July 2014 and July 2016 with specific procedure codes. The case and control cohorts were stratified by tooth extraction because it was the strongest risk factor to consider in this study. Each group of patients was matched using the propensity score. To investigate the relationship between dental implants and ONJ, a Cox proportional hazard model was applied to socio‐economic factors, comorbidities, and bisphosphonates (BPs). All analyses were conducted using SAS statistical software.

Results

Based on the fully adjusted model, the propensity score‐matched osteoporosis patients with dental implants had a 0.51 times hazard ratio of osteonecrosis. On the contrary, tooth extraction was associated with a higher risk of ONJ (HR = 5.89). The patients with rheumatoid arthritis (RA) and those using BPs had a higher HR, respectively, 6.80 and 4.09 HR (p < .001).

Conclusions

Dental implantation was not a risk factor and patients with implants show rather lower ratios. However, older osteoporotic Korean patients who had undergone tooth extraction had higher risks of ONJ. A significantly higher risk of ONJ was associated with RA and BPs as well.
Assessment of dwarf mistletoe (Arceuthobium sichuanense) infection in spruce trees by using hyperspectral data
Authors: Xiong Dianguang , Huang Huayi , Wang Zezhong , Li Zhouyuan , Tian Chengming
Published: January 2021

Dwarf mistletoe (Arceuthobiumspp.,Viscaceae) (DM), a hemiparasitic plant, is nutritionally dependent upon its host tree and causes tree mortality in forests worldwide. Dwarf mistletoe infection results in physiological changes in the host, eventually causing the death of the host tree. In this study, we evaluated the changes in leaf reflectance of spruce trees,Picea crassifolia, infected by DM (Arceuthobium sichuanense) with ground‐based hyperspectral technology. A total of 112 sample sites were selected for analysis in the eastern part of Qinghai Province, China, including healthy spruce tree, light DM‐infected spruce tree, moderate DM‐infected spruce tree and high DM‐infected spruce tree in each site. The results showed that leaf reflectance was significantly different among healthy spruce, DM‐infected spruce, DM and dead spruce in the near‐infrared regions ranging from ~750 to 900 nm. Dwarf mistletoe infection resulted in the increase of leaf reflectance of host tree, and the intensity of DM infection was positively related to reflectance. However, five selected hyperspectral indices that commonly used to estimate the physiological status of plants (carotenoid reflectance index, photochemical reflectance index, normalized difference vegetation index, structure‐insensitive pigment index and water index) were not linearly correlated with the intensity of DM infection. Collectively, the hyperspectral characteristics of spruce infected by DM can be potentially used to detect DM‐induced changes on a landscape scale with satellite remote sensing, which can be used as an efficient advanced tool for DM disease monitoring.
What Accounts for the Emergence of a New Interaction Pattern? On Generative Mechanisms, Constitutive Rules and Charging Routines
Authors: Iannacci Federico , Resca Andrea
Published: January 2021

Drawing on the notion of generative mechanisms as constitutive rules, this paper advocates a shift away from the notion of routines as sources of ongoing change and towards a rule‐based understanding of routines as institutional facts. While the recent practice turn to routines studies has highlighted sources of endogenous change, this paper adopts a Critical Realist stance to investigate exogenous forces that account for the emergence of a new routine. To this end, the paper endeavours to analyse the passing of new legislation in the criminal justice system of England and Wales. By examining what makes the rules of the game change between the Police and the Crown Prosecution Service, the paper explains an instance of institutionalisation in the making. Theoretical and practical implications are discussed. Our contribution stresses that constitutive rules play a pivotal role for recognising, identifying and labelling organisational routines, thus generating order, stability and patterning.
Long‐term effects of pallidal and thalamic deep brain stimulation in myoclonus dystonia
Authors: Krause Patricia , Koch Kristin , Gruber Doreen , Kupsch Andreas , Gharabaghi Alireza , Schneider Gerd‐Helge , Kühn Andrea A.
Published: January 2021

Objective

Observational study to evaluate long‐term effects of deep brain stimulation (DBS) of the globus pallidus internus (GPi) and the ventral intermediate thalamic nucleus (VIM) on patients with medically refractory myoclonus dystonia (MD).

Background

More recently, pallidal as well as thalamic DBS have been applied successfully in MD but long‐term data are sparse.

Methods

We retrospectively analyzed a cohort of seven MD patients with either separate (n = 1, VIM) or combined GPi‐ DBS and VIM‐DBS (n = 6). Myoclonus, dystonia and disability were rated at baseline (BL), short‐term (ST‐FU) and long‐term follow‐up (LT‐FU) using the United Myoclonus Rating Scale, Burke−Fahn−Marsden Dystonia Rating Scale (BFMDRS) and Tsui rating scale, respectively. Quality of life (QoL) and mood were evaluated using the SF‐36 and Beck Depression Inventory questionnaires, respectively.

Results

Patients reached a significant reduction of myoclonus at ST‐FU (62% ± 7.3%; mean ± SE) and LT‐FU (68% ± 3.4%). While overall motor BFMDRS changes were not significant at LT‐FU, patients with GPi‐DBS alone responded better and predominant cervical dystonia ameliorated significantly up to 54% ± 9.7% at long‐term. Mean disability scores significantly improved by 44% ± 11.4% at ST‐FU and 58% ± 14.8% at LT‐FU. Mood and QoL remained unchanged between 5 and up to 20 years postoperatively. No serious long‐lasting stimulation‐related adverse events were observed.

Conclusions

We present a cohort of MD patients with very long follow‐up of pallidal and/or thalamic DBS that supports the GPi as the favourable stimulation target in MD with safe and sustaining effects on motor symptoms (myoclonus>dystonia) and disability.
Complex effects of eslicarbazepine on inhibitory micro networks in chronic experimental epilepsy
Authors: Schmidt Sarah , Pothmann Leonie , Müller‐Komorowska Daniel , Opitz Thoralf , Soares da Silva Patrício , Beck Heinz
Published: January 2021

Objective

Many antiseizure drugs (ASDs) act on voltage‐dependent sodium channels, and the molecular basis of these effects is well established. In contrast, how ASDs act on the level of neuronal networks is much less understood.

Methods

In the present study, we determined the effects of eslicarbazepine (S‐Lic) on different types of inhibitory neurons, as well as inhibitory motifs. Experiments were performed in hippocampal slices from both sham‐control and chronically epileptic pilocarpine‐treated rats.

Results

We found that S‐Lic causes an unexpected reduction of feed‐forward inhibition in the CA1 region at high concentrations (300 µM), but not at lower concentrations (100 µM). Concurrently, 300 but not 100 μM S‐Lic significantly reduced maximal firing rates in putative feed‐forward interneurons located in the CA1 stratum radiatum of sham‐control and epileptic animals. In contrast, feedback inhibition was not inhibited by S‐Lic. Instead, application of S‐Lic, in contrast to previous data for other drugs like carbamazepine (CBZ), resulted in a lasting potentiation of feedback inhibitory post‐synaptic currents (IPSCs) only in epileptic and not in sham‐control animals, which persisted after washout of S‐Lic. We hypothesized that this plasticity of inhibition might rely on anti‐Hebbian potentiation of excitatory feedback inputs onto oriens‐lacunosum moleculare (OLM) interneurons, which is dependent on Ca2+‐permeable α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptors. Indeed, we show that blocking Ca2+‐permeable AMPA receptors completely prevents upmodulation of feedback inhibition.

Significance

These results suggest that S‐Lic affects inhibitory circuits in the CA1 hippocampal region in unexpected ways. In addition, ASD actions may not be sufficiently explained by acute effects on their target channels, rather, it may be necessary to take plasticity of inhibitory circuits into account.
Pyrolysis temperature and feedstock alter the functional groups and carbon sequestration potential of Phragmites australis‐ and Spartina alterniflora‐derived biochars
Authors: Wang Wei , Bai Junhong , Lu Qiongqiong , Zhang Guangliang , Wang Dawei , Jia Jia , Guan Yanan , Yu Lu
Published: January 2021

Biochar produced by pyrolysis of biomass under oxygen‐limited conditions has recently attracted increasing attention. To investigate the effects of feedstock and pyrolysis temperature on biochar characteristics, Phragmites australis straw and Spartina alterniflora straw were used to produce biochars at different temperatures from 300 to 500°C with an increment of 50°C. The biochars were characterized by their yields, ash contents, elemental compositions (i.e., carbon [C], hydrogen [H], oxygen [O], and nitrogen [N]), functional groups, dissolved organic carbon (DOC) contents, carbon sequestration potential, higher heating values (HHVs), and production costs. The results illustrated that pyrolysis temperature negatively affected biochar yields, H and O contents. In contrast, biochar produced at high temperature showed high ash contents, C contents, HHVs, and stronger aromaticity with low H/C and O/C ratios. In addition, S. alterniflora‐derived biochar (SB) contained higher ash content but lower C/H/N/O contents and HHVs than P. australis‐derived biochar (PB; p < 0.05). In addition, DOC contents in both SB and PB declined as temperature increased, and SB exhibited higher DOC contents than PB. Fourier transform infrared spectroscopy showed that absorption intensities of –OH, C=O, –CH, and –C–O–C‐stretching vibration declined with increasing temperature. The stability of the biochars was enhanced at high temperatures, and the biochar derived from S. alterniflora at 500°C might have a better carbon sequestration potential according to thermogravimetric analysis. Additionally, cost analysis showed that the production cost of biochar with large‐scale reactor was lower than that with bench‐scale reactor, and SB had a higher cost than PB due to the price of feedstock and drying process for the former. Our results could offer effective information on resource utilization of P. australis and S. alterniflora straw and are valuable for optimizing pyrolysis temperature to tune P. australis and S. alterniflora biochar properties for specific environmental usage.
Evolutionary time best explains the latitudinal diversity gradient of living freshwater fish diversity
Authors: Miller Elizabeth Christina , Román‐Palacios Cristian
Published: January 2021

Aim

The evolutionary causes of the latitudinal diversity gradient are debated. Hypotheses have ultimately invoked either faster rates of diversification in the tropics or more time for diversification owing to the tropical origins of higher taxa. Here, we perform the first test of the diversification rate and time hypotheses in freshwater ray‐finned fishes, a group comprising nearly a quarter of all living vertebrates.

Location

Global.

Time period

368–0 Ma.

Major taxa studied

Extant freshwater ray‐finned fishes.

Methods

Using a mega‐phylogeny of actinopterygian fishes and a global database of occurrence records, we estimated net diversification rates, the number of colonizations and regional colonization times of co‐occurring species in freshwater drainage basins. We used generalized additive models to test whether these factors were related to latitude. We then compared the influence of diversification rates, numbers of colonizations, colonization times and surface area on species richness, and how these factors are related to each other.

Results

Although both diversification rates and time were related to richness, time had greater explanatory power and was more strongly related to latitude than diversification rates. Other factors (basin surface area and number of colonizations) also helped to explain richness but were unrelated to latitude. The most diverse freshwater basins of the world (Amazon and Congo rivers) were dominated by lineages having Mesozoic origins. The temperate groups dominant today arrived near the Cretaceous–Palaeogene boundary, leaving comparatively less time to build richness. Diversification rates and colonization times were inversely related: recently colonized basins had the fastest rates, whereas ancient species‐rich faunas had slower rates.

Main conclusions

We concluded that time is the leading driver of latitudinal disparities in richness in freshwater fish faunas. We suggest that the most likely path to building very high species richness is through diversification over long periods of time, rather than through rapid diversification.