bluuebunny/crossref_metadata_2025 huggingface dataset:
Age-associated changes in endothelial transcriptome and chromatin landscape correlate with elevated risk of hemorrhage
Authors: Mohan Kshitij , Gasparoni Gilles , Salhab Abdulrahman , Orlich Michael M. , Geffers Robert , Hoffmann Steve , Adams Ralf H. , Walter Jörn , Nordheim Alfred
Published: February 2023

Intracerebral hemorrhage (ICH), a devastating form of stroke, is a leading global cause of human death and disability. The major risk factors for ICH include increasing age, hypertension and cerebral amyloid angiopathy. Despite high mortality and morbidity associated with ICH, the mechanisms leading to blood-brain barrier (BBB) dysfunction with age and development of hemorrhagic stroke is poorly understood. In the vasculature of the central nervous system, endothelial cells (ECs) constitute the core component of the BBB and provide a physical barrier due to tight junctions, adherens junctions, and basement membrane layers. In this study, we show in brains of mice that incidents of intracerebral bleeding increase with advancing age. After isolation of an enriched population of cerebral ECs, we studied gene expression in ECs isolated from murine brains of increasing ages of 2, 6, 12, 18, and 24 months. The study reveals agedependent dysregulation of 1388 genes in the ECs, including many involved in the maintenance of BBB and vascular integrity. Since epigenetic mechanisms regulate gene expression, we also investigated age-dependent changes at the levels of CpG methylation and accessible chromatin in cerebral ECs. Our study reveals correlations between age-dependent changes in chromatin structure and gene expression. We find significant age-dependent downregulation of the apelin receptor (Aplnr) gene along with an age-dependent reduction in chromatin accessibility of the promoter of this gene.Aplnris known to play a crucial role in positive regulation of vasodilation and is implicated in vascular health. Interestingly, we also observe an age-dependent reduction in the protein expression levels of the apelin receptor in the brain, potentially implicating the apelin receptor to be critical for the increased risk of intracerebral hemorrhage with ageing.
Effect of the SARS-CoV-2 Delta-associated G15U mutation on the s2m element dimerization and its interactions with miR-1307-3p
Authors: Cunningham Caylee L. , Frye Caleb J. , Makowski Joseph A. , Kensinger Adam H. , Shine Morgan , Milback Ella J. , Lackey Patrick E. , Evanseck Jeffrey D. , Mihailescu Mihaela-Rita
Published: February 2023

The stem loop 2 motif (s2m), a highly conserved 41-nucleotide hairpin structure in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome, serves as an attractive therapeutic target that may have important roles in the virus life cycle or interactions with the host. However, the conserved s2m in Delta SARS-CoV-2, a previously dominant variant characterized by high infectivity and disease severity, has received relatively less attention than that of the original SARS-CoV-2 virus. The focus of this work is to identify and define the s2m changes between Delta and SARS-CoV-2 and subsequent impact of those changes upon the s2m dimerization and interactions with the host microRNA miR-1307-3p. Bioinformatics analysis of the GISAID database targeting the s2m element reveals a greater than 99% correlation of a single nucleotide mutation at the 15thposition (G15U) in Delta SARS-CoV-2. Based on1H NMR assignments comparing the imino proton resonance region of s2m and the G15U at 19°C, we find that the U15-A29 base pair closes resulting in a stabilization of the upper stem without overall secondary structure deviation. Increased stability of the upper stem did not affect the chaperone activity of the viral N protein, as it was still able to convert the kissing dimers formed by s2m G15U into a stable duplex conformation, consistent with the s2m reference. However, we find that the s2m G15U mutation drastically reduces the binding affinity of the host miR-1307-3p. These findings demonstrate that the observed G15U mutation alters the secondary structure of s2m with subsequent impact on viral binding of host miR-1307-3p, with potential consequences on the immune response.
RNA polymerase sliding on DNA can couple the transcription of nearby bacterial operons
Authors: Tenenbaum Debora , Inlow Koe , Friedman Larry , Cai Anthony , Gelles Jeff , Kondev Jane
Published: February 2023

DNA transcription initiates after an RNA polymerase (RNAP) molecule binds to the promoter of a gene. In bacteria, the canonical picture is that RNAP comes from the cytoplasmic pool of freely diffusing RNAP molecules. Recent experiments suggest the possible existence of a separate pool of polymerases, competent for initiation, which freely slide on the DNA after having terminated one round of transcription. Promoter-dependent transcription reinitiation from this pool of post-termination RNAP may lead to coupled initiation at nearby operons, but it is unclear whether this can occur over the distance- and time-scales needed for it to function widely on a bacterial genome in vivo. Here, we mathematically model the hypothesized reinitiation mechanism as a diffusion-to-capture process and compute the distances over which significant inter-operon coupling can occur and the time required. These quantities depend on previously uncharacterized molecular association and dissociation rate constants between DNA, RNAP and the transcription initiation factorσ70; we measure these rate constants using single-molecule experiments in vitro. Our combined theory/experimental results demonstrate that efficient coupling can occur at physiologically relevantσ70concentrations and on timescales appropriate for transcript synthesis. Coupling is efficient over terminator-promoter distances up to ∼ 1, 000 bp, which includes the majority of terminator-promoter nearest neighbor pairs in theE. coligenome. The results suggest a generalized mechanism that couples the transcription of nearby operons and breaks the paradigm that each binding of RNAP to DNA can produce at most one messenger RNA.

SIGNIFICANCE STATEMENT

After transcribing an operon, a bacterial RNA polymerase can stay bound to DNA, slide along it, and reini-tiate transcription of the same or a different operon. Quantitative single-molecule biophysics experiments combined with mathematical theory demonstrate that this reinitiation process can be quick and efficient over gene spacings typical of a bacterial genome. Reinitiation may provide a mechanism to orchestrate the transcriptional activities of groups of nearby operons.
Circular mitochondrial-encoded mRNAs are a distinct subpopulation of mitochondrial mRNA inTrypanosoma brucei
Authors: Smoniewski Clara M. , Borujeni Poorya Mirzavand , Petersen Austin , Hampton Marshall , Salavati Reza , Zimmer Sara L.
Published: February 2023

Since the first identification of circular RNA (circRNA) in viral-like systems, reports of circRNAs and their functions in various organisms, cell types, and organelles have greatly expanded. Here, we report the first evidence of circular mRNA in the mitochondrion of the eukaryotic parasite,Trypanosoma brucei. While using a circular RT-PCR technique developed to sequence mRNA tails of mitochondrial transcripts, we found that some mRNAs are circularized without anin vitrocircularization step normally required to produce PCR products. Starting from totalin vitrocircularized RNA andin vivocircRNA, we high-throughput sequenced three transcripts from the 3’ end of the coding region, through the 3’ tail, to the 5’ start of the coding region. We found that fewer reads in the circRNA libraries contained tails than in the total RNA libraries. When tails were present on circRNAs, they were shorter and less adenine-rich than the total population of RNA tails of the same transcript. Additionally, using hidden Markov modelling we determined that enzymatic activity during tail addition is different for circRNAs than for total RNA. Lastly, circRNA UTRs tended to be shorter and more variable than those of the same transcript sequenced from total RNA. We propose a revised model of Trypanosome mitochondrial tail addition, in which a fraction of mRNAs is circularized prior to the addition of adenine-rich tails and may act as a new regulatory molecule or in a degradation pathway.
Fluctuations and entropy enable neural crest cell ingression
Authors: Pasiliao Clarissa C. , Thomas Evan C. , Yung Theodora , Zhu Min , Tao Hirotaka , Sun Yu , Goyal Sidhartha , Hopyan Sevan
Published: February 2023

The second law of thermodynamics explains the dissipative nature of embryonic development as an exchange of energy-dependent order for proportionately greater output of heat and waste. Recent work on granular matter provides a path by which to define the roles of passive, stochastic mechanisms in nonequilibrium systems. Here, we apply such a framework to examine the role of thermodynamic parameters to cell ingression, the movement of cells from one tissue layer to another that has been attributed, in part, to directional cues. Using the murine neural crest as a model system, we provide evidence that a stochastic mechanism, rather than a proposed stiffness gradient, underlies cell ingression. Cortical fluctuations representing effective temperature and cell packing configurations generate an entropic trap that promotes cell ingression. The results imply dissipative mechanisms that transiently disorder tissue underlie some morphogenetic events.
Rationally designed protein bandpass filters for controlling cellular signaling with chemical inputs
Authors: Shui Sailan , Scheller Leo , Correia Bruno E.
Published: February 2023

Biological mechanisms that rely on signal integration and processing are fundamental for cell function. These types of capabilities are analogous to those found in electronic circuits where individual components perform operations on input signals. In electronics, bandpass filters are crucial components to narrow frequencies within a specified range and reject frequencies outside of that range. However, no generalizable protein-based components are currently available to mimic such processes in engineered biological systems, representing an unmet need in controllable modules. Here, we propose a rational design approach to create protein-basedchemically responsive bandpass filters(CBP) which pass chemical concentrations within a range and reject concentrations outside of that range, showing an OFF-ON-OFF regulatory pattern. The CBPs were designed using structure-based approaches where we created a heterodimeric construct which the assembly is triggered by low concentration of a small-molecule, and this interaction is inhibited at high concentrations of the drug, effectively creating a bandpass filter. The CBPs have a multidomain architecture where we used known drug-receptors, a computationally designed protein binder and small-molecule inhibitors. Owing to the modularity of the system, each domain of the CBPs can be rationally fine-tuned to optimize its performance, including bandwidth, maximum response, cutoff concentration and fold changes. These CBPs were used to regulate cell surface receptor signaling pathways showing the capability to control cellular activities in engineered cells.
Development of an instrument to assess independent online learning readiness of high school students in Indonesia
Authors: Belawati Tian , Daryono Daryono , Sugilar Sugilar , Kusmawan Udan
Published: February 2023

Purpose

The paper reports a study that was intended to develop a self-assessment instrument to measure high school students' readiness for pursuing independent online learning.

Design/methodology/approach

The instrument was developed through the following steps: (1) developing the draft, (2) checking the instrument's face validity and (3) testing the instrument's validity, reliability and discriminant capacity using PLS analysis.

Findings

The study has developed a tool to self-assess high school students' readiness for independent online learning. The instrument consists of 36 statement items and is statistically proven to have good reliability, construct and indicator validity and a discriminating power.

Research limitations/implications

The instrument items were designed to fit the context of Indonesian high school students. However, only responses from high school students in rather urban areas were used to test the validity and reliability of the instrument. This could imply that the instrument is only accurate in urban settings.

Practical implications

As a result of the research, a tool to assess high school students' readiness for independent online learning has been created. To better prepare students for independent online learning endeavors, the school might use the results to enhance areas that need improvement.

Originality/value

The study succeeded in developing a contextualized self-assessment tool for measuring Indonesian students' independent online learning readiness.
The impact of audit data analytics on audit quality and audit review continuity in Thailand
Authors: Ditkaew Kanthana , Suttipun Muttanachai
Published: February 2023

Purpose

The main objective of this study is to examine the impact of audit data analytics (ADA) on audit quality (AQ) and audit review continuity (ARC).

Design/methodology/approach

Using 452 CPAs in Thailand as samples, mail questionnaires were used and sent to collect the data. Descriptive analysis, correlation matrix and path analysis were used to analyze the data.

Findings

The results of this study indicated that audit data analytics had a positive impact on AQ and ARC. Cybersecurity, used as a moderator in this study, was found to be the interaction between ADA, AQ and review continuity.

Practical implications

Auditors and audit firms can consider using big data in their data analytics to improve AQ and ARC.

Originality/value

Resource advantage theory has been used in this study to explain the impact of ADA on AQ and ARC in Thailand.
Dealcoholised wine: exploring the purchasing considerations of South African Generation Y consumers
Authors: Filter Markus , Pentz Chris D.
Published: February 2023

Purpose

This study contributes to the scant research on dealcoholised wine from a consumer behaviour perspective by providing insight and reporting on the attributes that South African Generation Y consumers prefer when purchasing dealcoholised wine.

Design/methodology/approach

A two-phased research approach was adopted, involving a main quantitative phase, preceded by a qualitative phase. Data were gathered from 626 South African Generation Y respondents by means of a questionnaire. The best–worst scaling method was applied to 13 selected dealcoholised wine attributes, to measure the level of importance of each attribute. To gain more insight on the data, the best-worst scaling scores were further standardised to a probabilistic ratio scale.

Findings

“Taste”, “price” and “I have tried it before” were the most important attributes that respondents considered when purchasing dealcoholised wine. Furthermore, “taste” was by far the most important of all the attributes. The attributes of “back label”, “attractive front label” and “brand name” were identified as the least important by the respondents, suggesting that they did not consider the visual elements of a bottle of dealcoholised wine as particularly important in their purchasing decision.

Originality/value

The findings of this pioneering study contribute to the lack of knowledge about dealcoholised wine from a consumer behaviour and marketing perspective, and provide insights and strategies that can be used by stakeholders to enhance the dealcoholised wine market in South Africa.
The effects of government spending on consumption and the real exchange rate: a comparison between developed and developing countries
Authors: Li Yu , Zhu Xiaoyang
Published: February 2023

Purpose

The degree of development and the way to identify a fiscal shock matter in evaluating the effects of the fiscal policy. This paper contributes to the debate on the effects of a fiscal expansion on private consumption and the real effective exchange rate.

Design/methodology/approach

This paper uses a sign-restriction method to identify a fiscal shock in the panel structural VAR analysis in the context of both developed and developing countries.

Findings

The authors’ find that (1) private consumption increases in response to a positive government spending shock in both groups, yet such consumption effect is greater in developing than industrial countries; (2) the response of real effective exchange rate to the government spending shock varies across groups: it depreciates in developed countries and appreciates in developing countries; (3) trade balance improves in both groups.

Originality/value

This study sheds light on the differential effects of fiscal shock on consumption and real exchange rate in both developed and developing economies.
The late payment epidemic in UK construction
Authors: Stewardson Alice , Edwards David J. , Asamoah Eric , Aigbavboa Clinton Ohis , Lai Joseph H.K. , El-Gohary Hatem
Published: February 2023

Purpose

The UK government has elaborated the effect of late payment on the economy, with its impact on the construction sector being particularly pronounced. This paper aims to evaluate the late payment epidemic that persists within the construction industry, specifically analysing the effectiveness of government-led voluntary payment initiatives.

Design/methodology/approach

A mixed philosophical lens is adopted that incorporates both pragmatism and post-positivism to examine the late payment phenomena. Couched within deductive reasoning and a case study strategy, a questionnaire survey was conducted to elicit responses from one-hundred construction professionals. Elucidating upon respondents’ perceptions of the UK’s late payment epidemic, a comparative analysis was undertaken of upstream (main contractor) and downstream (subcontractors/suppliers) contractors through Cronbach’s alpha, descriptive statistics, independence chi-square test, Kruskal–Wallis test and Mann–Whitney U test.

Findings

Emergent findings reveal that in practice, the monitoring and enforcement of government-led voluntary payment initiatives has been unprosperous with numerous contractors being forced to adopt indefensibly poor and punitive payment practices. Survey responses and extant literature substantiate and underscore the industry’s need to strengthen voluntary government-led payment initiatives. To create a responsible payment culture, any future code created should be mandatory and enforceable as a self-regulating approach has failed dismally. The work concludes with practical additional measures that could be introduced to create a responsible payment culture and promote ethical trading within the UK construction industry.

Originality/value

This paper constitutes a novel vignette of, and reflection upon, contemporary practice in this area of construction finance and serves to emphasise that very little has changes in the sector despite numerous UK government led reports and interventions.
Co-creating value and well-being experiences in physiotherapy services
Authors: Chwialkowska Agnieszka , Bhatti Waheed Akbar , Arslan Ahmad , Glowik Mario
Published: February 2023

Purpose

The purpose of this paper is to study the US-based (American) physiotherapy customers’ goals to engage in value cocreation activities during their well-being experience.

Design/methodology/approach

The authors perform Smart PLS-SEM analysis of the primary data of physiotherapy service customers in the USA.

Findings

The findings show that the US well-being customer engages in physiotherapy for individualizing, empowering, development, concerted and ethical motives but not for relating motives. These findings are contrasted with previous research to show that the service-dominant logic is not sufficient to account for the contextual complexity of the well-being experience and to explain the identified differences across culturally different customer segments.

Research limitations/implications

By integrating insights from health-care and cross-cultural literature, the authors highlight the importance of relationship dynamics, culture and institutional context in well-being sector and develop a more comprehensive understanding of the cocreation behaviors in this industry. This helps advance the value cocreation research in well-being sector and promote the well-being experiences such as physiotherapy.

Originality/value

The authors draw from a variety of disciplinary perspectives and challenge the service-dominant (S-D) logic as insufficient in explaining the value cocreation between the customer and expert in the well-being sector. The authors adapt physician–patient relationship model from health-care literature and cultural values of power distance from cross-cultural literature to complement the S-D logic to account for the complexity and nuanced context of the well-being cocreation experience.
Obese destinations
Authors: Pektaş Fatih
Published: February 2023

Purpose

Whether a human body has a healthy carrying capacity is calculated by body mass index (BMI). The BMI is found by dividing body weight in kilograms by the square of body length. If the person's body weight is more than the heaviness that the body can carry healthily, it is called obesity. Destinations have a specific area, just like a human body. Therefore, any destination whose carrying capacity is exceeded can be called an “obese destination”. This study's primary purpose is to reveal the importance of destination carrying capacity through the concept of obesity.

Design/methodology/approach

Content analysis, one of the qualitative research methods, was employed, and graffiti reflecting the feelings of the local people toward tourists were used as data. Graffiti was considered as a social carrying capacity indicator to identify obese destination symptoms. Fifty graffiti obtained from search engines about destinations with obesity problems were analyzed.

Findings

The study's findings reveal that anti-tourist graffiti indicates obese destination symptoms. Furthermore, when the content analysis of graffiti is examined, it is seen that the obese destination's local people have intense anger toward tourists. This is a clear manifestation of the destination's health deterioration.

Originality/value

This study, in which the concept of obese destination is used for the first time, suggests that destinations' health may worsen just like people. If destinations with over-tourism are called obese, a more expansive awareness will be created about the destinations' problems. The study suggests that nonecolabel can be used as a mandatory diet tool for obese destinations. Anti-tourist graffiti has been addressed as an obese destination symptom.
Are the motives of holding cash differing between developed and emerging financial markets?
Authors: Akhtar Tahir
Published: February 2023

Purpose

This study compares the motives of holding cash between developed (Australian) and developing (Malaysian) financial markets.

Design/methodology/approach

For the period 2006–2020, the t-test, fixed-effect and generalised method of moment (GMM) model have been applied to a sample of 1878 (1,165 Australian and 713 Malaysian) firms.

Findings

The empirical results reveal that firms in developed financial markets hold higher cash compared to the developing financial markets. The findings confirm that motives to hold cash differ between developed and developing financial markets. The GMM findings further show that cash holdings (CH) in Australia are higher due to higher ratios of cash flow, research and development (R&D) and return on assets (ROA), and lower due to larger dividend payments. In the Malaysian market, however, cash flows and R&D are ineffectual, ROA falls and dividend payments rise CH.

Practical implications

The study helps managers, practitioners and investors understand that firms' distinct economic, institutional, accounting and financial environments are important. To attain the desired outcomes, they must thus comprehend and consider these considerations while developing suitable liquidity strategies.

Originality/value

To the authors' best knowledge, this is the initial research demonstrating how varied cash motives and their ramifications are in developed and developing financial markets. Therefore, this study identifies the importance that CH motives varied among financial markets and that findings from a particular market cannot be generalised to other markets because of the market and financial structural variations.
Do clients’ environmental risks affect audit pricing? Evidence from environmental violations in China
Authors: Yao Sheng , Wei Siyu , Chen Lining
Published: February 2023

Purpose

Existing studies have shown that all kinds of audit risks greatly affect audit pricing for accounting firms. However, it is still unclear whether environmental risks caused by environmental violations lead to a high audit fee. This study aims to investigate whether accounting firms raise audit fees after client firms have violated environmental regulations or have been punished for such violations.

Design/methodology/approach

This study selects listed firms with environmental violations between 1994 and 2018 as the treatment sample and match the treatment group with a control group of firms from the same industry, of similar asset size and with no environmental violations for the same time period. Then, this study constructs a difference-in-difference (DID) model to explore the impact of firm environmental violations (or punishment for environmental violations) on the audit pricing.

Findings

This study finds that accounting firms tend to raise audit fees after client firms have violated environmental regulations or have been punished for such violations, and this increasing effect is different due to environmental regulation intensity, regional span and internal control defects. Further evidences show that environmental violations influence audit fees through financial restatement, whereas environmental punishments impact audit fees through earnings management and risk-taking.

Originality/value

This study enriches the literature on determining factors of audit fees and economic consequences of environmental violations and provides empirical supports to understand the pricing behavior of accounting firms.
uBin: A manual refining tool for genomes from metagenomes
Authors: Bornemann Till L. V. , Esser Sarah P. , Stach Tom L. , Burg Tim , Probst Alexander J.
Published: February 2023

Resolving bacterial and archaeal genomes from metagenomes has revolutionized our understanding of Earth's biomes yet producing high‐quality genomes from assembled fragments has been an ever‐standing problem. While automated binning software and their combination produce prokaryotic bins in high throughput, their manual refinement has been slow, sometimes difficult or missing entirely facilitating error propagation in public databases. Here, we present uBin, a GUI‐based, standalone bin refiner that runs on all major operating platforms and was additionally designed for educational purposes. When applied to the public CAMI dataset, refinement of bins using GC content, coverage and taxonomy was able to improve 78.9% of bins by decreasing their contamination. We also applied the bin refiner as a standalone binner to public metagenomes from the International Space Station and demonstrate the recovery of near‐complete genomes, whose replication indices indicate the active proliferation of microbes in Earth's lower orbit. uBin is an easy to instal software for bin refinement, binning of simple metagenomes and communication of metagenomic results to other scientists and in classrooms. The software and its helper scripts are open source and available under https://github.com/ProbstLab/uBin.
Bacterial genome sequencing tracks the housefly‐associated dispersal of fluoroquinolone‐ and cephalosporin‐resistant Escherichia coli from a pig farm
Authors: Behrens Wiebke , Kolte Baban , Junker Vera , Frentrup Martinique , Dolsdorf Claudia , Börger Maria , Jaleta Megarsa , Kabelitz Tina , Amon Thomas , Werner Doreen , Nübel Ulrich
Published: February 2023

The regular use of antimicrobials in livestock production selects for antimicrobial resistance. The potential impact of this practice on human health needs to be studied in more detail, including the role of the environment for the persistence and transmission of antimicrobial‐resistant bacteria. During an investigation of a pig farm and its surroundings in Brandenburg, Germany, we detected abundant cephalosporin‐ and fluoroquinolone‐resistant Escherichia coli in pig faeces, sedimented dust, and house flies (Musca domestica). Genome sequencing of E. coli isolates revealed large phylogenetic diversity and plasmid‐borne extended‐spectrum beta lactamase (ESBL) genes CTX‐M‐1 in multiple strains. [Correction added on 28 February 2023, after first online publication: In the preceding sentence, ‘and TEM‐1’ was previously included but has been deleted in this version.] Close genomic relationships indicated frequent transmission of antimicrobial‐resistant E. coli between pigs from different herds and across buildings of the farm and suggested dust and flies as vectors for dissemination of faecal pathogens. Strikingly, we repeatedly recovered E. coli from flies collected up to 2 km away from the source, whose genome sequences were identical or closely related to those from pig faeces isolates, indicating the fly‐associated transport of diverse ESBL‐producing E. coli from the pig farm into urban habitation areas. The observed proximity of contaminated flies to human households poses a risk of transmission of antimicrobial‐resistant enteric pathogens from livestock to man.
Empirical evidence on the global minimum tax: what is a critical mass and how large is the substance‐based income exclusion?
Authors: Devereux Michael P. , Paraknewitz Johanna , Simmler Martin
Published: February 2023

This paper presents empirical evidence on the proposed global minimum tax (GMT) of the OECD's Pillar 2. First, it addresses how many, and which, countries or country groups can be seen as constituting a ‘critical mass’ for its successful implementation; given such a critical mass, remaining jurisdictions worldwide will have an incentive to implement the GMT as well. Second, it assesses the generosity of the substance‐based income exclusion (SBIE), which is informative for the revenue collected under the GMT.
From fork to farm: Impacts of more sustainable diets in the EU‐27 on the agricultural sector
Authors: Rieger Jörg , Freund Florian , Offermann Frank , Geibel Inna , Gocht Alexander
Published: February 2023

The implications of dietary changes for the environment and for human health are well documented, but the impacts on the agricultural sector are less well researched. We fill this gap by specifying scenarios in which European consumers' diets approximate the EAT‐Lancet dietary recommendations to varying degrees and estimate the effects on agricultural production, incomes and emissions using an agro‐economic modelling framework. The combination of different models allows for a detailed assessment of consequences for the agricultural sector from the global through European NUTS2 level to the farm level at different time scales. Shifting European consumption towards the EAT‐Lancet recommendations leads to decreasing production of animal‐based products, while production of fruits and vegetables increases sharply. The results indicate that the agricultural sector could benefit from a dietary shift, though the results are mixed at country, regional and farm levels. In particular, countries and regions that are highly specialised in animal farming are likely to lose income—at least in the short run—while regions with higher shares of vegetable and fruit farms can expect income gains. In Germany, pig and poultry farms may experience losses of up to 34% of their income, whereas farms with a high share of vegetables could gain more than 30% in income. Our results have implications for the policies to assist these extensive structural adjustments in response to widespread dietary changes.
Dragon unbound? Regional influences on China's policies in the Middle East—Introduction
Authors: Fardella Enrico , Friedman Brandon
Published: February 2023

China has manifested its aspiration to create an interdependent global network that integrates its commercial, strategic, political, and cultural connections across the world. Eurasia, and the Middle East and North Africa within it, have certainly become a core part of China's global design. This volume aims to explain the process of Chinese expansion in the Middle East from an ‘inside‐out’ perspective. It includes a series of country‐specific case studies aimed at evaluating how local actors and their agencies have shaped China's role in the region.
Functional and cognitive rehabilitation interventions during intensive care admission: A protocol for a systematic integrative review
Authors: Collet Marie Oxenbøll , Laerkner Eva , Jensen Janet , Egerod Ingrid , Christensen Jan , Jørgensen Niels Kasper , Kjærgaard Rikke Schmidt , Olausson Sepideh , Wøien Hilde , Lange Theis , Nielsen Anne Højager , Kjær Maj‐Brit Nørregaard , Bruun Camille Rahbek Lysholm , Perner Anders
Published: February 2023

Background

Long‐term cognitive impairment occurs in up to 60% of intensive care unit (ICU) survivors. Early use of functional and cognitive rehabilitation interventions, while patients are still in ICU, may reduce cognitive decline. We aim to describe the functional and cognitive interventions used during the ICU stay, the healthcare professionals providing interventions, and the potential impact on functional and cognitive rehabilitation.

Method

In this integrative systematic review, we will include empirical qualitative, quantitative, mixed‐ and multiple‐methods studies assessing the use of functional and cognitive rehabilitation provided in ICU. We will identify studies in relevant electronic databases from 2012 to 2022, which will be screened for eligibility by at least two reviewers. Literature reported as narrative reviews and editorials will be excluded. We will assess the impact of interventions evaluating a cognitive and functional function, quality of life, and all‐cause mortality at 6–12 months after ICU discharge. The Revised Cochrane risk‐of‐bias Tool will be used for assessing risk of bias in clinical trials. For observational studies, we will use the National Institutes of Health Quality Assessment tool for Observational Cohort and Cross‐Sectional Studies. Furthermore, we will use the critical appraisal skills programme for qualitative studies and the mixed methods appraisal tool for mixed methods studies. We will construct four matrices, including results describing which ICU patients and healthcare professionals were engaged in rehabilitation, which interventions were included in early rehabilitation in ICU, the potential impact on patient outcomes of rehabilitation interventions provided in ICU and a narrative synthesis of themes. A summary of the main results will be reported using modified GRADE methodology.

Impact

This integrative review will inform the feasibility randomised clinical trial testing the development of a complex intervention targeting functional and cognitive rehabilitation for patients in ICU.
Is clinicians' alcohol consumption associated with their preventive practices to reduce unhealthy alcohol use? A systematic review of current evidence
Authors: Romero‐Rodríguez Esperanza , Fuster Daniel , Pérula de Torres Luis Ángel , Saitz Richard
Published: February 2023

Clinicians' risk behaviors, including their personal alcohol use, may influence patients' attitudes and motivation to make changes in their lifestyle, as well as the provision of clinical preventive services to reduce unhealthy behaviors. The aim of the systematic review was to summarize the existing evidence on the association between clinicians' alcohol consumption and their preventive practices to reduce unhealthy alcohol use. The review was conducted following Cochrane guidelines and Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) statement guidance. Three databases (Cochrane, MEDLINE, Web of Science) were queried from July 1, 2021, through November 30, 2021. We included quantitative observational studies reporting clinicians' alcohol use associations with relevant preventive practices. Two reviewers independently screened articles for inclusion, extracted data, and assessed the quality of selected studies. Ten studies, published from 1986 to 2018, were included. We found a statistically significant association between clinicians' alcohol consumption and their preventive practices to reduce unhealthy alcohol use in eight of the 10 studies. Clinicians who drank larger quantities of alcohol offered less screening and counseling to their patients about alcohol use. Clinicians who drank regularly (3 days a week or more) were less likely to screen for alcohol use, and the frequency of alcohol use by those professionals was inversely related to recommending quitting. Clinicians' alcohol use appears to be associated with their screening for unhealthy alcohol use and counseling to reduce it. The frequency and quantity of clinicians' alcohol consumption were also associated with their practices to address unhealthy alcohol use.
Understanding perceived addiction to and addictiveness of electronic cigarettes among electronic cigarette users: a cross‐sectional analysis of the International Tobacco Control Smoking and Vaping (ITC 4CV) England Survey
Authors: Lohner Valerie , McNeill Ann , Schneider Sven , Vollstädt‐Klein Sabine , Andreas Marike , Szafran Daria , Grundinger Nadja , Demjén Tibor , Fernandez Esteve , Przewozniak Krzysztof , Tountas Yannis , Trofor Antigona , Zatonski Witold , Willemsen Marc C. , Vardavas Constantine , Fong Geoffrey T. , Mons Ute
Published: February 2023

Background and Aims

The addictive potential of electronic cigarettes (e‐cigarettes) remains to be fully understood. We identified patterns and correlates of perceived addiction to e‐cigarettes and perceived addictiveness of e‐cigarettes relative to tobacco cigarettes (relative addictiveness) in dual users as well as exclusive e‐cigarette users.

Design, Setting and Participants

Observational study using cross‐sectional survey data from England (2016) from the International Tobacco Control Project (ITC) Four Country Smoking and Vaping (4CV) survey. The study comprised 832 current e‐cigarette users who had been vaping for at least 4 months.

Measurements

Perceived addiction to e‐cigarettes and relative addictiveness of e‐cigarettes were examined. Socio‐demographic factors were age, gender and education; markers of addiction included urge to vape, time to first vape after waking and nicotine strength used; vaping and smoking characteristics included frequency and duration of e‐cigarette use, intention to quit, adjustable power or temperature, enjoyment, satisfaction relative to tobacco cigarettes and tobacco cigarette smoking status.

Findings

A total of 17% of participants reported feeling very addicted to e‐cigarettes, while 40% considered e‐cigarettes equally/more addictive than tobacco cigarettes. Those who felt very addicted had higher odds of regarding e‐cigarettes as more addictive than tobacco cigarettes (odds ratio 3.4, 95% confidence interval 2.3–5.1). All markers of addiction, daily use and enjoyment were associated with higher perceived addiction, whereas time to first vape after waking, daily vaping and perceiving vaping as less satisfying than smoking were associated with relative addictiveness.

Conclusions

Markers of addiction to e‐cigarettes appear to correspond with perceived addiction to e‐cigarettes, suggesting that self‐reported perceived addiction might serve as an indicator of addiction. Prevalence both of markers of addiction and perceived addiction were comparatively low overall, suggesting a limited but relevant addictive potential of e‐cigarettes. Additionally, positive and negative reinforcement, reflected here by enjoyment and relative satisfaction, might play a role in e‐cigarette addiction.
Oncologic outcomes in myxofibrosarcomas: the role of a multidisciplinary approach and surgical resection margins
Authors: Rhee Isaac , Spazzoli Benedetta , Stevens Jarrad , Hansa Annjaleen , Spelman Tim , Pang Grant , Guiney Michael , Powell Gerard , Choong Peter , Di Bella Claudia
Published: February 2023

Backgrounds

Myxofibrosarcomas (MFS) are malignant soft tissue sarcomas with an infiltrative growth pattern and propensity for local recurrence(LR).We aimed to assess our management of MFS and make recommendations about the role of a multidisciplinary team approach and margin widths.

Methods

Fifty‐seven patients were identified with MFS treated at a single sarcoma centre between 1998 and 2020. Patients were stratified based on whether they presented for a planned resection (59.6%) or after an unplanned resection (40.4%) performed at a non‐specialized facility. All patients underwent radiotherapy before definitive surgery.

Results

73.7% underwent a combined onco‐plastic approach. The 5 year LRFS rate was 78.2% (84.4%, planned, versus 70.1%, unplanned, P = 0.194) and found comparable oncological outcomes between the planned and unplanned groups for the 5 year metastasis free survival (74.5% versus 86.1%, P = 0.257), disease free survival (70.1% versus 72.4%, P = 0.677), and Overall Survival (64.5% versus 75.9%, P = 0.950). Margin width ≥ 2 cm was obtained in 84.2% of cases and improved local control (HR = 0.22; 95% CI 0.06–0.81; P = 0.023), metastasis (HR = 0.24; 95% CI 0.07–0.80; P = 0.019) and mortality rates (HR = 0.23; 95% CI 0.09, 0.61; P = 0.003) compared to <2 cm. Margin width > 3 cm did not further affect oncological outcomes.

Conclusion

Our study shows that a multidisciplinary team approach allows the achievement of low local recurrence rate and good oncological outcomes of myxofibrosarcomas, regardless of presentation status. We recommend a minimum of 2 cm margin width.
Activation of Kir4.1/Kir5.1 contributes to the cyclosporin A‐induced stimulation of the renal NaCl cotransporter and hyperkalemic hypertension
Authors: Gao Zhong‐Xiuzi , Zhou Rui , Li Ming‐Yan , Li Shu‐Ting , Mao Zi‐Hui , Shu Ting‐Ting , Liu Dong‐Wei , Liu Zhang‐Suo , Wu Peng
Published: February 2023

Aim

Cyclosporin A (CsA) is a widely used immunosuppressive drug that causes hypertension and hyperkalemia. Moreover, CsA‐induced stimulation of the thiazide‐sensitive NaCl cotransporter (NCC) in the kidney has been shown to be responsible for the development of hyperkalemic hypertension. In this study, we tested whether CsA induces the activation of NCC by stimulating the basolateral Kir4.1/Kir5.1 channel in the distal convoluted tubule (DCT).

Methods

Electrophysiology, immunoblotting, metabolic cages, and radio‐telemetry methods were used to examine the effects of CsA on Kir4.1/Kir5.1 activity in the DCT, NCC function, and blood pressure in wild‐type (WT) and kidney‐specific Kir4.1 knockout (KS‐Kir4.1 KO) mice.

Results

The single‐channel patch clamp experiment demonstrated that CsA stimulated the basolateral 40 pS K+ channel in the DCT. Whole‐cell recording showed that short‐term CsA administration (2 h) not only increased DCT K+ currents but also shifted the K+ current (IK) reversal potential to the negative range (hyperpolarization). Furthermore, CsA administration increased phosphorylated NCC (pNCC) levels and inhibited renal Na+ and K+ excretions in WT mice but not in KS‐Kir4.1 KO mice, suggesting that Kir4.1 is required to mediate CsA effects on NCC function. Finally, long‐term CsA infusion (14 days) increased blood pressure, plasma K+ concentration, and total NCC or pNCC abundance in WT mice, but these effects were blunted in KS‐Kir4.1 KO mice.

Conclusion

We conclude that CsA stimulates basolateral K+ channel activity in the DCT and that Kir4.1 is essential for CsA‐induced NCC activation and hyperkalemic hypertension.
Trophic ecology, microhabitat specificity and morphology of Gymnodactylus darwinii Gray, 1845 (Squamata, Phyllodactylidae) in an Atlantic Forest remnant in north‐eastern Brazil
Authors: Oitaven Leonardo P. C. , Grossi Paschoal Coelho , Tinoco Moacir Santos , Ribeiro Felipe da Silva , de Moura Geraldo Jorge Barbosa
Published: February 2023

Ecological aspects are essential for testing hypotheses about the characteristics, evolutionary processes and behaviour patterns of different taxa. However, for many neotropical lizards, like Gymnodactylus darwinii, such information is scant in the literature. This lizard is endemic to the Atlantic rainforest, occurring from Rio Grande do Norte to São Paulo. Herein, the aspects of trophic ecology, microenvironmental specificity and sexual dimorphism were analysed from 65 collected individuals and 15 sighted individuals in two conservation units: Camucim and Tapacurá, located in São Lourenço da Mata, north‐eastern region of Brazil. The data found classify G. darwinii as a saxicolous lizard, with a preference for rocky outcrops, without sexual dimorphism. According to its trophic ecology, the species is considered a generalist and sit–wait forager. Arthropods, especially Orthoptera and Araneae, dominate the lizard's diet. Neither of these aspects differed between seasons. The present study also shows the importance of the domain conservation, with the aim to provide resources for many vertebrates, especially endemic species.
ESG and volatility risk: International evidence
Authors: Sabbaghi Omid
Published: February 2023

This study examines the volatility risk for firms that are rated high on environmental, social, and governance (ESG) dimensions in emerging markets and developed markets outside the United States and Canada. Employing the Morgan Stanley Capital International (MSCI) ESG Leader indices, this study investigates the impact of good news and bad news on the volatility risk for the highest ESG‐rated firms through multivariate DCC‐EGARCH modeling. This study finds that the impact of a negative news shock of size 2 standard deviations is approximately 45% higher than that of a positive news shock of the same size for the case of the developed markets under interest. With respect to emerging markets, this study reports that the impact of a negative news shock of size 2 standard deviations is 41% higher than that of a positive news shock of the same size. The results provide empirical evidence in support of the hypothesis that the volatility impact of news for high ESG‐rated firms in developed markets and emerging markets is larger for bad news compared to good news, and the results are robust across time. The empirical findings underline the importance of reporting‐related disclosures of ESG initiatives, and provide seminal evidence of a slow response to news by high ESG‐rated firms in emerging markets.
Ethical judgments in the sharing economy: When consumers misbehave, providers complain
Authors: Culiberg Barbara , Čater Barbara , Abosag Ibrahim , Gidaković Petar
Published: February 2023

The complex triadic relationships among consumers, providers, and platforms in the sharing economy have led to increasing conflicts in the interactions between the actors involved, especially when it comes to unethical behavior, such as rule breaking by consumers. This paper examines consumer misbehavior from the perspective of their peers, i.e., service providers. In two studies (an experiment and a survey, combined N = 452), we observe a significant positive effect of ethical climate and a significant negative effect of trust in consumers on providers' strictness of ethical judgments of consumer misbehavior and through this on negative word of mouth. Further, the survey results show that the relationship between the strictness of ethical judgments and negative word of mouth is only significant for providers with low or medium levels of trust in the platform. The results highlight the importance of regulating consumer misbehavior in the sharing economy.