bluuebunny/crossref_metadata_2025 huggingface dataset:
Geldanamycin treatment does not result in anti-cancer activity in a preclinical model of orthotopic mesothelioma
Authors: Orozco Morales M. Lizeth , Rinaldi Catherine A. , de Jong Emma , Lansley Sally M. , Gary Lee Y. C. , Zemek Rachael M. , Bosco Anthony , Lake Richard A. , Lesterhuis W. Joost
Published: August 2022

Mesothelioma is characterised by its aggressive invasive behaviour, affecting the surrounding tissues of the pleura or peritoneum. We compared an invasive pleural model with a non-invasive subcutaneous model of mesothelioma and performed transcriptomic analyses on the tumour samples. Invasive pleural tumours were characterised by a transcriptomic signature enriched for genes associated with MEF2C and MYOCD signaling, muscle differentiation and myogenesis. Further analysis using the CMap and LINCS databases identified geldanamycin as a potential antagonist of this signature, so we evaluated its potential in vitro and in vivo. Nanomolar concentrations of geldanamycin significantly reduced cell growth, invasion, and migration in vitro. However, administration of geldanamycin in vivo did not result in significant anti-cancer activity. Our findings show that myogenesis and muscle differentiation pathways are upregulated in pleural mesothelioma which may be related to the invasive behaviour. However, geldanamycin as a single agent does not appear to be a viable treatment for mesothelioma.
Diversity and functional analysis of rumen and fecal microbial communities associated with dietary changes in crossbreed dairy cattle
Authors: Kibegwa Felix M. , Bett Rawlynce C. , Gachuiri Charles K. , Machuka Eunice , Stomeo Francesca , Mujibi Fidalis D.
Published: August 2022

The objective of this study was to investigate the effect of varying roughage and concentrate proportions, in diet of crossbreed dairy cattle, on the composition and associated functional genes of rumen and fecal microbiota. We also explored fecal samples as a proxy for rumen liquor samples. Six crossbred dairy cattle were reared on three diets with an increasing concentrate and reducing roughage amount in three consecutive 10-day periods. After each period, individual rumen liquor and fecal samples were collected and analyzed through shotgun metagenomic sequencing. Average relative abundance of identified Operational Taxonomic Units (OTU) and microbial functional roles from all animals were compared between diets and sample types (fecal and rumen liquor). Results indicated that dietary modifications significantly affected several rumen and fecal microbial OTUs. In the rumen, an increase in dietary concentrate resulted in an upsurge in the abundance of Proteobacteria, while reducing the proportions of Bacteroidetes and Firmicutes. Conversely, changes in microbial composition in fecal samples were not consistent with dietary modification patterns. Microbial functional pathway classification identified that carbohydrate metabolism and protein metabolism pathways dominated microbial roles. Assessment of dietary effects on the predicted functional roles of these microbiota revealed that a high amount of dietary concentrate resulted in an increase in central carbohydrate metabolism and a corresponding reduction in protein synthesis. Moreover, we identified several microbial stress-related responses linked to dietary changes.BacteroidesandClostridiumgenera were the principal hosts of these microbial functions. Therefore, the roughage to concentrate proportion has more influence on the microbial composition and microbial functional genes in rumen samples than fecal samples. As such, we did not establish a significant relationship between the rumen and fecal metagenome profiles, and the rumen and fecal microbiota from one animal did not correlate more than those from different animals.
Cardiomyocyte alpha-1A adrenergic receptors mitigate post-infarct remodeling and mortality by constraining necroptosis
Authors: Zhang Jiandong , Sandroni Peyton B. , Huang Wei , Oswalt Leah , Smith Alan J. , Ash Tyler , Lee Sung-Hoo , Shih Yen-Yu I. , Rossi Joseph S. , Huang Hsiao-Ying S. , Myagmar Bat E. , Simpson Paul C. , Schisler Jonathan C. , Jensen Brian C.
Published: August 2022

Activation of alpha-1-adrenergic receptors (α1-ARs), particularly the α1A subtype, protects the murine heart against injury, whereas human studies show that α1-AR antagonists (α-blockers) may increase the risk of heart failure. We created a cardiomyocyte-specific α1A-AR knockout mouse (cmAKO) to define the mechanisms underlying these effects and to elucidate whether they arise from cardiomyocyte α1A-ARs or systemic factors. Myocardial infarction (MI) resulted in 70% 7-day mortality in cmAKO compared to 10% in wild type (WT) mice. cmAKO mice exhibited exaggerated ventricular remodeling and increased cell death compared to WT mice 3 days post-MI, coupled to upregulation of canonical mediators of necroptosis: receptor-interacting protein (RIP) kinases RIP1 and RIP3 and mixed lineage kinase domain-like protein. An α1A-AR agonist mitigated ischemia-induced cardiomyocyte death and necroptotic signaling in vitro. A RIP1 antagonist abrogated the protective effects of α1A activation in vivo and in vitro. We found that patients at our center who were taking α-blockers at the time of MI experienced a higher risk of mortality (hazard ratio 1.53, p=0.029) during 5-year follow-up, providing clinical correlation for our experimental data. Collectively our findings indicate that cardiomyocyte α1A-ARs constrain ischemia-induced necroptosis and suggest caution in the use of α-blockers in patients at risk for MI.
Deep Neural Networks Predict MHC-I Epitope Presentation and Transfer Learn Neoepitope Immunogenicity
Authors: Albert Benjamin Alexander , Yang Yunxiao , Shao Xiaoshan M. , Singh Dipika , Smith Kellie N. , Anagnostou Valsamo , Karchin Rachel
Published: August 2022

Identifying neoepitopes that elicit an adaptive immune response is a major bottleneck to developing personalized cancer vaccines. Experimental validation of candidate neoepitopes is extremely resource intensive, and the vast majority of candidates are non-immunogenic, making their identification a needle-in-a-haystack problem. To address this challenge, we present computational methods for predicting MHC-I epitopes and identifying immunogenic neoepitopes with improved precision. The BigMHC method comprises an ensemble of seven pan-allelic deep neural networks trained on peptide-MHC eluted ligand data from mass spectrometry assays and transfer learned on data from assays of antigen-specific immune response. Compared with four state-of-the-art classifiers, BigMHC significantly improves the prediction of epitope presentation on a test set of 45,409 MHC ligands among 900,592 random negatives (AUROC=0.9733, AUPRC=0.8779). After transfer learning on immunogenicity data, BigMHC yields significantly higher precision than seven state-of-the-art models in identifying immunogenic neoepitopes, making BigMHC effective in clinical settings. All data and code are freely available athttps://github.com/KarchinLab/bigmhc.
Polycomb response elements reduce leaky expression of Cas9 under temperature-inducibleHsp70Bbpromoter inDrosophila melanogaster
Authors: Warsinger-Pepe Natalie , Chang Carly , Desroberts Connor R. , Akbari Omar S.
Published: August 2022

Heat shock inducible expression of genes through the use of heat inducible promoters is commonly used in research despite leaky expression of downstream genes of interest without targeted induction (i.e. heat shock). The development of non-leaky inducible expression systems are of broad interest for both basic and applied studies, to precisely control gene expression. Here we characterize the use of Polycomb response elements and the inducibleHeat shock protein 70Bbpromoter, previously described as a non-leaky inducible system, to regulate Cas9 endonuclease levels and function inDrosophila melanogasterafter varying both heat shock durations and rearing temperatures. We show that Polycomb response elements can significantly reduce expression ofCas9underHeat shock protein 70Bbpromoter control using a range of conditions, corroborating previously published results. We further demonstrate that this low transcript level of heat-inducedCas9is sufficient to induce mutant mosaic phenotypes. Incomplete suppression of an inducibleCas9system by Polycomb response elements with no heat shock suggests that further regulatory elements are required to precisely controlCas9expression and abundance.
Enhancer-promoter interactions form independently of genomic distance and are functional across TAD boundaries
Authors: Pinto Pedro Borges , Grasso Alexia , Balasubramanian Deevitha , Vincent Séverine , Tarayre Hélène , Lajoignie Damien , Ghavi-Helm Yad
Published: August 2022

Developmental enhancers are essential regulatory elements that drive precise spatio-temporal gene expression patterns. They do so by interacting with the promoter of their target genes, often across large genomic distances, in a highly specific manner. However, it is unclear how such specificity can be achieved. While several studies have suggested that Topologically Associating Domains (TADs)1–3 facilitate and constrain enhancer-promoter interactions, the role of TAD boundaries in effectively restricting enhancer-promoter interactions is heavily debated. Here we show that enhancers can establish long-range interactions across TAD boundaries and even between different chromosomes. Moreover, some of these interactions are functional in vivo, illustrating their functional importance. Using the twist locus in Drosophila embryos, we systematically relocated one of its enhancers to different regulatory contexts and distances from the twist promoter. We found that the twist promoter can engage in functional enhancer-promoter interactions across a TAD boundary and that distal interactions are sometimes favored over proximal ones. Our results demonstrate that TAD boundaries are not sufficient to constrain enhancer-promoter interactions and that the formation of long-range interactions is not solely driven by distance. These observations suggest that other general mechanisms must exist to establish and maintain specific enhancer-promoter interactions across large distances.
Whether the audit expectation-performance gap is expanding amid changes in audit landscape? New evidence from an emerging economy
Authors: Kumari J.S. , Ajward Roshan
Published: August 2022

Purpose

The purpose of this study is to provide fresh insights into whether there is an expectation gap between external auditors' and other stakeholders' perceptions of external auditors' responsibilities in an emerging economy, in light of recent changes to the global audit landscape.

Design/methodology/approach

A quantitative approach in the positivistic paradigm was adopted, and a structured questionnaire was used to gather data.

Findings

The findings suggested that there was a statistically significant discrepancy between external auditors' and social groups' perceptions of the responsibilities of external auditors. More than half of the gap was due to deficiency in standards, 19% due to unreasonable expectations by society, while 25% of the gap was found to be due to deficient performance.

Research limitations/implications

The study focused on the duties of external auditors and not on the duties of other types of auditors while examining the audit expectation-performance gap (AEG), and this was due to the drastic differences in the scope of their duties.

Practical implications

The findings of this study are likely to have direct policy implications for regulators, authorities, educators and auditing professionals, who should take immediate actions and measures to reduce the AEG in light of the current global audit landscape advancements and changes.

Originality/value

The present study used a substantially updated model to measure the AEG to suit the contemporary changes in the auditing landscape, and could be considered as a pioneering study that measures the AEG in an emerging economy amid recent changes.
Examining the role of team climate, transactive memory system, and team leader humility in teams: an empirical study of Indian generational cohorts
Authors: Maan Pratibha , Srivastava Dinesh Kumar
Published: August 2022

Purpose

The study aims to define the term “generation” by proposing an integrated design based on age-period-cohort effects and by proposing an Indian generational cohort framework categorizing Indian generational cohorts into four categories, namely, Baby Boomers, GenX, GenY, and GenZ. The study further aimed to capture the existing generational differences between GenY and GenZ cohorts in the Indian teams on team climate, transactive memory system, and team leader humility.

Design/methodology/approach

For the first two objectives a literature review methodology along with the author's proposition was adopted. An integrated design was proposed by reviewing the relevant sociological literature to define generations. Thereafter, an Indian cohort framework was proposed categorizing them into four groups Baby Boomers, GenX, GenY, and GenZ. Following that, for the last objective, i.e. to identify the differences between cohorts, empirical data were collected by a structured questionnaire that was disseminated to GenY and GenZ Indian working professionals. A total of 229 responses were used for observing the differences or similarities between GenY and GenZ cohorts on the study variables by employing an independent samples t-test.

Findings

The study proposed an integrated design (age, period, and cohort effect). Following that, an Indian generational cohort's framework has been outlined categorizing Indian cohorts based on their birth years, age groups, developmental stages, formative years, major Indian historical events, and various characteristics possessed by them. Moreover, the empirical findings support the existing generational disparities and depict that GenZ holds a higher inclination towards transactive memory systems and team climate whereas GenY holds more inclination toward leader humility.

Practical implications

The study put forth its contribution to research scholars by categorizing Indian generational cohorts in a rationalized manner based on an integrated design (age-period-cohort) effect. The study would further assist concerned authorities and managers in formulating HR policies to deal with the underlying generational differences highlighted by the study.

Originality/value

As there lies a paucity of generational frameworks in the Indian context, this study is the first attempt in this direction which categorizes Indian generational cohorts based on a unique integrated design including age-period-cohort effects. In addition, the study also investigated these cohorts in Indian organizations to observe the existing variations.
Sociotechnical dimensions of BIM-induced changes in stakeholder management of public and private building projects
Authors: Mani Saba , Ahmadi Eftekhari Navid , Hosseini M. Reza , Bakhshi Javad
Published: August 2022

Purpose

This paper aims to explore the various sociotechnical dimensions of building information modelling (BIM)-induced changes associated with stakeholder management of projects.

Design/methodology/approach

This paper relies on grounded theory and data collection from two case studies – one in the public sector and one in the private sector – and is underpinned by Leavitt’s (1964) sociotechnical model.

Findings

Findings reveal four new dimensions of stakeholder management as being affected through BIM-induced changes: commitment; transparency; learning and experience; and stakeholder satisfaction, with these extending beyond the dimensions recognised in the existing literature. Another novelty lies in bringing to light the highly context-specific nature of BIM-induced changes pertinent to stakeholder management, with the two case studies demonstrating differences in these changes. Furthermore, a theoretical model of the causal impacts of various identified dimensions is presented, in which the sequence of changes and the causal associations between the identified dimensions are conceptualised.

Originality/value

Through Leavitt’s (1964) Diamond lens, the procedure of change and its evolutionary procedure for various components of the sociotechnical system of stakeholder management are theorised. The tentative conceptualisations presented offer a springboard from which to further investigate the episode of change pertinent to various dimensions of stakeholder management in BIM-enabled projects.
Understanding the effects of educational decentralization through the perspectives of education managers and teachers
Authors: Khilji Gulab , Jogezai Nazir Ahmed , Bibi Nadra , Baloch Fozia Ahmed
Published: August 2022

Purpose

The study was designed to investigate the effects of the decentralization of education through the perceptions of education managers.

Design/methodology/approach

This was a qualitative case study research. The decentralization notification of 2014, issued by the secondary education department, Government of Balochistan, Pakistan was taken as a case. Some administrative and financial powers were devolved at cluster and district levels through this notification. In pursuance of data collection, focus group discussions were conducted with 20 education managers, 20 teachers, and 5 high-ranked education policy actors. The gathered data were analyzed using thematic analysis.

Findings

The study found that the intent of the decentralization move was positive, where some of the issues of teachers are now resolved at district and school levels. However, academic decentralization was utterly neglected. Furthermore, with the inclusion of district administration in the education decision-making, powers seem to be recentralized. The study concluded that decentralization should occur through a proper legislative process based on sound planning. There should be a balance between central authorities and local/district-level education management in education management and decision-making.

Research limitations/implications

The study adds to the existing literature relating to education management and informs education managers, teachers, school principals, and policy actors for research-based and informed decision-making.

Originality/value

This study was conducted in a developing country to understand the effects of decentralized education management. The authors declare the organicity of the data. The authors also declare that the paper has not been submitted to any other journal or in review elsewhere.
Food labelling and safety consciousness of consumers in Ghana: the case of tinned tomatoes
Authors: Bannor Richard Kwasi , Amfo Bismark , Oppong-Kyeremeh Helena
Published: August 2022

Purpose

With the empirical evidence on the purchase behaviour of tinned tomatoes, food labelling and the safety consciousness of consumers in Ghana were examined.

Design/methodology/approach

Primary data were obtained from 130 consumers. Descriptive statistics, factor analysis and multinomial probit analysis were applied.

Findings

Consumers use tinned tomatoes for cooking because of its easy accessibility in nearby shops, guaranteed constant supply, attractive package, it being affordable/cheaper, its better colour, advertisement/promotion, and longer shelf life. There is a low level of food safety consciousness among consumers since only one-fifth read labels on tinned tomatoes very often, and one-fifth do not read labels at all. Consumers frequently check on tinned tomatoes' most essential information: brand/type, manufacturing and expiry dates, and weight/volume. Age, residential status, contact information, nutritional benefits and affordability influence the choice of retail brand of tinned tomatoes. The health label consumer segment and conventional label consumer segment were identified, with the majority being the former.

Research limitations/implications

The sample size used for the study could be improved in terms of number and geographical coverage. This is because the study was limited to only one main urbanised area in Ghana. Therefore, it will be worthwhile for a further study to be conducted by comparing urban and rural consumers in Ghana and other countries within Africa, to either validate or reveal a different trajectory of consumer behaviour relevant to marketing, policy and practice.

Originality/value

Tomato paste (tinned tomatoes) is consumed in almost all homes in Africa, but there are food scare concerns about tinned tomatoes due to reported cases of adulteration with unhealthy materials such as starch and food colour, leading to negative health implications on consumers. This makes the reading of tinned tomato labels very crucial. Thus, it is of policy relevance to investigate consumers' reading behaviour of label information on tinned tomatoes in Ghana. However, previous studies on food labelling focussed on food and nutrition labelling and implications of food labelling on consumers' purchase behaviour, with most of them outside Africa.
International portfolio investment: does the uncertainty matter?
Authors: Nguyen Phuc Canh , Schinckus Christophe , Nguyen Binh Quang , Tran Duyen Le Thuy
Published: August 2022

Purpose

This study investigates the effect of global and domestic uncertainty on the dynamics of portfolio investment in 21 economies (mostly advanced and larger emerging economies) from 2001–2016.

Design/methodology/approach

Specifically, the evolution of the net portfolio equity investment inflows (FPI net inflows) and the evolution of net portfolio investment (FPI net) are investigated in a context in which the degree and the volatility of domestic economic policy uncertainty (EPU) and world uncertainty index (WUI) varied. The authors provide an empirical analysis through the sequential (two-stage) estimation of linear panel data models for unbalanced panel data.

Findings

An increase in the degree and volatility of domestic EPU has a significant negative influence on FPI net inflows, while an increase in WUI has a significant positive one. Notably, a simultaneous increase in the domestic EPU and WUI enhances the net inflows of FPI, whereas a simultaneous increase in the volatility of these indicators reduces the net inflows of FPI. An increase in the degree and volatility of both domestic EPU and WUI have a significant positive effect on the net portfolio investment, implying that a significant net portfolio investment is going out of the country.

Research limitations/implications

The results of this study encourage international investors to consider uncertainty indicators (and, more specifically, their variations) in their portfolio strategy to optimize their position on the international markets. The findings of this study invite policy-makers from large countries to reduce the perceived domestic uncertainty since this parameter can influence international investors' sensitivity and willingness to diversify their position out of the country.

Originality/value

The authors' approach focuses on the variations of uncertainty (existing literature mainly works with the indicators). While the results confirm the role played by large markets in international portfolio investment management, it nuances the changes in the portfolio management behaviors toward other markets when facing a changing uncertainty.
Toward sustainable agriculture: the case of a sustainable farm in Egypt
Authors: Abdelrazek Nour Adham , El Khafif Mahmoud Khairat
Published: August 2022

Purpose

With less than ten years left to accomplish the United Nations (UN) Sustainable Development Agenda 2030, there is a pressing need to develop innovative sustainable methods and/or techniques that agriculture and food businesses can apply to improve natural resource efficiency. Therefore, the purpose of the current study is to review sustainable agriculture in one of the developing Arab countries by presenting a real-life example of a sustainable farm.

Design/methodology/approach

The current study aims to showcase a sustainable farm in one of the developing Arab countries, utilizing a case study methodology. The case study methodology is particularly appropriate within the current research context to provide an in-depth and multi-faceted understanding of sustainable agriculture practices.

Findings

The findings of the current study delineate the different dimensions of sustainable agriculture which includes water savings, less usage of artificial fertilizers, reduction of pesticides and use of renewable energy. In addition, the current study shows that the application of the different sustainable agriculture practices results in substantial savings on the economic levels as well as the environmental levels.

Originality/value

There are two valuable outcomes from this research. The first is a framework for understanding the different dimensions of sustainable agriculture. The second outcome is highlighting various implications for sustainable entrepreneurs who wish to accelerate the transition to sustainable agriculture.
Healthcare Professionals’ Perceptions of Stabilized Edible Foam with Adults with Severe Dysphagia; an exploratory study
Authors: Hepper Elizabeth C. , Patterson Joanne M.
Published: August 2022

Background

Improving the quality of life for individuals with severe dysphagia is a priority when considering new areas of dysphagia management, especially if this increases opportunities to participate in social activities associated with eating and drinking. Edible foam is widely researched and available in the food industry; however, the use of edible foam within the field of dysphagia remains unexplored. Despite no research published on effectiveness and safety, a commercial product currently on the market is widely distributed across both Europe and the UK, including 28 NHS Trusts, suggesting that it is increasingly being used in clinical practice.

Aims

To explore the perceptions and experiences of healthcare professionals on the use of stabilized edible foam (SEF) with adults with severe dysphagia in order to inform areas for future research in this novel dysphagia intervention.

Methods & Procedures

Healthcare professionals were recruited using purposeful sampling and snowballing technique. A total of 56 healthcare professionals were initially approached, of which 10 completed the semi‐structured interviews. Interview questions were developed from a topic guide and a pilot questionnaire.

Outcomes & Results

Thematic analysis was used to identify three themes: potential impact, consideration of risk and perceived experiences. Overarching each of these themes was the element of the unknown.

Conclusions & Implications

Use of SEF with adults with dysphagia is in its infancy. Whilst results indicate that some clinicians are embracing this novel approach, others express concerns. Therefore, further research is needed, particularly in relation of direct experience of individuals and contra‐indications.

What this paper adds

What is already known on the subject

The use of SEF with individuals with swallowing problems is a relatively novel area of dysphagia intervention in the UK. There are currently no published studies on its effectiveness and safety profile.

What this paper adds to existing knowledge

This study provides valuable preliminary work into the area of SEF and adults with severe dysphagia, capturing the experience and perceptions of healthcare professions who have an awareness of SEF.

What are the potential or actual clinical implications of this work?

Increasing clinicians and researcher's awareness of this novel area of dysphagia management.
Rise of the Androids: The Reflection of Developers’ Characteristics in Computerized Systems
Authors: Sobolev Daphne
Published: August 2022

Due to their speed and accuracy, computerized decision‐making and data‐analysis systems are often perceived to be close to the ideal of unbounded rationality. Challenging this perception, this study explores the possibility that computerized systems reflect the individual characteristics of the developers who have designed and realized them. Through the analysis of interviews with high‐frequency trading system developers and a survey of software developers working in diverse industries, it shows that developers’ characteristics, which have been related to bounded rationality (e.g. experience and expertise), influence their codes’ performance and errors. Computer codes also reflect the personal circumstances of the developers (e.g. deadlines and stress), and their values. However, whereas some developers value code characteristics that are congruent with the ideal of unbounded rationality, including speed and accuracy, others aim to achieve characteristics that could be incongruent with it (e.g. code readability and modularity). Developers’ roles and organizational practices, such as testing procedures and code reviews, limit the expression of their characteristics in their codes. Nevertheless, developers can be often identified by reading the codes. Highlighting that developers transfer some of their characteristics to their codes, this study identifies elements of bounded rationality in decision‐making systems and extends organizational decision‐making research.
Guidelines for standardizing the application of discriminant analysis of principal components to genotype data
Authors: Thia Joshua A.
Published: August 2022

Despite the popularity of discriminant analysis of principal components (DAPC) for studying population structure, there has been little discussion of best practice for this method. In this work, I provide guidelines for standardizing the application of DAPC to genotype data sets. An often overlooked fact is that DAPC generates a model describing genetic differences among a set of populations defined by a researcher. Appropriate parameterization of this model is critical for obtaining biologically meaningful results. I show that the number of leading PC axes used as predictors of among‐population differences, paxes, should not exceed the k−1 biologically informative PC axes that are expected for k effective populations in a genotype data set. This k−1 criterion for paxes specification is more appropriate compared to the widely used proportional variance criterion, which often results in a choice of paxes ≫ k−1. DAPC parameterized with no more than the leading k−1 PC axes: (i) is more parsimonious; (ii) captures maximal among‐population variation on biologically relevant predictors; (iii) is less sensitive to unintended interpretations of population structure; and (iv) is more generally applicable to independent sample sets. Assessing model fit should be routine practice and aids interpretation of population structure. It is imperative that researchers articulate their study goals, that is, testing a priori expectations vs. studying de novo inferred populations, because this has implications on how their DAPC results should be interpreted. The discussion and practical recommendations in this work provide the molecular ecology community with a roadmap for using DAPC in population genetic investigations.
Not just the Big Five: African ecotourists prefer parks brimming with bird diversity
Authors: Eyster H. N. , Naidoo R. , Chan K. M. A.
Published: August 2022

Ecotourism helps sustain protected areas (PAs) that in turn conserve Africa's declining fauna. Identifying ecotourist preferences and which species and landscapes benefit from ecotourism could therefore support African biodiversity conservation efforts. Due to historic associations with trophy hunting and subsequent ecotourism marketing efforts, ecotourist preferences have been thought to traditionally center around the ‘Big Five’: elephant, lion, buffalo, leopard, and rhinoceros. But these preferences may be evolving. Here, we ask two questions, one about the drivers and one about the consequences of ecotourism: (1) Which species and landscapes do ecotourists most prefer based on realized visitation data? And (2), differently, which species and landscapes benefit most from ecotourism? We gathered data on average annual tourist visits, the occurrence of nine mammals, bird species richness, forest cover, national wealth, local human population and accessibility for 164 Sub‐Saharan African PAs. To address our first question, we used a Bayesian multivariable model to identify whether bird and megafaunal diversity explain visits to PAs while controlling for other factors. To address our second question, we used Bayesian univariate models to analyze the relationships between park visitation and each species/landscape. We found that tourist preferences extend beyond the Big Five to include bird diversity. We also observed that ecotourism may be well suited to conserve bird diversity, lion, cheetah, black and white rhinoceros, African wild dog and giraffe species. Collectively, our results may help inform how to leverage ecotourism to conserve African fauna.
Cholinergic signaling impairs cardiomyocyte cohesion
Authors: Yeruva Sunil , Körber Lars , Hiermaier Matthias , Egu Desalegn T. , Kempf Ellen , Waschke Jens
Published: August 2022

Aim

Cardiac autonomic nervous system (ANS) dysregulation is a hallmark of several cardiovascular diseases. Adrenergic signaling enhanced cardiomyocyte cohesion via PKA‐mediated plakoglobin phosphorylation at serine 665, referred to as positive adhesiotropy. This study investigated cholinergic regulation of cardiomyocyte cohesion using muscarinic receptor agonist carbachol (CCH).

Methods

Dissociation assays, Western blot analysis, immunostaining, atomic force microscopy (AFM), immunoprecipitation, transmission electron microscopy (TEM), triton assays, and siRNA knockdown of genes were performed in either HL‐1 cells or plakoglobin (PG) wild type (Jup+/+) and knockout (Jup−/−) mice, which served as a model for arrhythmogenic cardiomyopathy.

Results

In HL‐1 cells grown in norepinephrine (NE)‐containing medium for baseline adrenergic stimulation, and murine cardiac slice cultures from Jup+/+ and Jup−/− mice CCH treatment impaired cardiomyocyte cohesion. Immunostainings and AFM experiments revealed that CCH reduced desmoglein 2 (DSG2) localization and binding at cell borders. Furthermore, CCH reduced intercalated disc plaque thickness in both Jup+/+ and Jup−/−mice, evidenced by TEM analysis. Immunoprecipitation experiments in HL‐1 cells revealed no changes in DSG2 interaction with desmoplakin (DP), plakophilin 2 (PKP2), PG, and desmin (DES) after CCH treatment. However, knockdown of any of the above proteins abolished CCH‐mediated loss of cardiomyocyte cohesion. Furthermore, in HL‐1 cells, CCH inhibited adrenergic‐stimulated ERK phosphorylation but not PG phosphorylation at serine 665. In addition, CCH activated the AKT/GSK‐3β axis in the presence of NE.

Conclusion

Our results demonstrate that cholinergic signaling antagonizes the positive effect of adrenergic signaling on cardiomyocyte cohesion and thus causes negative adhesiotropy independent of PG phosphorylation.
A stewardship program to facilitate anticholinergic and sedative medication deprescribing using the drug burden index in electronic medical records
Authors: Masnoon Nashwa , Lo Sarita , Hilmer Sarah
Published: August 2022

Aims

The drug burden index (DBI) measures a person's total exposure to anticholinergic and sedative medications, which are commonly associated with harm. Through incorporating the DBI in electronic medical records (eMR) and implementing a DBI stewardship program, we aimed to determine (i) uptake of the steward's recommendations to deprescribe anticholinergic and/or sedative drugs by the medical team and (ii) whether accepted recommendations were actioned in hospital or recommended for follow‐up by the General Practitioner post‐discharge.

Methods

A single‐arm, non‐randomised feasibility study was performed at an Australian tertiary referral metropolitan hospital. The stewardship pharmacist reviewed eMRs of patients aged ≥75 years with DBI scores > 0, during admission. The steward identified and discussed potential opportunities to deprescribe anticholinergic and/or sedative medications with the medical registrars.

Results

Amongst 256 patients reviewed, the steward made 170 recommendations for 117 patients. Registrars agreed with 141 recommendations (82.9%) for 95 patients (81.2%), and actioned 115 deprescribing recommendations for 80 patients, most commonly for antidepressants and opioids. The 115 actioned recommendations resulted in 125 changes, with 44 changes to the inpatient drug chart and 81 additional changes recommended post‐discharge in the discharge summary.

Conclusion

Opportunities exist for deprescribing anticholinergic and sedative medications in older inpatients and a DBI stewardship program may help implement these. It is important to capture different outcomes of deprescribing interventions, including in‐hospital medication changes, recommendations in the Discharge Summary, sustainability of deprescribing and clinical outcomes.
Does the size of foreign population in a city affect the level of labour‐market discrimination against job applicants of migrant origin?
Authors: Ahmad Akhlaq
Published: August 2022

Based on a correspondence experiment, this article examines if the size of population of foreign background in a city exerts any significant effect on the extent of labour‐market discrimination faced by job applicants of migrant origin. The study results find neither any statistically significant relationship between the two, nor do they lend support to the group threat and group contact conceptual frameworks. Rather, they appear to corroborate the pure discrimination model, as discrimination seems to be uniformly spread over all cities and all types of jobs with different characteristics. However, the findings of this study do not exclude the possibility that there could be a threshold value in the share of foreign population after which the picture of discrimination would become richer in nuances and some of the theories would gain more explanatory power.
Condyloma and coincidental epidermodysplasia verruciformis acanthoma positive for human papillomavirus‐14 and ‐21
Authors: Bartley Brooke , Cho Woo Cheal , Rady Peter L. , Dai Julia , Curry Jonathan L. , Milbourne Andrea , Tyring Stephen K. , Torres‐Cabala Carlos A.
Published: August 2022

Epidermodysplasia verruciformis (EDV) is a rare genodermatosis that predisposes individuals to persistent infection with β‐human papillomavirus (HPV) genotypes. The term EDV acanthoma may be applied to lesions with incidental findings of EDV‐defining histopathological features without clinical signs of EDV. We report a case of HPV‐14‐ and ‐21‐positive EDV acanthoma arising in association with condyloma in a female patient with a history of low‐grade squamous intraepithelial lesion of the cervix positive for high‐risk HPV (non‐16/18), chronic kidney disease, and systemic lupus erythematosus. The patient had no family or personal history of EDV, but the patient was on immunosuppressive therapy with mycophenolate mofetil and prednisone. A biopsy specimen from one of the perianal lesions revealed histopathologic changes consistent with EDV in the setting of condyloma. Molecular testing showed HPV‐14 and ‐21, which supported the coexistence of condyloma with EDV acanthoma.
Novel traction and mucosal defect closure methods using clip‐traction bands for duodenal endoscopic submucosal dissection
Authors: Tashima Tomoaki , Ishikawa Tsubasa , Ryozawa Shomei
Published: August 2022

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The relation between aggression and theory of mind in children: A meta‐analysis
Authors: Wang Yiyi , Shang Siyuan , Xie Wanze , Hong Skylar , Liu Zexi , Su Yanjie
Published: August 2022

Previous findings on the association between theory of mind (ToM) and aggression in children are mixed. The social skills deficit view regarded ToM as a single‐edged sword and proposed that a lack of ToM can lead to aggression, while the double‐edged sword view proposed that children with advanced ToM can still show much aggression because children can also leverage ToM to harm others. To resolve the dispute between the two views, we conducted a meta‐analysis combining cross‐sectional and longitudinal findings from 53 studies including a total of 11,579 children aged between 2 and 15 years. The overall negative correlation between ToM and aggression was small but significant (r = −0.08). The negative correlation was robust, with the magnitude of the correlation being similar across physical versus relational aggression, proactive versus reactive aggression, cognitive versus affective ToM, preschoolers versus school‐aged children, different aggression measurements, and different levels of societal individualism. Moreover, the negative correlation was found regardless of whether ToM and aggression were measured concurrently or at different time points, but the correlation was the largest when ToM was measured before aggression. Whether the aggression was bullying or not also moderated the association, with ToM only being negatively related to non‐bullying aggression but not bullying. Together, these findings suggest that ToM is a single‐edged sword to decrease general aggression and that aggression might also give rise to lower ToM capacity during development.

Research Highlights

This study systemically reviewed the existing mixed findings on the association between aggression and ToM during childhood using a meta‐analysis.

There was a negative correlation between ToM and aggression in children aged between 2 and 15 years.

The negative correlation between aggression and ToM was stronger when ToM was measured first, followed by aggression, than vice versa.

There was a negative correlation between non‐bullying aggression and ToM, whereas there was no correlation between bullying and ToM.
Prognostic value of soluble urokinase‐type plasminogen activator receptor in coronary artery disease: A meta‐analysis
Authors: Li Yang , Ding Yaqun , Zhao Yinjie , Gui Yongqing , Shen Yajing , Xiang Qiang
Published: August 2022

Background

A potential inflammatory biomarker, soluble urokinase‐type plasminogen activator receptor (suPAR) has been utilized to assist the prognostic assessment of coronary artery disease (CAD) patients; however, outcomes have been inconsistent. The prognostic relevance of suPAR as a predictor of CAD patient adverse outcomes was therefore examined.

Methods

Research articles published as of 1 January 2022 were retrieved from PubMed, Embase, the Web of Science and the Cochrane Library. All‐cause mortality, cardiovascular mortality and other major cardiovascular events (nonfatal myocardial infarction, heart failure or stroke) were analysed as a subset of relevant studies' results. We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for each study. The broad EQUATOR guidelines were conformed. Risk of bias was assessed with ROBINS‐I tool.

Results

In total, this analysis included nine studies including 14,738 CAD patients. All included studies made a correction for certain potential confounders. However, risk of bias ranged from moderate to critical. When the ROBINS‐I tool was used. Patients with CAD that exhibited increased suPAR levels had a substantially higher risk of all‐cause mortality (HR = 2.24; 95% CI 1.97–2.55) or cardiovascular mortality (HR = 2.02; 95% CI 1.58–2.58), but not of developing other major cardiovascular events (HR = 1.63; 95% CI 0.86–3.11). Considerable heterogeneity across studies was observed in our meta‐analyses, but no significant publication bias was detected.

Conclusion

In patients with coronary disease, suPAR may have prognostic value for both all‐cause and cardiovascular mortality but not for other major cardiovascular events.
Functional traits and metacommunity theory reveal that habitat filtering and competition maintain bird diversity in a human shared landscape
Authors: Eyster Harold N. , Srivastava Diane S. , Kreitzman Maayan , Chan Kai M. A.
Published: August 2022

Human‐shared landscapes cover much of Earth, yet their conservation value is contested. This controversy may persist because previous studies have examined species diversity, rather than the processes through which such diversity is maintained. For example, a site exhibiting high diversity may not actually bolster populations if the diversity is only maintained through net immigration. Recent research has begun to isolate the processes that maintain metacommunities and develop functional trait methods to identify these processes. However, the processes underlying bird communities remain obscure. Here, we leverage metacommunity theory, functional trait partitioning and a Bayesian multispecies abundance model to assess whether a shared landscape – woody perennial polyculture farms – bolsters bird diversity. Such farms grow multiple species of food‐producing woody perennials together with vegetative groundcover. We surveyed birds and their in situ functional traits across the US Midwest in traditional agriculture, woody perennial polyculture, prairie and woods. We found that woody perennial polycultures exhibited the highest bird diversity and were the most preferred by many species (including threatened ones). Moreover, our functional trait analysis suggests that this diversity is maintained through habitat filtering and competition, rather than merely immigration. Thus, shared landscapes can likely conserve birds by providing a distinct habitat. These results suggest that woody perennial polyculture farms offer substantial potential to support bird populations in the US Midwest. Our study demonstrates the utility of in situ functional trait partitioning within a Bayesian framework to unmask ecological processes and help assess the conservation value of landscapes.
Long‐term fatigue following aneurysmal subarachnoid haemorrhage and the impact on employment
Authors: Gaastra Ben , Carmichael Harry , Galea Ian , Bulters Diederik
Published: August 2022

Background and purpose

Fatigue is common following aneurysmal subarachnoid haemorrhage (aSAH) but little is known about its frequency, prognosis and impact on employment. The aim of this study was to assess the frequency of fatigue, whether it changes over time and the relationship to employment in the long term.

Methods

This was a retrospective observational study of aSAH cases and matched controls from the UK Biobank. The presence of fatigue was compared between cases and controls using the chi‐squared test. The change in frequency over time was assessed using Spearman's rank correlation coefficient. The effect of fatigue on employment was assessed using mediation analysis.

Results

Fatigue is more common following aSAH compared to matched controls (aSAH 18.7%; controls 13.7%; χ2 = 13.0, p < 0.001) at a mean follow‐up of 123 months. Fatigue gradually improves over time with significant fatigue decreasing by 50% from ~20% in the first year to ~10% after a decade (p = 0.04). Fatigue significantly mediated 24.0% of the effect of aSAH status on employment.

Conclusions

Fatigue is common following aSAH and persists in the long term. It gradually improves over time but has a major impact on aSAH survivors, significantly contributing to unemployment following haemorrhage. Further work is required to develop treatments and management strategies for fatigue with a view to improving this symptom and consequently employment following aSAH.