bluuebunny/crossref_metadata_2025 huggingface dataset:
Charting oncogenicity of genes and variants across lineages via multiplexed screens in teratomas
Authors: Parekh Udit , McDonald Daniella , Dailamy Amir , Wu Yan , Cordes Thekla , Zhang Kun , Tipps Ann , Metallo Christian , Mali Prashant
Published: March 2021

Deconstructing tissue-specific effects of genes and variants on proliferative advantage is critical to understanding cellular transformation and to systematic selection of cancer therapeutics. Dissecting these specificities at scale requires integrated methods for multiplexed genetic screens tracking fitness across time, across human cell types, and in a suitable cellular niche since functional differences also depend on physiological cues. Towards this, we present a novel approach, harnessing single-cell cancer driver screens in teratomas coupled with hit enrichment by serial teratoma reinjection, to simultaneously screen drivers across multiple lineages in vivo. Using this system, we analyzed population shifts and lineage-specific enrichment for 51 cancer associated genes and gene variants, profiling over 100,000 cells spanning over 20 lineages, across two rounds of serially injected teratomas. We confirmed that c-MYC alone or combined with myristoylated AKT1 potently drives proliferation in progenitor neural lineages, demonstrating signatures of malignancy. These drivers directed teratoma development to lineages representative of pediatric tumors such as medulloblastoma and rhabdomyosarcoma. Additionally, mutant MEK1S218D/S222D provides a proliferative advantage in mesenchymal lineages like fibroblasts. Our method provides a powerful new platform for multi-lineage longitudinal study of oncogenesis.
No influence of antibiotic on locomotion inDrosophila nigrosparsaafter recovery, but influence on microbiome, possibly mediating wing-morphology change
Authors: Weiland Simon O. , Detcharoen Matsapume , Schlick-Steiner Birgit C. , Steiner Florian M.
Published: March 2021

Antibiotics, such as tetracycline, has been frequently used to cure endosymbiontWolbachiain arthropods. After the symbionts had been removed, the hosts must be waited for some generations to recover from side effects of the antibiotics. Knowledge of potential long-term effects of the antibiotic is important. Here, we treatedDrosophila nigrosparsawith and without antibiotic tetracycline for three generations and two generations recovering time to investigate effects of the tetracycline on the flies concerning locomotion of larvae and adults, wing morphology, and gut microbiome of adults. In addition, gut-microbiome restoration was tested as a solution to reducing potential side effects of tetracycline on the flies’ microbiome more quickly. We found significant differences in larval and adult locomotion within groups but no significant differences among the control, antibiotic-treated, and gut-restoration groups. We found a slight differentiation of wing morphology into the three groups and significant differences in bacterial abundance among groups. The influence of tetracycline on the gut microbiome may have contributed to wing-morphology differences among groups, which would be an indirect effect of the antibiotic. Together with the absence of an effect on locomotion, this suggests that checking for both direct and indirect effects of tetracycline after a particular recovery time before using tetracycline curing is important. The microbiome of the gut-restoration group was not like that of the control group. Therefore, gut restoration cannot be used to remove effects of tetracycline inD. nigrosparsa, at least in the setup used here.
A smoothed version of the Lassosum penalty for fitting integrated risk models
Authors: Hahn Georg , Prokopenko Dmitry , Lutz Sharon M. , Mullin Kristina , Tanzi Rudolph E. , Lange Christoph
Published: March 2021

Polygenic risk scores are a popular means to predict the disease risk or disease susceptibility of an individual based on its genotype information. When adding other important epidemiological covariates such as age or sex, we speak of an integrated risk model. Methodological advances for fitting more accurate integrated risk models are of immediate importance to improve the precision of risk prediction, thereby potentially identifying patients at high risk early on when they are still able to benefit from preventive steps/interventions targeted at increasing their odds of survival, or at reducing their chance of getting a disease in the first place. This article proposes a smoothed version of the “Lassosum” penalty used to fit polygenic risk scores and integrated risk models. The smoothing allows one to obtain explicit gradients everywhere for efficient minimization of the Lassosum objective function while guaranteeing bounds on the accuracy of the fit. An experimental section on both Alzheimer’s disease and COPD (chronic obstructive pulmonary disease) demonstrates the increased accuracy of the proposed smoothed Lassosum penalty compared to the original Lassosum algorithm, allowing it to draw equal with state-of-the-art methodology such as LDpred2 when evaluated via the AUC (area under the ROC curve) metric.
In situmaturated early-stage human induced pluripotent stem cell-derived cardiomyocytes improve cardiac function by enhancing segmentary contraction in infarcted rats
Authors: Biagi Diogo , Fantozzi Evelyn Thais , Campos-Oliveira Julliana C , Naghetini Marcus Vinicius , Ribeiro Antonio F. , Rodrigues Sirlene , Ogusuku Isabella , Vanderlinde Rubia , Christie Michelle Lopes Araújo , Mello Debora B. , de Carvalho Antonio C. Campos , Valadares Marcos , Cruvinel Estela , Dariolli Rafael
Published: March 2021

The scant ability of cardiomyocytes to proliferate makes heart regeneration one of the biggest challenges of science. Current therapies do not contemplate heart re-muscularization. In this scenario, stem cell-based approaches have been proposed to overcome the lack of regeneration. We hypothesize PluriCell hiPSC-derived cardiomyocytes (hiPSC-CMs) could enhance rat’s cardiac function after myocardial infarction (MI). Animals were subjected to permanent occlusion of the Left-Ventricle (LV) anterior descending coronary artery (LAD). Seven days after MI, Early-stage hiPSC-CMs were injected intramyocardially. Rats were subjected to Echocardiography pre- and post-treatment. Thirty days after injections, treated rats displayed 6.2% human cardiac grafts, which were characterized molecularly. Left ventricle ejection fraction (LVEF) was improved by 7.8% in cell-injected rats, while placebo controls showed an 18.2% deterioration. Also, cell-treated rats displayed a 92% and 56% increase in radial and circumferential strains, respectively. Human cardiac grafts maturate in situ, preserving proliferation with 10% Ki67 and 3% PHH3 positive nuclei. Grafts were perfused by host vasculature with no evidence for immune rejection nor ectopic tissue formations. Our findings supportPluriCell hiPSC-CMsas an alternative therapy to treat MI. The next steps of preclinical development include efficacy studies in large animals on the path to clinical-grade regenerative therapy targeting human patients.
FKBP5expression is related to HPA flexibility and the capacity to cope with stressors in the house sparrow
Authors: Zimmer Cedric , Hanson Haley E. , Martin Lynn B.
Published: March 2021

The hypothalamic-pituitary-adrenal (HPA) axis and its end products, the glucocorticoids, are critical to responding appropriately to stressors. Subsequently, many studies have sought relationships between glucocorticoids and measures of health or fitness, but such relationships are at best highly context dependent. Recently, some endocrinologists have started to suggest that a focus on HPA flexibility, the ability of an individual to mount appropriate responses to different stressors, could be useful. Here, we tested the hypothesis that expression ofFKBP5, a cochaperone in the glucocorticoid receptor complex, is a simple and reliable proxy of HPA flexibility in a wild songbird, the house sparrow (Passer domesticus). We quantified HPA flexibility in a novel way, using guidance from research on heart rhythm regulation. As predicted, we found that adult sparrows with low stress-inducedFKBP5expression in the hypothalamus exhibited high HPA flexibility. Moreover, lowFKBP5expression was associated with better stress coping capacities in terms of exploratory disposition and body mass maintenance. Altogether, these results suggest thatFKBP5may be important in the regulation HPA flexibility, potentially affecting how individuals cope with natural and anthropogenic adversity.
Distinct Neural Profiles of Frontoparietal Networks in Boys with ADHD and Boys with Persistent Depressive Disorder
Authors: Vilgis Veronika , Yee Debbie , Silk Tim J. , Vance Alasdair
Published: March 2021

Working memory deficits are common in attention-deficit/hyperactivity disorder (ADHD) and depression, two common neurodevelopmental disorders with overlapping cognitive profiles but distinct clinical presentation. Multivariate techniques have previously been utilized to understand working memory processes in functional brain networks in healthy adults, but have not yet been applied to investigate how working memory processes within the same networks differ within typical and atypical developing populations. We used multivariate pattern analysis (MVPA) to identify whether brain networks discriminated between spatial vs. verbal working memory processes in ADHD and Persistent Depressive Disorder (PDD). 36 male clinical participants and 19 typically developing (TD) boys participated in a fMRI scan while completing a verbal and a spatial working memory task. Withina priorifunctional brain networks (frontoparietal, default mode, salience) the TD group demonstrated differential response patterns to verbal and spatial working memory. The PDD group showed weaker differentiation than TD, with lower classification accuracies observed in primarily the left frontoparietal network. The neural profiles of the ADHD and PDD differed specifically in the SN where the ADHD group’s neural profile suggests significantly less specificity in neural representations of spatial and verbal working memory. We highlight within-group classification as an innovative tool for understanding the neural mechanisms of how cognitive processes may deviate in clinical disorders, an important intermediary step towards improving translational psychiatry.
Tumor protein D52 (TPD52) affects cancer cell metabolism by negatively regulating AMPK
Authors: Chen Yali , Peng Changmin , Tan Wei , Yu Jia , Zayas Jacqueline , Peng Yihan , Lou Zhenkun , Pei Huadong , Wang Liewei
Published: March 2021

The AMP-activated protein kinase (AMPK) is a central regulator of energy homeostasis, with deregulation leading to cancer and other diseases. When intracellular ATP levels decrease during energy stress, AMPK is phosphorylated and activated through AMP binding. However, how this pathway is dysregulated in cancer remains unclear. Here, we find that tumor protein D52 (TPD52), initially identified to be overexpressed in many human cancers, forms a stable complex with AMPK in cancer cells. TPD52 directly interacts with AMPKα and inhibits AMPKα kinase activityin vitroandin vivo. We generated TPD52 transgenic mice, and found that overexpression of TPD52 leads to AMPK inhibition and multiple metabolic defects in mice. Together, our results shed new light on AMPK regulation and on our understanding of the etiology of cancers with TPD52 overexpression.
Trophic transfer of microplastics enhances plastic additive accumulation in fish
Authors: Hasegawa Takaaki , Mizukawa Kaoruko , Yeo Bee Geok , Sekioka Tomonori , Takada Hideshige , Nakaoka Masahiro
Published: March 2021

Organisms ingest microplastics directly from environments and indirectly from food sources. Ingesting microplastics can lead to an organism accumulating plastic-derived chemicals. However, the relative contributions of the two exposure routes (direct ingestion vs. indirect ingestion) to plastic-derived chemical accumulation in an organism are unknown. Using microplastics containing different types of plastic additives, we performed exposure experiments to compare chemical accumulation patterns in fish (Myoxocephalus brandti) between the exposure from the water and prey (Neomysisspp.). We found significantly higher brominated flame retardant concentrations in fish fed microplastic-contaminated prey than fish exposed to microplastics suspended in the water. The results indicate that prey-mediated ingestion of microplastics can be a more significant route for organisms accumulating plastic-derived chemicals, suggesting that organisms at higher trophic levels are more exposed to microplastics and associated chemicals than organisms at lower trophic levels.
Molecular mechanism underlying substrate recognition of the peptide macrocyclase PsnB
Authors: Song Inseok , Kim Younghyeon , Yu Jaeseung , Go Su Yong , Lee Hong Geun , Song Woon Ju , Kim Seokhee
Published: March 2021

Graspetides, also known as omega-ester-containing peptides (OEPs), are a family of ribosomally synthesized and post-translationally modified peptides (RiPPs) bearing side-to-side macrolactone or macrolactam linkages. Here we present molecular details of the precursor recognition of the macrocyclase enzyme PsnB in the biosynthesis of plesiocin, a Group 2 graspetide. Biochemical analysis revealed that, in contrast to other RiPPs, the core region of the plesiocin precursor peptide noticeably enhanced the enzyme-precursor interaction via the conserved glutamates. We obtained four crystal structures of symmetric or asymmetric PsnB dimers including those with a bound core peptide and a nucleotide, and suggest that the highly conserved Arg213 at the enzyme active site specifically recognizes a ring-forming acidic residue and escorts it to ATP for phosphorylation. Collectively, this study provides insights into the mechanism underlying substrate recognition in the graspetide biosynthesis, and lays a foundation for engineering new variants.
Psychomotor Impairments and Therapeutic Implications Revealed by a Mutation Associated with Infantile Parkinsonism-Dystonia
Authors: Aguilar Jenny I. , Cheng Mary Hongying , Font Josep , Schwartz Alexandra C. , Ledwitch Kaitlyn , Duran Amanda , Mabry Samuel J. , Belovich Andrea N. , Zhu Yanqi , Carter Angela M. , Shi Lei , Kurian Manju A. , Fenollar-Ferrer Cristina , Meiler Jens , Ryan Renae M. , Mchaourab Hassane S. , Bahar Ivet , Matthies Heinrich J. G. , Galli Aurelio
Published: March 2021

Parkinson disease (PD) is a progressive, neurodegenerative disorder affecting over 6.1 million people worldwide. Although the cause of PD remains unclear, studies of highly-penetrant mutations identified in early-onset familial parkinsonism have contributed to our understanding of the molecular mechanisms underlying disease pathology. Dopamine (DA) transporter (DAT) deficiency syndrome (DTDS) is a distinct type of infantile parkinsonism-dystonia that shares key clinical features with PD, including motor deficits (progressive bradykinesia, tremor, hypomimia) and altered DA neurotransmission. Here, we define structural, functional, and behavioral consequences of a Cys substitution at R445 in human DAT (hDAT R445C), identified in a patient with DTDS. We found that this R445 substitution disrupts a phylogenetically conserved intracellular (IC) network of interactions that compromise the hDAT IC gate. This is demonstrated by both Rosetta molecular modeling and fine-grained simulations using hDAT R445C, as well as EPR analysis and X-ray crystallography of the bacterial homolog leucine transporter. Notably, the disruption of this IC network of interactions supported a channel-like intermediate of hDAT and compromised hDAT function. We demonstrate thatDrosophila melanogasterexpressing hDAT R445C show impaired hDAT activity, which is associated with DA dysfunction in isolated brains and with abnormal behaviors monitored at high-speed time resolution.

We show that hDAT R445CDrosophilaexhibit motor deficits, lack of motor coordination (i.e. flight coordination) and phenotypic heterogeneity in these behaviors that is typically associated with DTDS and PD. These behaviors are linked with altered dopaminergic signaling stemming from loss of DA neurons and decreased DA availability. We rescued flight coordination through enhanced DAT surface expressionviathe lysosomal inhibitor chloroquine. Together, these studies shed light on how a DTDS-linked DAT mutation underlies DA dysfunction and, more broadly, the clinical phenotypes shared by DTDS and PD.
Structure and dynamics of the SARS-CoV-2 envelope protein monomer
Authors: Kuzmin Alexander , Orekhov Philipp , Astashkin Roman , Gordeliy Valentin , Gushchin Ivan
Published: March 2021

Coronaviruses, especially SARS-CoV-2, present an ongoing threat for human wellbeing. Consequently, elucidation of molecular determinants of their function and interaction with host is an important task. Whereas some of the coronaviral proteins are extensively characterized, others remain understudied. Here, we use molecular dynamics simulations to analyze the structure and dynamics of the SARS-CoV-2 envelope (E) protein (a viroporin) in the monomeric form. The protein consists of the hydrophobic α-helical transmembrane domain (TMD) and amphiphilic α-helices H2 and H3, connected by flexible linkers. We show that TMD has a preferable orientation in the membrane, while H2 and H3 reside at the membrane surface. Orientation of H2 is strongly influenced by palmitoylation of cysteines Cys40, Cys43 and Cys44. Glycosylation of Asn66 affects the orientation of H3. We also observe that the E protein both generates and senses the membrane curvature, preferably localizing with the C-terminus at the convex regions of the membrane. This may be favorable for assembly of the E protein oligomers, whereas induction of curvature may facilitate budding of the viral particles. The presented results may be helpful for better understanding of the function of coronaviral E protein and viroporins in general, and for overcoming the ongoing SARS-CoV-2 pandemic.
A role for glial fibrillary acidic protein (GFAP)-expressing cells in the regulation of gonadotropin-releasing hormone (GnRH) but not arcuate kisspeptin neuron output
Authors: Vanacker Charlotte , DeFazio R. Anthony , Sykes Charlene M. , Moenter Suzanne M.
Published: March 2021

GnRH neurons are the final central neural output regulating fertility. Kisspeptin neurons in the hypothalamic arcuate nucleus (KNDy neurons) are considered the main regulator of GnRH output. GnRH and KNDy neurons are surrounded by astrocytes, which can modulate neuronal activity and communicate over distances. Prostaglandin E2 (PGE2), synthesized primarily by astrocytes, increases GnRH neuron activity and downstream pituitary release of luteinizing hormone (LH). We hypothesized GFAP-expressing astrocytes play a role regulating GnRH and/or KNDy neuron activity and LH release. We used adenoassociated viruses to target designer receptor exclusively activated by designer drugs (DREADDs) to GFAP-expressing cells to activate Gq or Gi-mediated signaling. Activating Gq signaling in the preoptic area, near GnRH neurons, but not in the arcuate, increases LH releasein vivoand GnRH firingin vitrovia a mechanism in part dependent upon PGE2. These data suggest astrocytes can activate GnRH/LH release in a manner independent of KNDy neurons.
Five years of citizen science and standardized field surveys reveal a threatened urban Eden for wild bees in Brussels, Belgium
Authors: Vereecken Nicolas J. , Weekers Timothy , Marshall Leon , D’Haeseleer Jens , Cuypers Maarten , Vanormelingen Pieter , Pauly Alain , Pasau Bernard , Leclercq Nicolas , Tshibungu Alain , Molenberg Jean-Marc , De Greef Stéphane
Published: March 2021

Urbanisation is often put forward as an important driver of biodiversity loss, including for pollinators such as wild bees. However, recent evidence shows that the mosaics of urban green spaces, and in particular certain categories of informal urban green spaces (IGS), can play an important role to help native wild bees thrive in cities.

Here, we describe the results of five years of citizen science and standardised field surveys of wild bees conducted at the Friche Josaphat, a 24-ha urban wasteland in the Brussels-Capital Region (Belgium). These field surveys were initiated following the planned restructuring and partial destruction of this site by the regional authorities.

We recorded a total of 2,507 specimens belonging to 127 species of wild bees, i.e. 60.5% of the 210 species recorded regionally, including nine that are threatened with extinction at national or European scales. The Friche Josaphat encompasses a significant share of the functional and phylogenetic diversity of wild bees known from the Brussels-Capital Region and is one of the most species-rich localities known to date for wild bees in Belgium.

Collectively, our results highlight the strong complementarity of citizen science and academic approaches in biodiversity surveys, and they reaffirm that wastelands are essential components of urban biodiversity. Our study stresses the need to provide biodiverse IGS with a formal status within the mosaic of urban green spaces, but also to acknowledge and safeguard their natural capital and the multiple ecosystem services they provide.
Marketing bank services to financially vulnerable customers: evidence from an emerging economy
Authors: Mogaji Emmanuel , Adeola Ogechi , Hinson Robert Ebo , Nguyen Nguyen Phong , Nwoba Arinze Christian , Soetan Taiwo O.
Published: March 2021

Purpose

This study aims to explore how banks in Nigeria are marketing financial services to financially vulnerable customers.

Design/methodology/approach

A multiple case study research strategy was used to analyse three commercial banks and two microfinance banks. Data were collected using semi-structured interviews with the banks' directors as well as from banks' published annual reports and archival images.

Findings

The study reveals that Nigerian banks develop different product development portfolios, adopt innovative traditional marketing schemes and apply inclusive technologies to reach and extend services to the unbanked and financially vulnerable customers in the society.

Research limitations/implications

Banks should focus on consumer engagement through the proactive development of technologies and employ innovative marketing methods. Customers' banking experiences can be enhanced if banks communicate with and educate customers about technological modes of engagement. In addition, financial service transaction support and financial literacy education can assist banks in marketing their services to financially vulnerable customers, in mutually beneficial ways.

Originality/value

This study shows how financial service operators' market and extend their services to financially vulnerable customers in emerging markets. It empirically establishes the importance of financial services to financially excluded customers.
Development of research agenda on demonetization based on bibliometric visualization
Authors: Jain Deepa , Dash Manoj Kumar , Thakur Keshav Singh
Published: March 2021

Purpose

The purpose of present study is to identify influential aspects of published literature, research streams and future research questions to set forth future research agenda based on comprehensive literature review using bibliometric and content analysis.

Design/methodology/approach

The study analyzed 285 documents from the international Scopus database using bibliometric analysis and content analysis. VOSviewer software is used for bibliometric analysis.

Findings

The study identified influential aspects of published literature; identified five significant research streams: (1) Demonetization and financial system, (2) Demonetization and financial technology, (3) Demonetization and financial market, (4) Demonetization and digital payment system and (5) Demonetization and governance and proposed 27 key future research questions to develop future research agenda.

Practical implications

The present study makes significant contribution to the literature by providing a framework for future research. The framework provides opportunities to future researchers to explore the web of relations among five identified research streams as future research agenda.

Originality/value

The present work is unique in its way of contribution, as to the best of researchers' knowledge no work was witnessed in published literature to cover demonetization in a detailed and comprehensive manner. The present study fills this gap by conducting bibliometric analysis and content analysis. The study proposed conceptual framework for demonetization characterization to understand the demonetization literature well; and also proposed framework for future researcher to be explored further.
Situating race: the case for examining Black children’s informal mathematics learning outside of schools
Authors: Cunningham Jahneille , Gomez Kimberley
Published: March 2021

Purpose

The purpose of this paper is to highlight the ways racialization in K-12 mathematics classrooms has narrowed the understanding of mathematical learning for Black children.

Design/methodology/approach

Drawing on situated learning theory and funds of knowledge, the authors argue that the social learning context of mathematics classrooms has limited the understanding of what Black children are capable of mathematically. The authors suggest that as a community of practice, mathematics classrooms may be marginalizing Black children, as well as other students of color, by devaluing their community-based knowledge and ways of knowing.

Findings

The extant literature portrays Black children as struggling in mathematics; however, this research is overwhelmingly conducted based on school performance measures. Yet, if one looks beyond the classroom to Black children's homes and communities, a plethora of mathematical knowledge tied to cultural and community practices may be found. As such, Black children who struggle in mathematics classroom may be experiencing misalignment across contexts, rather than a lack of mathematical knowledge altogether.

Practical implications

This paper has implications for classroom practice, particularly teacher ideologies pertaining to community-based knowledge. The authors urge mathematics education researchers and practitioners to look beyond the classroom, as community-based mathematical practices may provide more insight into students’ mathematical capabilities. These implications are particularly important for educating students of color, who often experience a subpar classroom education.

Originality/value

In this paper, the authors provide a critical lens to situated learning theory, pushing mathematics education research to examine the underexplored topic of Black children's out-of-school mathematical practices.
Network orchestration: new role of business incubators?
Authors: Antunes Luiz Guilherme Rodrigues , de Castro Cleber Carvalho , Mineiro Andrea Ap da Costa
Published: March 2021

Purpose

The purpose of this paper is to analyze the performance of incubators in the stages of formation and development of incubated business networks, especially in bottom-up and top-down network models.

Design/methodology/approach

The research is defined as qualitative and descriptive, with the application of multiple case studies, in which two networks of incubated businesses were investigated, one being top-down and the other bottom-up, which emerged within the incubation process of two business incubators (CIETEC and INCIT). To make the study operational, 11 semi-structured interviews were carried out and the thematic analysis of content was developed.

Findings

The results pointed out that in the top-down network the incubator performs a new assignment, the network orchestration, which corresponds to the actions of formation, coordination and governance of the group. In the bottom-up network, it was found that the role of the incubator was to expand the value offers usually practiced.

Research limitations/implications

As a limitation of the research, the very limitation of case studies is pointed out that is they do not allow for generalizations.

Practical implications

The research contributes to reflections on the effectiveness of the incubator and sheds light on the complementarity of networks in incubation processes, providing gains for incubators, incubated businesses and society.

Originality/value

The originality of this document is the new role of the incubator, which is orchestration, and its categorization. The results allow us to understand the effects of providing networks and relationships for incubated businesses. In addition, this study broadens the focus of traditional analyses of the incubator–incubated duo to consider the incubator–network–incubated trio.
Does municipal fiscal distress hinder inter-municipal cooperation?
Authors: Bocchino Matteo , Padovani Emanuele
Published: March 2021

Purpose

Inter-municipal cooperation (IMC) has been increasingly adopted worldwide to tackle issues of size and cost reduction in the provision of public services. Although the determinants of cooperation among municipalities have been widely investigated in the prior literature, little is known about the link between a municipality's financial health and that of the supra-municipal entity formed under IMC. The purpose of this study is to fill this research gap by analyzing the case of municipal unions (MUs) in Italy.

Design/methodology/approach

A quantitative approach has been used, applying OLS and quantile regression on financial information and other variables of municipalities and their MUs.

Findings

The study finds that the most important condition of operation for IMC, that is, financial sustainability, is directly linked to the financial health of member municipalities and the functional integration reached with the supra-municipal entity.

Originality/value

The study analyses all MUs in Italy, focusing on the factors affecting their financial sustainability. In doing so, it sheds light on the factors that influence the financial sustainability of second-tier governments, which rely on external funding.
The digital skills divide: evidence from the European tourism industry
Authors: Carlisle Sheena , Ivanov Stanislav , Dijkmans Corné
Published: March 2021

Purpose

This paper aims to present the findings from a European study on the digital skills gaps in tourism and hospitality companies.

Design/methodology/approach

Mixed methods research was adopted. The sample includes 1,668 respondents (1,404 survey respondents and 264 interviewees) in 5 tourism sectors (accommodation establishments, tour operators and travel agents, food and beverage, visitor attractions and destination management organisations) in 8 European countries (UK, Italy, Ireland, Spain, Hungary, Germany, the Netherlands and Bulgaria).

Findings

The most important future digital skills include online marketing and communication skills, social media skills, MS Office skills, operating systems use skills and skills to monitor online reviews. The largest gaps between the current and the future skill levels were identified for artificial intelligence and robotics skills and augmented reality and virtual reality skills, but these skills, together with computer programming skills, were considered also as the least important digital skills. Three clusters were identified on the basis of their reported gaps between the current level and the future needs of digital skills. The country of registration, sector and size shape respondents’ answers regarding the current and future skills levels and the skills gap between them.

Originality/value

The paper discusses the digital skills gap of tourism and hospitality employees and identifies the most important digital skills they would need in the future.
Authenticity and employee wellbeing with reference to emotional work: a review
Authors: Mehta Poonam
Published: March 2021

Purpose

In the service industry, there is an involvement of the human factor which comprises continuous interpersonal interactions. Sometimes, these interactions create incongruence between displayed and felt emotions which distract the employees from their authentic self and impair their well-being. This paper aims to made an attempt to review different studies to identify an association between authenticity at the workplace and employee well-being with reference to emotional work.

Design/methodology/approach

The different studies have been reviewed mentioning the association between authenticity at the workplace and employee well-being with reference to emotional work published during the period of 1983–2020. The database which is used to identify and extract the research papers includes APA PycNET, Business Perspectives, Elsevier, Emerald Insight, Inderscience Publishers, SAGE, Taylor and Francis, etc. The keywords used for shortlisting the studies include employee well-being, emotional work, emotional dissonance, job satisfaction, surface acting, authenticity, burnout, authentic living, self-alienation.

Findings

The study has determined that emotional work influences the authenticity of an employee which further impacts the well-being of employees.

Research limitations/implications

The present review would aid the researchers in explaining the relevance of authenticity at the workplace for enhancing the employee well-being specifically in emotional work settings.

Social implications

Promoting well-being at the workplace requires an action-oriented approach from the national level also. Hence, the present study may help in drawing inferences for framing well-being policies for employees at the national level.

Originality/value

The paper is amongst the few reviews which have analysed the substantial role of authenticity in the context of emotional work to improve employee well-being.
The use of simulation in occupational therapy education: A scoping review
Authors: Grant Terri , Thomas Yvonne , Gossman Peter , Berragan Liz
Published: March 2021

Introduction

Simulated learning experiences are a common feature of many health professions’ pre‐registration curricula. However, the use of simulation within occupational therapy is still largely undefined. This scoping review seeks to identify and summarise the available evidence exploring the use of simulation within occupational therapy pre‐registration education.

Methods

A search was conducted in four databases for articles published between 2009 and 2020 to identify international literature relevant to the use of simulation within occupational therapy education. Articles were evaluated using the appropriate Critical Appraisal Skills Programme (CASP) tool and key features and benefits of current simulation education were identified using thematic analysis.

Results

A total of 32 papers were included within the review. Four themes were identified and explored: simulation methods, authenticity, global approaches to simulation, and relationship to practice education.

Conclusion

Simulation is taking place in many different forms within occupational therapy internationally. It is positively received by students and may provide an effective replacement for practice education if focussed on professional standards and competencies. Further research into the potential effectiveness of simulation in relation to practice learning is indicated.
Financial `metrics for comparing Australian retirement villages
Authors: Kyng Timothy , Pitt David , Purcal Sachi , Zhang Jinhui
Published: March 2021

Retirement village contracts are complex, blending together financial options on real estate, life annuities and life insurance. We analyse the structure of the cash flows involved in a retirement village contract and distil the cost components into an equivalent monthly comparison rent. In general, we observe lower monthly rents when the maintenance fees and deferred management fees are lower, when higher rates of capital gain are evident, and, importantly, when retirees reside in the retirement village for a longer period. Our analysis provides a framework to meaningfully compare the relative merits of the finances incorporated into retirement village contracts.
Does positive CSR increase willingness to invest in a company based on performance? The incremental role of combined assurance
Authors: Phang Soon‐Yeow , Hoang Hien
Published: March 2021

We examine whether the communication of combined assurance is effective in increasing favourable investment decisions towards a company with negative financial performance. We find that the communication of combined assurance, compared to when only corporate social responsibility (CSR) assurance is communicated, results in a more significant impact on investors’ decisions to invest when the company has negative performance, but this effect is less significant when the company has positive performance. When the company has positive performance, perceived reliability and willingness to invest do not change regardless of whether combined assurance is included or not.
The effectiveness of using e‐cigarettes for quitting smoking compared to other cessation methods among adults in the United Kingdom
Authors: McDermott Máirtín S. , East Katherine A. , Brose Leonie S. , McNeill Ann , Hitchman Sara C. , Partos Timea R.
Published: March 2021

Background and aims

Evidence on the effectiveness of electronic cigarettes (ECs) to facilitate abstinence from smoking is limited. The current study aimed to estimate the relative effectiveness of ECs and smoking cessation medication compared with using no help, accounting for frequency of use of ECs.

Design

Four consecutive wave‐to‐wave transitions (waves 1–2, 2–3, 3–4 or 4–5) of a longitudinal online survey collected between 2012 and 2017 were analysed. Time between waves ranged between 12 and 17 months. Cigarette smokers at the baseline wave who attempted to quit smoking between waves were included.

Setting

United Kingdom

Participants

A total of 1155 respondents (aged 18–81, 56.1% male, 64.6% in social grade C2DE, 93.8% white) provided 1580 pairs of observations for the primary analysis.

Measurements

Primary outcome: abstinence from smoking for at least 1 month at follow‐up; secondary outcome: at least 1 month's abstinence from smoking between baseline and follow‐up. The main predictor was stop smoking aid used (No help, nicotine replacement therapy only, smoking cessation medication only, disposable/cartridge EC, refill/modular EC, combination), adjusted for demographics.

Findings

Primary Compared with using no help, the odds of abstinence were increased by daily use of disposable/cartridge ECs (OR = 3.31 (1.32, 8.26), P = .010) and daily use of refill/modular ECs (OR = 5.47 (2.70, 11.11), P < .001). Odds were reduced by non‐daily use of disposable/cartridge ECs (OR = 0.23 (0.08–0.63), P = .005), and by use of disposable/cartridge ECs to quit and no longer using at follow‐up (OR = 0.10 (0.16–0.62), P < .013). Secondary Results were similar to the primary outcome; however, odds of abstinence were also increased by use of smoking cessation medication (OR = 4.15 (1.79, 9.62), P = .001).

Conclusions

When used daily, electronic cigarettes appear to facilitate abstinence from smoking when compared with using no help.
Management of repository corticotropin injection therapy for non‐infectious uveitis: a Delphi study
Authors: Nguyen Quan Dong , Anesi Stephen D. , Chexal Saradha , Chu David S. , Dayani Pouya N. , Leng Theodore , Meleth Annal D. , Sallam Ahmed A. , Sheppard John D. , Silverstein Steven M. , Toyos Melissa , Wang Robert C. , Foster Charles Stephen
Published: March 2021

Purpose

Diagnosis and management of non‐infectious uveitis (NIU), a major cause of blindness worldwide, are challenging. Corticosteroids, the cornerstone of therapy, are not appropriate for long‐term use, and while non‐biologic and biologic immunomodulators may be used for some patients, data on their efficacy and safety in this population are limited. Repository corticotropin injection (RCI), believed to affect uveitis by multiple mechanisms, has received regulatory approval for treatment of ophthalmic diseases including posterior uveitis, but is not widely used or discussed in guidelines for the management of uveitis and ocular inflammatory diseases.

Methods

The index study employed a modified Delphi process with a panel of 14 US‐based ophthalmologists. Consensus recommendations were developed through a series of three questionnaires. Panellists rated statements on a Likert scale from –5 (strongly disagree) to +5 (strongly agree).

Results

The Delphi panel provided consensus recommendations on examinations and testing needed for diagnosis, treatment goals, and the use of corticosteroids, as well as the use of non‐biologic and biologic immunomodulators. The panel reached consensus that RCI may be considered for posterior and pan‐uveitis, and dosing should be individualized for each patient. Dose reduction/discontinuation should be considered for excessive RCI‐related toxicity, hyperglycaemia and/or diabetic complications, excessive costs, or remission ≥ 2 years. Patients should be weaned from RCI if uveitis is stable and well controlled. Adverse events during RCI therapy can be managed by appropriate interventions, with dose reduction/discontinuation considered if events are severe or recurrent.

Conclusions

Expert consensus suggests RCI may be an appropriate treatment option for some patients with uveitis when other therapies are ineffective or intolerable.
Clinicopathological characterisation of myeloproliferative neoplasm‐unclassifiable (MPN‐U): a retrospective analysis from a large UK tertiary referral centre
Authors: Deschamps Paul , Moonim Mufaddal , Radia Deepti , Curto‐Garcia Natalia , Woodley Claire , Bassiony Sarah , O'Sullivan Jennifer , Harrington Patrick , Raj Kavita , Francis Yvonne , Kordasti Shahram , Ali Sahra , Harrison Claire N. , McLornan Donal P.
Published: March 2021

Myeloproliferative neoplasm‐unclassifiable (MPN‐U) presents an MPN‐type phenotype that fails to meet diagnostic criteria for other MPN variants. Variability in the clinicopathological phenotypes presents many challenges. Amongst a registry cohort of 1512 patients with MPN, 82 with MPN‐U were included, with a median (range) age of 49·7 (13–79) years. Albeit heterogeneous, common presentation features included raised lactate dehydrogenase, thrombocytosis and clustered/pleomorphic megakaryocytes on trephine biopsy. Thrombosis was common (21%), necessitating vigilance. The median event‐free survival was 11·25 years (95% confidence interval 9·3–not reached), significantly shortened in cases with lower platelet counts (<500 × 109/l) and a leucocytosis (≥12 × 109/l) at presentation. Generation of potential MPN‐U prognostic scores is required.
Rising incidence rates and unaltered survival rates for primary upper urinary tract urothelial carcinoma: a Dutch population‐based study from 1993 to 2017
Authors: van Doeveren Thomas , van der Mark Marianne , van Leeuwen Pim J. , Boormans Joost L. , Aben Katja K.H.
Published: March 2021

Aim

To assess trends in the incidence, disease management and survival rates for upper urinary tract urothelial carcinoma (UTUC) in the Netherlands.

Materials and methods

Patients diagnosed with primary UTUC in the Netherlands between 1993 and 2017 were identified through the population‐based Netherlands Cancer Registry (NCR). Patient and tumour characteristics, as well as information on treatment and vital status, were retrieved from the NCR. Age‐standardized incidence rates were calculated, stratified by age, gender, calendar period and disease stage. Relative survival served as an approximation for cancer‐specific survival.

Results

We identified 13 314 patients with primary UTUC. The age‐standardized incidence rate increased from 2.0 in 1993 to 3.2 per 100 000 person‐years in 2017, without change in gender distribution. The increase in incidence held for all disease stages except organ‐confined (T1–T2) disease. The most prominent increase was in superficial (Tis/Ta) and metastatic (M+) UTUC, which increased from 0.6 to 1.2 and 0.1 to 0.4 per 100 000 person‐years, respectively. The 5‐year relative survival did not change over time: 57.0% (95% confidence interval 55.9–58.1). Applied treatments were largely the same over the study period, although fewer radical nephroureterectomies and more kidney‐sparing surgeries were performed in the most recent years. The use of peri‐operative intravesical chemotherapy modestly increased.

Conclusion

Between 1993 and 2017, the age‐standardized incidence of primary UTUC in the Netherlands has increased by more than 50%, but the relative survival of UTUC patients remained unchanged. Preventive measures against exposure to risk factors, early detection of disease, and more efficacious treatment methods are needed to improve outcomes of patients with UTUC.
Short‐chain fatty acids and bile acids in human faeces are associated with the intestinal cholesterol conversion status
Authors: Matysik Silke , Krautbauer Sabrina , Liebisch Gerhard , Schött Hans‐Frieder , Kjølbæk Louise , Astrup Arne , Blachier Francois , Beaumont Martin , Nieuwdorp Max , Hartstra Annick , Rampelli Simone , Pagotto Uberto , Iozzo Patricia
Published: March 2021

Background and Purpose

The analysis of human faecal metabolites can provide an insight into metabolic interactions between gut microbiota and the host organism. The creation of metabolic profiles in faeces has received little attention until now, and reference values, especially in the context of dietary and therapeutic interventions, are missing. Exposure to xenobiotics significantly affects the physiology of the microbiome, and microbiota manipulation and short‐chain fatty acid administration have been proposed as treatment targets for several diseases. The aim of the present study is to give concomitant concentration ranges of faecal sterol species, bile acids and short‐chain fatty acids, based on a large cohort.

Experimental Approach

Sterol species, bile acids and short‐chain fatty acids in human faeces from 165 study participants were quantified by LC–MS/MS. For standardization, we refer all values to dry weight of faeces. Based on the individual intestinal sterol conversion, we classified participants into low and high converters according to their coprostanol/cholesterol ratio.

Key Results

Low converters excrete more straight‐chain fatty acids and bile acids than high converters; 5th and 95th percentile and median of bile acids and short‐chain fatty acids were calculated for both groups.

Conclusion and Implications

We give concentration ranges for 16 faecal metabolites that can serve as reference values. Patient stratification into high or low sterol converter groups is associated with significant differences in faecal metabolites with biological activities. Such stratification should then allow better assessment of faecal metabolites before therapeutic interventions.

LINKED ARTICLES

This article is part of a themed issue on Oxysterols, Lifelong Health and Therapeutics. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.16/issuetoc
COVID‐19 test result reporting for deceased donors: Emergent policies, logistical challenges, and future directions
Authors: Lentine Krista L. , Singh Neeraj , Woodside Kenneth J. , Schnitzler Mark A. , Li Ruixin , Alhamad Tarek , Rothweiler Richard , Parsons Ronald F. , Mannon Roslyn B. , Snyder Jon , Cooper Matthew , Axelrod David A.
Published: March 2021

The coronavirus disease 2019 (COVID‐19) pandemic poses unprecedented challenges to the transplant community, including organ procurement organizations (OPOs), transplant centers, regulatory agencies, and recipient candidates. Access to timely, accurate information on the status of deceased donor viral infection is essential in determining organ acceptance. The Organ Procurement and Transplantation Network expeditiously added fields to collect these data; however, use of the data collection fields was not uniform nationally. Standardized, field‐defined data capture and reporting are vital to ensure optimal organ utilization during this pandemic, and to prepare the community for subsequent challenges.