bluuebunny/crossref_metadata_2025 huggingface dataset:
Parasite genetic variation and systemic immune responses are not associated with different clinical presentations of cutaneous leishmaniasis caused by Leishmania aethiopica
Authors: Yizengaw Endalew , Takele Yegnasew , Franssen Susanne U. , Gashaw Bizuayehu , Yimer Mulat , Adem Emebet , Nibret Endalkachew , Yismaw Gizachew , Cruz Cervera Edward , Ejigu Kefale , Tamiru Dessalegn , Munshea Abaineh , Muller Ingrid , Weller Richard , Cotton James , Kropf Pascale
Published: April 2024

Cutaneous leishmaniasis (CL) is a neglected tropical skin disease, caused by the protozoan parasite Leishmania (L.). It is endemic to 90 countries and causes >200,000 new infections each year. In Ethiopia, CL is mainly caused by L. aethiopica and can present in different clinical forms: localised cutaneous leishmaniasis (LCL); mucocutaneous leishmaniasis (MCL), where the mucosa of the nose and/or the mouth are affected; and diffuse CL (DCL), characterised by non-ulcerating nodules. Persistent forms of LCL, as well as MCL and DCL, require treatment but are difficult to treat successfully and can lead to permanent disfigurement, social stigmatisation, and a mental health burden. The mechanisms behind the development of these different presentations of CL are not clearly understood, and both parasite and host factors could be involved. Here we analysed the whole genome sequence data for 48 clinical parasite isolates and show that parasites from CL cases with different presentations in a single Ethiopian setting are from the same genetic population. Furthermore, we did not identify any individual genetic variants significantly associated with disease presentation. We also measured plasma chemokine and cytokine levels of 129 CL patients presenting with different forms of CL. None of the cytokine or chemokine levels measured were significantly different between the different clinical presentations of CL. We also compared those with healthy nonendemic controls: our results show a chemokine but not a cytokine immune signature in patients with CL as compared to healthy nonendemic controls.
Ubiquitylation of nucleic acids by DELTEX ubiquitin E3 ligase DTX3L
Authors: Zhu Kang , Chatrin Chatrin , Suskiewicz Marcin J , Aucagne Vincent , Ahel Dragana , Ahel Ivan
Published: April 2024

Recent discoveries expanding the spectrum of ubiquitylation substrates to include non-proteinaceous molecules have broadened our understanding of this modification beyond conventional protein targets. However, the existence of additional types of substrates remains elusive. Here, we present evidence that nucleic acids can also be directly ubiquitylated. DTX3L, a member of the DELTEX family E3 ubiquitin ligases, ubiquitylates DNA and RNAin vitroand that this activity is not shared with another DELTEX family member DTX2. DTX3L shows preference for the 3’-terminal adenosine over other nucleotides. In addition, we demonstrate that ubiquitylation of nucleic acids is reversible by DUBs such as USP2 and SARS-CoV-2 PLpro. Overall, our study provides evidence for reversible ubiquitylation of nucleic acidsin vitroand discusses its potential functional implications.
Phase separation of a microtubule plus-end tracking protein into a fluid fractal network
Authors: Czub Mateusz P. , Uliana Federico , Grubić Tarik , Padeste Celestino , Rosowski Kathryn A. , Dufresne Eric R. , Menzel Andreas , Vakonakis Ioannis , Gasser Urs , Steinmetz Michel O.
Published: April 2024

Microtubule plus-end tracking proteins (+TIPs) are involved in virtually all microtubule-based cellular processes, and it has been recently proposed that they function as liquid condensates. However, the formation process and internal organization of +TIP condensates are poorly understood. Here, we have investigated the phase separation of the CLIP-170 family member Bik1, a key +TIP implicated in budding yeast cell division. We found that Bik1 is a rod-shaped dimer whose conformation is dominated by its central coiled-coil domain. Liquid condensation is accompanied by Bik1 conformational rearrangements, leading to a 2-3-fold rise in interactions between the protein’s folded and disordered domains. In contrast to classical liquids, the supramolecular structure of the Bik1 condensate is heterogeneous, with a fractal structure of protein-rich and protein-free domains. This observation provides structural evidence in support of recent models of biomolecular condensates based on percolation. More broadly, our results provide insights into the structure, dynamic rearrangement, and organization of a complex, multidomain protein in its dilute and condensed phases. Our experimental framework can be extended to other biomolecular condensates, including more intricate +TIP networks.
Dramatic reduction in trypanosome motility occurs without large-scale changes to paraflagellar rod ultrastructure
Authors: Gabriel Heloisa B , Kelly Ruby , Moreira-Leite Flavia , Sunter Jack D
Published: April 2024

Eukaryotic flagella - widely conserved structures involved in signalling, metabolism and motility – have a core microtubular axoneme that, in many organisms, is accompanied by prominent extra-axonemal structures. In kinetoplastids, including human parasites such as trypanosomes andLeishmania, a dense filamentous lattice called the paraflagellar rod (PFR) accompanies the axoneme for most of its length. While functional studies showed that the presence of the core PFR structure is required for normal motility, the evaluation of more subtle roles for the PFR in motility has been hampered by limited functional and localisation data, particularly on components not essential to form the ‘core’ PFR, such as signalling and metabolism proteins. Here, we addressed these issues by using the genome-wide protein localisation database TrypTag to define a PFR proteome, which was used as a base for a subtler analysis of PFR structure and function. We combined the localisation of fluorescently tagged PFR proteins relative to other cellular components with electron microscopy data on the PFR ultrastructure to localise 81 proteins to specific subdomains of the PFR. Functional analysis of a subset of PFR proteins by gene deletion and RNAi demonstrated that a novel PFR component (PFC21) is required for correct assembly of the outer PFR domain. Importantly, in some single deletion mutants, cell motility was impaired without gross disruption to the core PFR ultrastructure. Thus, our study shows that the PFR has subtle, likely regulatory roles in motility unrelated to any physical constraints that the ‘bulky’ PFR structure may impose on flagella function.
Parallel evolution at the regulatory base-pair level contributes to mammalian inter-specific differences in polygenic traits.
Authors: Okamoto Alexander Shumpei , Capellini Terence D
Published: April 2024

Parallel evolution occurs when distinct lineages with similar ancestral states converge on a new phenotype. Parallel evolution has been well documented at the organ, gene pathway, and amino-acid sequence level but in theory it can also occur at individual nucleotides within non-coding regions. To examine the role of parallel evolution in shaping the biology of mammalian complex traits, we used data on single nucleotide polymorphisms (SNPs) influencing human intraspecific variation to predict trait values in other species for eleven complex traits. We found that the alleles at SNP positions associated with human intraspecific height and red blood cell count variation are associated with interspecific variation in the corresponding traits across mammals. These associations hold for deeper branches of mammalian evolution as well as between strains of collaborative cross mice. While variation in red blood cell count between primates uses both ancient and more recently evolved genomic regions, we found that only primate-specific elements were correlated with primate body size. We show that the SNP positions driving these signals are flanked by conserved sequences, maintain synteny with target genes, and overlap transcription factor binding sites. This work highlights the potential of conserved but tunable regulatory elements to be reused in parallel to facilitate evolutionary adaptation in mammals.
PAbFold: Linear Antibody Epitope Prediction using AlphaFold2
Authors: DeRoo Jacob , Terry James S. , Zhao Ning , Stasevich Timothy J. , Snow Christopher D. , Geiss Brian J.
Published: April 2024

Defining the binding epitopes of antibodies is essential for understanding how they bind to their antigens and perform their molecular functions. However, while determining linear epitopes of monoclonal antibodies can be accomplished utilizing well-established empirical procedures, these approaches are generally labor- and time-intensive and costly. To take advantage of the recent advances in protein structure prediction algorithms available to the scientific community, we developed a calculation pipeline based on the localColabFold implementation of AlphaFold2 that can predict linear antibody epitopes by predicting the structure of the complex between antibody heavy and light chains and target peptide sequences derived from antigens. We found that this AlphaFold2 pipeline, which we call PAbFold, was able to accurately flag known epitope sequences for several well-known antibody targets (HA / Myc) when the target sequence was broken into small overlapping linear peptides and antibody complementarity determining regions (CDRs) were grafted onto several different antibody framework regions in the single-chain antibody fragment (scFv) format. To determine if this pipeline was able to identify the epitope of a novel antibody with no structural information publicly available, we determined the epitope of a novel anti-SARS-CoV-2 nucleocapsid targeted antibody using our method and then experimentally validated our computational results using peptide competition ELISA assays. These results indicate that the AlphaFold2-based PAbFold pipeline we developed is capable of accurately identifying linear antibody epitopes in a short time using just antibody and target protein sequences. This emergent capability of the method is sensitive to methodological details such as peptide length, AlphaFold2 neural network versions, and multiple-sequence alignment database. PAbFold is available athttps://github.com/jbderoo/PAbFold.
Timing-dependent effects of elevated maternal glucocorticoids on offspring brain gene expression in a wild small mammal
Authors: Westrick Sarah E. , Fischer Eva K. , van Kesteren Freya , Boutin Stan , Lane Jeffrey E. , McAdam Andrew G. , Dantzer Ben
Published: April 2024

An increase in maternal stress during offspring development can have cascading, life-long impacts on offspring behavior and physiology, which can vary depending on the timing of exposure to the stressor. By responding to stressors through increasing production of glucocorticoids (GCs), the hypothalamic-pituitary-adrenal (HPA) axis is a key mediator of maternal effects – both on the side of the mother and the offspring. At a molecular level, maternal effects are thought to be mediated through modifying transcription of genes, particularly in the brain. To better understand the evolutionary implications of maternal effects, more studies are needed on mechanisms of maternal effects in wild populations. To test how the timing of maternal stress impacts gene expression in the brains of offspring, we treated free-ranging North American red squirrels (Tamiasciurus hudsonicus) with GCs during late pregnancy or early lactation and collected brains from offspring around weaning. We used RNA-sequencing to measure gene expression in the hypothalamus and hippocampus. We found small differences in gene expression between GC-treated and control individuals suggesting long-term effects of the GC treatment on neural gene transcription. The general patterns of gene regulation across the transcriptome were consistent between the pregnancy and lactation-treated individuals. However, the number of significantly differentially expressed genes was higher in the lactation treatment group. These results support the idea that maternal stress affects neural gene expression in offspring, and these effects are dependent on timing. Our findings add valuable insight into the impact of maternal hormones on neural transcriptomics in a wild population.
Peer effects in internationalization of engineering enterprises: moderating analyses and heterogeneity tests
Authors: Niu Yanliang , Dai Chang , Zhang Renjie , Yao Hongjiang
Published: April 2024

Purpose

This study is devoted to examining the peer effects of engineering enterprises’ internationalization from the viewpoint of industry subdivision and how information and competition alter peer effects. Furthermore, the heterogeneity of peer effects is analyzed based on manager characteristics.

Design/methodology/approach

In this study, multiple regression analysis was conducted on a sample of 38 Chinese engineering enterprises listed in the Engineering News-Record’s top 250 international contractors over the period of 2013–2021. This study collected the paired data from the enterprise annual reports and the China Stock Market & Accounting Research database.

Findings

The results reveal that (1) there exist peer effects within the subdivided industry of the engineering field; the quality of information disclosure of peer enterprises and degree of market competition moderate the peer effects; (2) the peer effects of internationalization are more pronounced in engineering enterprises with managers who have lower ability, hold greater power or are older.

Practical implications

The findings of this study contribute to understanding the peer effect in the process of internationalization of engineering enterprises, and help enterprises to effectively supervise the irrational behavior of top managers, so as to develop better internationalization strategies.

Originality/value

The results extend peer effects to the subdivision industry of the engineering field. Furthermore, this study also enriches the relevant research on peer effects among enterprises by empirically supporting the moderating role of information and competition as well as analyzing the heterogeneity of the peer effects from the perspective of manager characteristics.
Perception of home teleworking during COVID-19 crisis in Spain: significant factors and assymetrical influence on acceptance and resistance
Authors: de Andres-Sanchez Jorge , Belzunegui-Eraso Angel , Erro-Garcés Amaya
Published: April 2024

Purpose

This paper aims to shed light on the perception of the consequences of implementing home teleworking (TW) for employers and employees amid the pandemic. By doing so, the research analyzes the factors that explain employers' and employees' perceptions of home TW and the symmetry of their impact on its acceptance and rejection.

Design/methodology/approach

The analysis is done over the survey “Trends in the digital society during SARS-COV-2 crisis in Spain” by the Spanish “Centro de Investigaciones Sociológicas.” The explanatory variables were selected and classified using the well-known taxonomy of Baruch and Nicholson (i.e. individual factors, family/home, organizational and job-related).

Findings

The global judgment of HTW is positive, but factors such as gender, age, children in care or being an employer nuance that perception. While some factors, such as the attitude of employees toward information communication technologies (ICTs), perceived productivity or the distance from home to work, have a significant link with both positive and negative perceptions of HTW, other factors can only explain either positive or negative perceptions. Likewise, the authors observed that being female and having children on care had a detrimental influence on opinions about HTW.

Practical implications

A clearer regulation of TW is needed to prevent imbalances in rights and obligations between companies and employees. The authors also highlight the potentially favorable effects of telecommuting on mitigating depopulation in rural areas.

Originality/value

The authors have also measured not only the significance of assessed factors on the overall judgment of HTW for firms and workers but also whether these factors impact acceptance and resistance attitudes toward TW symmetrically.
The effect of relational embeddedness on transparency in supply chain networks: the moderating role of digitalization
Authors: Feng Bo , Zheng Manfei , Shen Yi
Published: April 2024

Purpose

An emerging body of literature has pinpointed the role of supply chain structure in influencing the extent to which supply chain members disclose information about their internal practices and performance. Nevertheless, empirical research investigating the effects of firm-level relational embeddedness on network-level transparency still lags. Drawing on social network analysis, this research examines the effect of relational embeddedness on supply chain transparency and the contingent role of digitalization in the context of environmental, social and governance (ESG) information disclosure.

Design/methodology/approach

In their empirical analysis, the authors collected secondary data from the Bloomberg database about 2,229 firms and 14,007 ties organized in 107 extended supply chains. The authors employed supplier and customer concentration metrics to measure relational embeddedness and performed multiple econometric models to test the hypothesis.

Findings

The authors found a positive effect of supplier concentration on supply chain transparency, but the effect of customer concentration was not significant. Additionally, the digitalization of focal firms reinforced the impact of supplier concentration on supply chain transparency.

Originality/value

The study findings contribute by underscoring the critical effect of relational embeddedness on supply chain transparency, extending prior literature on social network analysis, providing compelling evidence for the intersection of digitalization and supply chain management, and drawing important implications for practices.
Do investors care about greening in corporations? The role of eco-innovation and CSR committee
Authors: Karaman Abdullah S. , Uyar Ali , Boussaada Rim , Karmani Majdi
Published: April 2024

Purpose

Prior studies mostly tested the association between carbon emissions and firm value in certain contexts. This study aims to advance the existing literature by concentrating on three indicators of greening in corporations namely resource use, emissions and eco-innovation, and examining their value relevance in the stock market at the global level. Furthermore, we deepen the investigation by exploring the moderating role of eco-innovation and the CSR committee between greening in corporations and market value.

Design/methodology/approach

The data for the study were retrieved from the Thomson Reuters Eikon database for the years between 2002 and 2019 and contain 17,961 firm-year observations which are analyzed through fixed-effects regression.

Findings

The results reveal that while resource usage is viewed as value-relevant by the market, the emissions and eco-innovation are not. However, despite eco-innovation per se not being value-relevant, its interaction with resource usage and emissions is value-relevant. Furthermore, CSR committees undertake a very critical role in translating greening practices into market value.

Research limitations/implications

While the results for emissions support the cost-concerned school, the findings for resource usage confirm the value creation school. Furthermore, the interaction effect of eco-innovation and CSR committee confirms the resource-based theory and stakeholder theory, respectively.

Practical implications

Investors regard eco-innovation-induced pro-environmental behaviors as value-relevant. These results propose firms replace eco-innovation at the focal point in developing environmental strategies and connecting other greening efforts to it. Moreover, CSR committees are critical to corporations in translating greening practices into firm value by developing and implementing disclosure and communication strategies.

Originality/value

The study’s originality stems from investigating the synergetic effect that eco-innovation and CSR committees generate in translating greening practices to greater market value at a global scale.
Vulnerability of Nigerian maize traders to a confluence of climate, violence, disease and cost shocks
Authors: Vargas Carolina M. , Liverpool-Tasie Lenis Saweda O. , Reardon Thomas
Published: April 2024

Purpose

We study five exogenous shocks: climate, violence, price hikes, spoilage and the COVID-19 lockdown. We analyze the association between these shocks and trader characteristics, reflecting trader vulnerability.

Design/methodology/approach

Using primary survey data on 1,100 Nigerian maize traders for 2021 (controlling for shocks in 2017), we use probit models to estimate the probabilities of experiencing climate, violence, disease and cost shocks associated with trader characteristics (gender, size and region) and to estimate the probability of vulnerability (experiencing severe impacts).

Findings

Traders are prone to experiencing more than one shock, which increases the intensity of the shocks. Price shocks are often accompanied by violence, climate and COVID-19 shocks. The poorer northern region is disproportionately affected by shocks. Northern traders experience more price shocks while Southern traders are more affected by violence shocks given their dependence on long supply chains from the north for their maize. Female traders are more likely to experience violent events than men who tend to be more exposed to climate shocks.

Research limitations/implications

The data only permit analysis of the general degree of impact of a shock rather than quantifying lost income.

Originality/value

This paper is the first to analyze the incidence of multiple shocks on grain traders and the unequal distribution of negative impacts. It is the first such in Africa based on a large sample of grain traders from a primary survey.
What is action ethnography? Reconsidering our intentions for impact in ethnographic practice
Authors: Vincett Joanne
Published: April 2024

Purpose

The purpose of this paper is to offer an accessible and interdisciplinary research strategy in organisational ethnography, called action ethnography, that acknowledges key concepts from action research and engaged and immersive ethnography. It aims to encourage methodological innovation and an impact turn in ethnographic practice.

Design/methodology/approach

A working definition of “action ethnography” is provided first. Then, to illustrate how an action ethnography can be designed by considering impact from the outset, the author draws on a study she is undertaking with a grassroots human rights monitoring group, based in England, and then discusses advantages and limitations to the approach.

Findings

The author suggests three main tenets to action ethnography that embrace synergies between action research and ethnography: researcher immersion, intervention leading to change and knowledge contributions that are useful to both practitioners and researchers.

Practical implications

This paper provides researchers who align with aspects of both action research and ethnography with an accessible research strategy to employ, and a better understanding of the interplay between the two approaches when justifying their research designs. It also offers an example of designing an action ethnography in practice.

Originality/value

Whereas “traditional” ethnography has emphasised a contribution to theoretical knowledge, less attention has been on a contribution to practice and to those who ethnographers engage with in the field. Action ethnography challenges researchers to consider the impact of their research from the outset during the research design, rather upon reflection after a study is completed.
Toward sustainable healthcare: linking environmental governance, business innovation and carbon emission in Europe
Authors: Al Amosh Hamzeh , Khatib Saleh F.A.
Published: April 2024

Purpose

Climate change is one of our time’s most pressing global environmental challenges, and environmental innovation is critical to addressing it. This study aims to investigate the relationship between environmental innovation and carbon emission in the healthcare industry in Europe while also examining the moderating role of environmental governance.

Design/methodology/approach

Data for this study were collected from publicly listed healthcare companies in ten European countries spanning the years 2012–2021. The selected countries encompassed Belgium, Denmark, France, Germany, Italy, Netherlands, Spain, Sweden, Switzerland and the United Kingdom. The research encompassed all healthcare companies for which data were accessible, resulting in a comprehensive dataset comprising 1,210 companies. The authors collected data from multiple sources, including annual reports, the World Bank and Eikon databases, to ensure a robust and extensive dataset.

Findings

The results of this study indicate that environmental governance plays a significant moderating role in the relationship between environmental innovation and carbon emission within the healthcare sector in Europe, but when combined with high levels of environmental innovation, strong environmental governance leads to enhanced efforts to reduce carbon emissions. This combination also contributes to meeting the expectations of a broader range of stakeholders and maintaining legitimacy.

Practical implications

The study’s findings have practical implications for healthcare regulators, policymakers and various stakeholders. It underscores the importance of integrating solid environmental governance and innovation to address climate change challenges in the healthcare sector effectively. This integrated approach not only helps reduce carbon emissions but also contributes to achieving sustainable outcomes while satisfying a wider range of stakeholders.

Originality/value

This study adds to the existing body of knowledge by highlighting the significant role of environmental governance as a moderator in the relationship between environmental innovation and carbon emission in the healthcare industry. The research findings provide valuable insights for academics, practitioners and decision-makers, emphasizing the need to combine governance and innovation for sustainable outcomes in healthcare sectors.
Conclusion: exploring the intersection of digital nomadism and tourism in a postmodern world
Authors: Günay Semra , Akgiş İlhan Öznur
Published: April 2024

Purpose

The aim of this article is to examine in depth the digital nomad lifestyle and its effects in the context of tourism and to create a perspective for the future by taking into account the findings of the articles in the thematic issue.

Design/methodology/approach

The theme question is examined through a review of the main findings and outcomes of this issue.

Findings

The digital nomad lifestyle stands out as an alternative form of tourism to traditional tourism models. Digital nomads are interested in cultural heritage and are effective in destination marketing just as social media influencers are. Gastronomic preferences and security perceptions of digital nomads play an important role in destination selection. Although digital nomads start out with a desire for independence and freedom, they want to come together with their peers in order to meet their social needs.

Originality/value

This article will serve as a significant resource for understanding the digital nomad lifestyle and for predicting future tourism trends.
Preventing subsequent turnover after downsizing: The role of collective pay for performance practices
Authors: Kim Youngsang , Kim Andrea , Park Tae‐Youn , Oh Eun‐Ji , Eo Seung Soo , Song Kihwan
Published: April 2024

Prior studies have suggested that downsizing events can lead to a contagion of voluntary turnover among employees. In the current study, drawing on the turnover event theory, we propose that the relationship between downsizing and turnover can be nonlinear. We also propose that the presence of collective pay‐for‐performance (PFP) practices is an important but overlooked contingency that moderates the effects of downsizing. By analyzing a dataset collected from 317 firms with 634 firm‐year observations, we found that the relationship between downsizing and voluntary turnover rates takes an attenuated positive form, and that this relationship is mitigated in firms that have more collective PFP practices. Our findings contribute to the literature on downsizing, turnover, and collective PFP practices while also providing a specific practical implication pertaining to the mitigation of the disruptive effects of downsizing.
Making decisions one drink at a time and the “just one drink” effect: A fuzzy‐trace theory model of harmful drinking
Authors: Hayes Bridget B. , Reyna Valerie F. , Edelson Sarah M.
Published: April 2024

Background

Understanding the decision factors that drive harmful alcohol use among young adults is of practical and theoretical importance. We apply fuzzy‐trace theory (FTT) to investigate a potential danger that may arise from the arguably correct notion that a single drink carries no meaningful risk. Decisions that are mentally represented as one drink at a time could contribute to excessive drinking.

Methods

College students (N = 351) made a series of decisions to take or decline eight hypothetical drinks presented one at a time. Outcome measures included each decision, recent alcohol consumption (weekly drinks, peak blood alcohol content, and binges), and alcohol‐related harms (scores on the Brief Young Adult Alcohol Consequences Questionnaire and Alcohol Use Disorders Identification Test). Linear regression models predicted each outcome from sex, perceived risk of a single drink, perceived risk of heavy drinking, perceived consequences of drinking, and general health‐related risk sensitivity.

Results

Consistent with FTT, decisions to have a first drink and up to four additional drinks in short succession were each associated with lower perceived risk of one drink—a “just‐one drink” effect—independent of perceived risks of heavy drinking, perceived consequences of drinking, and general risk sensitivity. Similarly, all measures of recent alcohol consumption and consequent harms were associated with perceived risk of one drink. Participants reporting “zero risk” of a single drink had worse outcomes on all measures than those reporting at least “low risk.”

Conclusions

Results are consistent with the theoretically informed premise that consumption decisions are typically made one drink at a time rather than by deciding the total number of drinks to be consumed in a sitting. When decisions about alcohol use proceed one drink at a time, a perception of zero risk in a single drink may contribute to heavy drinking.
Assessing preconception health in Australia to support better outcomes in the first 2000 days – A critical need for building a core indicator framework
Authors: Subasinghe Asvini K. , Black Kirsten I. , Dorney Edwina , Boyle Jacqueline A.
Published: April 2024

In 2021, the Preconception Health Network Australia co‐developed preconception health core indicators identified as critical to ensuring optimal maternal and child outcomes following conception. We conducted an audit of perinatal databases across each state and territory to identify whether preconception core indicator data were available. Seven health domains co‐developed by the Preconception Health Network were mapped against the data collected in the perinatal databases. Indicator data were lacking across all seven health domains, with data missing for social determinants of health indicators. Better data linkage and developing a national evidence‐based framework would allow ongoing monitoring of women's preconception health nationally.
The burden of Finke Desert race‐related trauma: A 10‐year retrospective descriptive analysis
Authors: Cehic Matthew G. , Knight Casey , Morris David , Essen James Van , Bither Nitin , Williams Kanishka
Published: April 2024

Introduction

The Finke Desert Race is an annual motorsport race (motorbikes, cars and buggies) held in Alice Springs resulting in a significant major trauma burden. This imposes unique challenges in one of the world's most remote healthcare settings.

Objectives

To quantify the volume and characteristics of Finke Desert Race‐related trauma presenting to the Alice Springs Hospital.

Design

A retrospective descriptive study was undertaken to review all patients presenting to the Alice Springs Hospital with Finke Desert Race‐related trauma over a 10‐year period. Information collected included demographic data, injury characteristics, patient disposition and required management.

Findings

Over the 9 years the event was held, 325 patients were admitted to the Alice Springs Hospital. Patients were almost exclusively male (98.8%), with a mean age of 34.75 and residing outside of Alice Springs (82.2%). There were a total of 460 distinct injuries with the clavicle, spine and ribs the three most commonly injured sites. A total of 129 operations were required, of which 19 required retrieval to an interstate centre.

Discussion

Alice Springs is one of the most remote and geographically isolated centres on Earth. This rurality poses unique challenges when trying to coordinate medical and retrieval services, exacerbated for a concentrated, yet highly resource intensive event such as Finke. It has far reaching impacts, placing additional stresses on all aspects of healthcare provision.

Conclusion

This review has quantified the trauma burden of the event for the first time, enabling local and interstate stakeholders' ability to plan an adequate and sustainable response while also enabling the future effectiveness evaluation of recent safety reforms.
Perceived obligation, overconfidence and electric‐bike driving hazards: The double‐edged sword of social network density
Authors: Lu Hongxu , Jiang Li , Wu Ting , Zhang Ke , Lin Li
Published: April 2024

This paper introduces the social network perspective to the context of electric‐bike driving and empirically tests various hypotheses on the relationship between social network density and electric‐bike driving hazards. The results of a three‐wave time‐lagged field study of 1575 electric‐bike drivers showed that social network density had a negative indirect effect on driving hazards, mediated by perceived obligation, and a positive indirect effect on driving hazards, mediated by overconfidence. Furthermore, a strong perceived ethical climate strengthened the negative indirect effect of social network density on driving hazards via perceived obligation and mitigated the positive indirect effect of social network density on driving hazards via overconfidence. This study makes theoretical contributions and provides empirical evidence to support the further exploration of electric‐bike driving safety hazards. It also contributes to the literature on social network density by revealing how it is akin to a double‐edged sword in the context of safety incidents.
Inhibition of RNase 7 by RNase inhibitor promotes inflammation and Staphylococcus aureus growth: Implications for atopic dermatitis
Authors: Rademacher Franziska , Scheel Annika , Gläser Regine , Schröder Lena , Heinemann Nina , Bartels Joachim , Gerdes Sascha , Stölzl Dora , Rodriguez Elke , Döhner Katinka , Weidinger Stephan , Werfel Thomas , Harder Jürgen
Published: April 2024

Background

The antimicrobial ribonuclease RNase 7 is abundantly expressed in the epidermis of lesional skin of atopic dermatitis (AD). Host RNase inhibitor (RI) binds to RNase 7 and blocks its ribonuclease activity. This study aimed to evaluate the impact of RNase 7–RI interactions on AD.

Methods

Cultured human primary keratinocytes, with siRNA‐mediated downregulation of RNase 7 and RI, were stimulated with the synthetic RNA polyinosinic‐polycytidylic acid (poly I:C). Induction of proinflammatory mediators was analyzed by real‐time PCR and ELISA. RI expression in AD non‐lesional and lesional skin biopsies and healthy controls was analyzed by real‐time PCR and immunostaining. RI protein release in vivo on the AD skin surface was determined by western blot. Antimicrobial and ribonuclease assays were used to investigate the functional role of RI.

Results

RNase 7 inhibited the RNA‐induced expression of proinflammatory mediators in keratinocytes. Accordingly, downregulation of RNase 7 in keratinocytes enhanced RNA‐mediated induction of proinflammatory mediators, whereas downregulation of RI had the opposite effect. RI was released by damaged keratinocytes and epidermis. In vivo expression and release of RI on the skin surface were enhanced in lesional AD skin. Rinsing solution from the surface of lesional AD skin blocked the ribonuclease activity of RNase 7. The anti‐Staphylococcus aureus activity of RNase 7 was abrogated by RI.

Conclusions

Our data suggest a novel role of RI as a trigger factor of inflammation in AD by blocking the ribonuclease and antimicrobial activity of RNase 7, thereby enhancing RNA‐mediated inflammation and S. aureus growth.
Acute kidney injury in children hospitalised for febrile urinary tract infection
Authors: Marzuillo Pierluigi , Guarino Stefano , Alfiero Salvatore , Annicchiarico Petruzzelli Luigi , Arenella Mattia , Baccelli Francesco , Brugnara Milena , Corrado Ciro , Delcaro Giulia , Di Sessa Anna , Gallotta Giulia , Lanari Marcello , Lorenzi Maya , Malgieri Gabriele , Miraglia del Giudice Emanuele , Pecoraro Carmine , Pennesi Marco , Picassi Sara , Pierantoni Luca , Puccio Giuseppe , Scozzola Floriana , Taroni Francesca , Tosolini Chiara , Venditto Laura , Pasini Andrea , La Scola Claudio , Montini Giovanni ,   CAKUT‐UTI Study Group of the Italian Society of Pediatric Nephrology
Published: April 2024

Aim

To determine (i) prevalence and the risk factors for acute kidney injury (AKI) in children hospitalised for febrile urinary tract infection (fUTI) and (ii) role of AKI as indicator of an underlying VUR. AKI, in fact, is favoured by a reduced nephron mass, often associated to VUR.

Methods

This retrospective Italian multicentre study enrolled children aged 18 years or younger (median age = 0.5 years) discharged with a primary diagnosis of fUTI. AKI was defined using Kidney Disease/Improving Global Outcomes serum creatinine criteria.

Results

Of 849 children hospitalised for fUTI (44.2% females, median age 0.5 years; IQR = 1.8), 124 (14.6%) developed AKI. AKI prevalence rose to 30% in the presence of underlying congenital anomalies of the kidney and urinary tract (CAKUT). The strongest AKI predictors were presence of CAKUT (OR = 7.5; 95%CI: 3.8–15.2; p = 9.4e‐09) and neutrophils levels (OR = 1.13; 95%CI: 1.08–1.2; p = 6.8e‐07).

At multiple logistic regression analysis, AKI during fUTI episode was a significant indicator of VUR (OR = 3.4; 95%CI: 1.7–6.9; p = 0.001) despite correction for the diagnostic covariates usually used to assess the risk of VUR after the first fUTI episode. Moreover, AKI showed the best positive likelihood ratio, positive predictive value, negative predictive value and specificity for VUR.

Conclusion

AKI occurs in 14.6% of children hospitalised for fUTI and is a significant indicator of VUR.
Old by obsolescence: The paradox of aging in the digital era
Authors: Llorca Albareda Joan , García‐Barranquero Pablo
Published: April 2024

Geroscience and philosophy of aging have tended to focus their analyses on the biological and chronological dimensions of aging. Namely, one ages with the passage of time and by experiencing the cellular‐molecular deterioration that accompanies this process. However, our concept of aging depends decisively on the social valuations held about it. In this article, we will argue that, if we study social aging in the contemporary world, a novel phenomenon can be identified: the paradox of aging in the digital era. If the social understanding of aging today is linked to unproductivity and obsolescence; then there is a possibility that, given the pace of change of digital technologies, we become obsolete at an early chronological and biological age, and therefore, feel old at a younger age. First, we will present the social dimension of aging based on Rowe and Kahn's model of successful aging. We will also show that their notion of social aging hardly considers structural aspects and weakens their approach. Second, departing from social aging in its structural sense, we will develop the paradox of aging in the digital era. On the one hand, we will explain how the institutionalization of aging has occurred in modern societies and how it is anchored in the concepts of obsolescence and productivity. On the other hand, we will state the kind of obsolescence that digitalization produces and argue that it can make cohorts of biologically and chronologically young individuals obsolete, and thus they would be personally and socially perceived as old.
Hydroxymethylglutaryl‐CoA reductase activity is essential for mitochondrial β‐oxidation of fatty acids to prevent lethal accumulation of long‐chain acylcarnitines in the mouse liver
Authors: Liepinsh Edgars , Zvejniece Liga , Clemensson Laura , Ozola Melita , Vavers Edijs , Cirule Helena , Korzh Stanislava , Skuja Sandra , Groma Valerija , Briviba Monta , Grinberga Solveiga , Liu Wen , Olszewski Paweł , Gentreau Mélissa , Fredriksson Robert , Dambrova Maija , Schiöth Helgi B.
Published: April 2024

Background and Purpose

Statins are competitive inhibitors of 3‐hydroxy‐3‐methylglutaryl coenzyme A (HMG‐CoA) reductase (HMGCR), and exert adverse effects on mitochondrial function, although the mechanisms underlying these effects remain unclear. We used a tamoxifen‐induced Hmgcr‐knockout (KO) mouse model, a multi‐omics approach and mitochondrial function assessments to investigate whether decreased HMGCR activity impacts key liver energy metabolism pathways.

Experimental Approach

We established a new mouse strain using the Cre/loxP system, which enabled whole‐body deletion of Hmgcr expression. These mice were crossed with Rosa26Cre mice and treated with tamoxifen to delete Hmgcr in all cells. We performed transcriptomic and metabolomic analyses and thus evaluated time‐dependent changes in metabolic functions to identify the pathways leading to cell death in Hmgcr‐KO mice.

Key Results

Lack of Hmgcr expression resulted in lethality, due to acute liver damage caused by rapid disruption of mitochondrial fatty acid β‐oxidation and very high accumulation of long‐chain (LC) acylcarnitines in both male and female mice. Gene expression and KO‐related phenotype changes were not observed in other tissues. The progression to liver failure was driven by diminished peroxisome formation, which resulted in impaired mitochondrial and peroxisomal fatty acid metabolism, enhanced glucose utilization and whole‐body hypoglycaemia.

Conclusion and Implications

Our findings suggest that HMGCR is crucial for maintaining energy metabolism balance, and its activity is necessary for functional mitochondrial β‐oxidation. Moreover, statin‐induced adverse reactions might be rescued by the prevention of LC acylcarnitine accumulation.
A case of excisionally remitted indolent NK‐cell enteropathy in the oral cavity and a mini‐review
Authors: Li Xiangyun , Li Zhu , Zhou Xiaoge , Zheng Yuanyuan , Zhang Yanlin , Xie Jianlan
Published: April 2024

Benign natural killer cell enteropathy (NKCE) was first identified in the gastrointestinal (GI) tract. Notably, instances of NKCE have previously been observed at various sites other than the GI tract, including the gallbladder, lymph nodes, esophagus, and female genital tract. Typical NKCE manifests as an NK‐cell immunohistological phenotype, with or without TCR rearrangement, and is characterized by the absence of Epstein–Barr virus (EBV) infection and protracted clinical progression. The misdiagnosis of NKT‐cell lymphoma has resulted in some patients receiving chemotherapy, while in other instances, the patients' conditions resolved without treatment and showed no evidence of disease recurrence or progression during follow‐up examinations. In this paper, we describe a unique case of EBV‐negative NKCE occurring in the oral cavity, the first time such a case has been documented. The tumor completely resolved after an excisional biopsy, and subsequent follow‐up did not reveal any signs of disease recurrence.
Paediatric antibody prevalence in seizure score to predict autoimmune aetiology in seizure disorders
Authors: Mori Takayuki , Matsuda Shimpei , Nishida Hiroya , Kohyama Kuniko , Fukuda Mitsumasa , Sakuma Hiroshi
Published: April 2024

Aim

To modify the antibody prevalence in epilepsy (APE) score of children with suspected autoimmune central nervous system disease with seizures.

Methods

We retrospectively analysed the cerebrospinal fluid of 157 children (aged 0–18 years) with suspected autoimmune central nervous system disease for antineuronal antibodies in our laboratory from 2016 to 2023. Participants were randomly divided into the development cohort (n = 79, 35 females; median 7 years, SD 4 years 7 months, range 4–11 years) and validation cohort (n = 78, 28 females; median 7 years, SD 4 years 5 months, range 4–12 years). A paediatric antibody prevalence in seizure (PAPS) score was created for one cohort and evaluated in the other. Seven variables were selected through univariate and multivariate analysis to create a PAPS score.

Results

One hundred and fifty‐seven children who fulfilled the inclusion criteria were enrolled; 49 tested positive for antineuronal antibodies. The sensitivity and specificity of an APE score of 4 and greater were 92% and 22.2% respectively; the sensitivity and specificity of a PAPS score of 2.5 and greater were 83.3% and 77.8% respectively. The area under the curve was 0.832 (95% confidence interval = 0.743–0.921), which was significantly better than that for the APE score (p < 0.001).

Interpretation

The APE score had high sensitivity but low specificity in children. The PAPS score may be useful for determining the need for antineuronal antibody testing.

What this paper adds

The antibody prevalence in epilepsy (APE) score had high sensitivity but low specificity in children.

The sensitivity and specificity of the paediatric antibody prevalence in seizure (PAPS) score were 83.3% and 77.8% respectively.

There were significant differences in the area under the curve for the APE and PAPS scores.