bluuebunny/crossref_metadata_2025 huggingface dataset:
A functional single nucleotide polymorphism upstream of the collagen type III gene may contribute to catastrophic fracture risk in Thoroughbred horses
Authors: Lago Esther Palomino , Baird Arabella , Blott Sarah C. , McPhail Rhona E. , Ross Amy C. , Durward-Akhurst Sian A. , Guest Deborah J.
Published: June 2023

Fractures caused by bone overloading are a leading cause of euthanasia in Thoroughbred racehorses. The risk of fatal fracture has been shown to be influenced by both environmental and genetic factors but, to date, no specific genetic mechanisms underpinning fracture have been identified. The aim of this study was to utilise a genome-wide polygenic risk score to establish anin vitrocell system to study bone gene regulation in horses at high and low genetic risk of fracture. Candidate gene expression analysis revealed differential expression ofCOL3A1andSTAT1genes in osteoblasts derived from high and low risk horses. Whole genome sequencing of fracture case and control horses revealed a single nucleotide polymorphism (SNP) upstream ofCOL3A1that was confirmed in a larger cohort to be significantly associated with fracture. Bioinformatics tools predicted that this SNP may impact the binding of the transcription factor SOX11. Gene modulation demonstrated SOX11 is upstream ofCOL3A1and the region binds to nuclear proteins. Furthermore, luciferase assays demonstrated that the region containing the SNP has promoter activity. However, the specific effect of the SNP depends on the broader genetic background of the cells and suggest other factors may also be involved in regulatingCOL3A1expression. In conclusion, this approach provides a powerful means to identify novel DNA variants and understand their mechanism of action to enable the development of new ways to identify and treat horses at high risk of a catastrophic fracture.
Serine ubiquitination of p62 regulates Nrf2 dependent redox homeostasis
Authors: Mukherjee Rukmini , Hoffmann Marina , Gonzalez Alexis , Bhattacharya Anshu , Kuncha Santosh Kumar , Rathore Rajeshwari , Shin Donghyuk , Colby Thomas , Matic Ivan , Misra Mohit , Dikic Ivan
Published: June 2023

The KEAP1–Nrf2 axis is essential for the cellular response against metabolic and oxidative stress. KEAP1 is an adaptor protein of Cullin-3 ubiquitin ligase that controls the cellular levels of Nrf2, a critical transcription factor of several cytoprotective genes. Oxidative stress, defective autophagy and pathogenic infections activate Nrf2 signaling through phosphorylation of the adaptor protein p62, which competes with Nrf2 for binding to KEAP1. Here we show that phosphoribosyl-linked serine ubiquitination of p62 catalyzed by SidE effectors ofLegionella pneumophilacontrols Nrf2 signaling and cell metabolism uponLegionellainfection. Serine ubiquitination of p62 sterically blocks its binding to KEAP1, resulting in Nrf2 ubiquitination and degradation. This reduces Nrf2-dependent antioxidant synthesis in the early phase of infection. Levels of serine ubiquitinated p62 diminish in the later stage of infection allowing the expression of Nrf2-target genes; resulting in a differential regulation of the host metabolome and proteome in a Nrf2 dependent manner.
Synergistic genomic mechanisms of adaptation to ocean acidification in a coral holobiont
Authors: Leiva Carlos , Pérez-Portela Rocío , Lemer Sarah
Published: June 2023

Ocean acidification, caused by anthropogenic CO2emissions, is predicted to have major consequences for reef-building corals, jeopardizing the scaffolding of the most biodiverse marine habitats. However, whether corals can adapt to ocean acidification and how remains unclear. We addressed these questions by re-examining transcriptome and genome data ofAcropora milleporacoral holobionts from volcanic CO2seeps with end-of-century pH levels. We show that adaptation to ocean acidification is a wholistic process involving the three main compartments of the coral holobiont. We identified 441 coral host candidate adaptive genes involved in calcification, response to acidification, and symbiosis; population genetic differentiation in dinoflagellate photosymbionts; and consistent transcriptional microbiome activity despite microbial community shifts. Coral holobionts from natural analogues to future ocean conditions harbor beneficial genetic variants with far-reaching rapid adaptation potential. In the face of climate change, these populations require immediate conservation strategies as they could become key to coral reef survival.
Non-cognate immunity proteins provide broader defenses against interbacterial effectors in microbial communities
Authors: Knecht Abigail , Sirias Denise , Utter Daniel R. , Gibbs Karine A.
Published: June 2023

Dense microbial communities, like the gut and soil microbiomes, are dynamic societies. Bacteria can navigate these environments by deploying proteins that alter foreign cells’ behavior, such as interbacterial effectors. Current models suggest that adjacent sibling cells are protected by an immunity protein, as compared to toxin-antitoxin systems that act only within the effector-producing cell. A prevailing hypothesis is that immunity proteins binding to specific (cognate) protein partners is sufficient to disrupt effector function. Further, there is little-to-no crosstalk with other non-cognate effectors. In this research, we build on sporadic reports challenging these hypotheses. We show that immunity proteins from a newly defined protein family can bind and protect against non-cognate PD-(D/E)XK-containing effectors from diverse phyla. We describe the domains essential for binding and function and show that binding alone is insufficient for protective activity. Moreover, we found that these effector and immunity genes co-occur in individual human microbiomes. These results expand the growing repertoire of bacterial protection mechanisms and the models on how non-cognate interactions impact community structure within complex ecosystems.
Literate programming for iterative design-build-test-learn cycles in bioengineering
Authors: Petersen Søren , Levassor Lucas , Pedersen Christine M. , Madsen Jan , Hansen Lea G. , Zhang Jie , Haidar Ahmad K. , Frandsen Rasmus , Keasling Jay D. , Weber Tilmann , Sonnenschein Nikolaus , Jensen Michael K.
Published: June 2023

Synthetic biology dictates the data-driven engineering of biocatalysis, cellular functions, and organism behavior. Integral to synthetic biology is the aspiration to efficiently find, access, interoperate, and reuse high-quality data on genotype-phenotype relationships of native and engineered biosystems under FAIR principles, and from this facilitate forward-engineering strategies. However, biology is complex at the regulatory level, and noisy at the operational level, thus necessitating systematic and diligent data handling at all levels of the design, build, and test phases in order to maximize learning in the iterative design-build-test-learn engineering cycle. To enable user-friendly simulation, organization, and guidance for the engineering of complex biosystems, we have developed an open-source python-based computer-aided design and analysis platform operating under a literate programming user-interface hosted on Github. The platform is called teemi and is fully compliant with FAIR principles. In this study we apply teemi for i) designing and simulating bioengineering, ii) integrating and analyzing multivariate datasets, and iii) machine-learning for predictive engineering of a metabolic pathway designs for production of a key precursor to medicinal alkaloids. The teemi platform is publicly available atPyPiandGitHub.
The effect of social support on teleworker environment and work engagement: a multimethod analysis
Authors: Kakkar Shiva , Kuril Samvet , Saha Surajit , Gupta Parul , Singh Swati
Published: June 2023

Purpose

Employing the “Job demands-resources (JD-R)” framework, this study examines the impact of co-occurring social supports (supervisor, coworker, and family support) on the telework environment and employee engagement.

Design/methodology/approach

The study uses a multimethod approach. Data from 294 employees belonging to Indian technology organizations were collected and analyzed using the partial least squares (PLS)-based structure equation modeling software SmartPLS4. Following this, necessary condition analysis (NCA) was carried out using the NCA package for R.

Findings

Telework environment was found to mediate the relationship between social support and work engagement. Supervisor support and instrumental family support were identified as predictors as well as necessary conditions for telework environment. Coworker support was identified both as a predictor and necessary condition for telework environment. Although emotional family support was found to be a predictor of telework environment, it was not identified as a necessary condition.

Practical implications

The findings indicate that coworker support and family instrumental support are as important for telework success as supervisor support. Moreover, our findings suggest that varying levels of telework environments (low, moderate, and high) may necessitate distinct social support configurations. Consequently, organizations should match their social support configuration to match their overall teleworking strategy.

Originality/value

A basic premise of the JD-R framework is that resources exist in caravans (bundles). However, previous research (in telework) has concentrated on only one or two kinds of social support, that too in varying situational contexts, limiting generalizability of the findings. This has also produced inconsistent conclusions concerning the role of support providers such as coworkers and family. Recent developments in JD-R also suggest that the role of resources may vary in terms of their importance (necessity) for work engagement. By augmenting standard regression-based techniques with NCA, the authors explore these issues to provide a more thorough understanding of the influence of social supports on work engagement in telework situations.
To disclose or not disclose, is no longer the question – effect of AI-disclosed brand voice on brand authenticity and attitude
Authors: Kirkby Alexandra , Baumgarth Carsten , Henseler Jörg
Published: June 2023

Purpose

This paper aims to explore consumer perception of “brand voice” authenticity, brand authenticity and brand attitude when the source of text is disclosed as either artificial intelligence (AI)-generated or human-written.

Design/methodology/approach

A 3 × 3 experimental design using Adidas marketing texts disclosed as either “AI” or “human”, or not disclosed was applied to data gathered online from 624 English-speaking students.

Findings

Text disclosed as AI-generated is not perceived as less authentic than that disclosed as human-written. No negative effect on brand voice authenticity and brand attitude results if an AI-source is disclosed.

Practical implications

Findings offer brand managers the potential for cost and time savings but emphasise the strong effect of AI technology on perceived brand authenticity and brand attitude.

Originality/value

Results show that brands can afford to be transparent in disclosing the use of AI to support brand voice as communicated in product description or specification or in chatbot text.
Who let the dogs out? How underdog biographies told by family firms affect consumers’ brand attitude
Authors: Lude Maximilian , Prügl Reinhard , Rauschendorfer Natalie
Published: June 2023

Purpose

Brand stories are often created around the company’s humble beginnings as an underdog. The authors explore the effects of who is telling the underdog story and thus draw attention to the nature of the brand source by differentiating between family and non-family firms. The authors expect that who is telling the underdog story impacts consumers’ attitude toward the brand in terms of brand authenticity and trustworthiness perceptions.

Design/methodology/approach

The authors conducted an online experiment with a 2 × 2 between-subject design and an overall sample size of 314 respondents.

Findings

Most importantly, the authors find that the family-firm nature of the brand storyteller significantly impacts the underdog effect. The positive effects of underdog biographies on brand attitude in terms of authenticity and trustworthiness loom significantly larger for family firms compared with non-family firms.

Practical implications

The authors find that the underdog effect is significantly stronger for family firms that tell the underdog story. Managers of family firms with underdog roots should take advantage of this finding by integrating underdog stories into their marketing concepts. The findings of this study show that the communication of a company’s roots can serve as a valuable tool to build and maintain a positive brand image and help to increase purchase intentions, which is particularly true for firms capitalizing on their family nature when telling the underdog story.

Originality/value

The authors combine research on brand stories using the underdog effect with research on the consumer’s perception of family firms, further exploring the role of the brand storyteller in underdog narratives, resulting in important theoretical as well as practical implications.
Investor’s values and investment decision towards ESG stocks
Authors: Raut Rajdeep Kumar , Shastri Niranjan , Mishra Akshay Kumar , Tiwari Aviral Kumar
Published: June 2023

Purpose

This study aims to investigate factors that influence the attitudes and intentions of investors towards environmental, social and governance (ESG) stocks in the presence of perceived risk as a moderator.

Design/methodology/approach

Data was collected through an online survey method from 341 investors with more than three years of investing experience. Smart PLS was used to analyse the data using two-stage structural equation modelling. First, a measurement model was performed for construct reliability and validity, followed by path analysis (structural model) for hypothesis testing and overall model predictability.

Findings

The findings show that both environmental concern (altruistic value) and economic concern (egoistic value) are crucial for the attitude and intention of investors to invest in ESG-backed stocks; however, environmental concern was found to be a more significant predictor of their behaviour, showing evidence of pro-environmental values in the decision-making of utility-seeking individuals. No significant impact of perceived risk was evident as a moderator of the relationship between attitude and intention towards ESG stocks.

Practical implications

The study's findings have implications for fund managers, policymakers, and the government. Values as antecedents were found to be influential in shaping investors’ attitudes and intentions towards the environmental cause. Fund managers could include more ESG-compliant companies in their portfolios, and the government can play an important role in encouraging investors by providing financial incentives. Corporates should also take strategic steps to adopt green production processes to secure long-term, sustainable capital funding.

Originality/value

To the best of the authors’ knowledge, there has been no research done in the field of ESG investing that takes into account the values (both altruistic and egoistic) of investors as potential antecedents of their attitudes and intentions.
Predicting geometric errors and failures in additive manufacturing
Authors: Ntousia Margarita , Fudos Ioannis , Moschopoulos Spyridon , Stamati Vasiliki
Published: June 2023

Purpose

Objects fabricated using additive manufacturing (AM) technologies often suffer from dimensional accuracy issues and other part-specific problems. This study aims to present a framework for estimating the printability of a computer-aided design (CAD) model that expresses the probability that the model is fabricated correctly via an AM technology for a specific application.

Design/methodology/approach

This study predicts the dimensional deviations of the manufactured object per vertex and per part using a machine learning approach. The input to the error prediction artificial neural network (ANN) is per vertex information extracted from the mesh of the model to be manufactured. The output of the ANN is the estimated average per vertex error for the fabricated object. This error is then used along with other global and per part information in a framework for estimating the printability of the model, that is, the probability of being fabricated correctly on a certain AM technology, for a specific application domain.

Findings

A thorough experimental evaluation was conducted on binder jetting technology for both the error prediction approach and the printability estimation framework.

Originality/value

This study presents a method for predicting dimensional errors with high accuracy and a completely novel approach for estimating the probability of a CAD model to be fabricated without significant failures or errors that make it inappropriate for a specific application.
A conceptual framework of total quality management on innovation performance in the banking sector
Authors: Ahinful Abraham Ato , Opoku Mensah Abigail , Koomson Samuel , Nyarko Felix Kwame , Nkrumah Edmund
Published: June 2023

Purpose

The “United Nations' Sustainable Development Goal” 9 seeks to “… foster innovation” in all sectors of an economy. Thus, this conceptual piece addresses the indirect effect of innovative behaviour (INB) between total quality management (TQM) and innovation performance (INP). It further explores the context-contingent effect of four external factors [government regulation (GOV), market dynamism (MKD), competitive intensity (CMP) and technological turbulence (TUR)] on the TQM–INB linkage.

Design/methodology/approach

By incorporating both theoretical and empirical works in the fields of strategic management, innovation and business performance, this conceptual piece constructs a conceptual model, using a systematic literature review, alongside suppositions that can be tested in further studies.

Findings

This conceptual piece puts forward that TQM will be favourably connected to INP, and this favourable association will be mediated by INB. Moreover, GOV, MKD, CMP and TUR will have a favourable context-contingent effect on the favourable direct connection between TQM and INB.

Research limitations/implications

This conceptual piece affords suggestions for both practitioners and researchers alike in the areas of innovative and strategic decision-making in banking establishments for reinforcing INP by introducing TQM, INB, GOV, MKD, CMP and TUR as innovative-strategic tools. It also delivers suggestions for forthcoming academics to examine this conceptual piece, empirically, in diverse banking sites worldwide.

Practical implications

Practical lessons for managers, employees, customers and consultants within the banking sector for the superior advantage of all key stakeholders are deliberated.

Originality/value

This study provides a new model to demonstrate how TQM leads to INP by passing through INB of employees, and how TQM fosters INB under diverse degrees of GOV, MKD, CMP and TUR. It shows how internal factors (7 TQM dimensions) and external factors (GOV, MKD, CMP and TUR) interact to foster employee INB. It also underscores the theoretical authority of three theories utilised, both individually and in combination, by using them to explain new relationships.
Trash or treasure: Rhizome conservation during drought
Authors: Lubbe Frederick Curtis , Bitomský Martin , Bartoš Michael , Marešová Iveta , Martínková Jana , Klimešová Jitka
Published: June 2023

The role of storage carbohydrates in plant carbon economy is currently disputed as possibly passive accumulation when other resources are limiting growth, or part of a conservative growth strategy as insurance for regrowth and stress response. One indication may be the fate of carbohydrates in senescing rhizomes, as either translocated to be retained in the live and growing end of the rhizome or kept within the senescing rhizome end and lost into the soil for it to decompose.

To examine carbohydrate storage in senescing rhizomes, eight rhizomatous species were grown in a split‐pot design with one compartment containing the forward‐growing and younger end of the rhizome and another containing the older end. Both compartments were either watered (control) or the older one was left un‐watered (drought treatment) to trigger rhizome senescence and potential carbohydrate translocation. Plant growth, root traits, and non‐structural carbohydrate types and concentrations were assessed in four sequential harvests.

Drought treatment plants had higher rhizome dry matter content. Younger rhizome parts produced higher new rhizome and above‐ground biomass than older rhizome parts. Carbohydrate concentrations in rhizomes remained consistent for both treatments, younger and older rhizome parts, and all harvests, probably because of the translocation of water from the watered to the dry compartment to prevent senescence and rhizome loss.

Contrary to expectations, the experimental treatment did not trigger rhizome senescence: plants responded by conserving the rhizome and resources within, rather than by losing their older parts. The invariant composition and concentration of carbohydrates within the rhizome suggest that rhizomes are essential plant organs and the storage carbohydrates they contain are necessary for regrowth after stress.

Read the free Plain Language Summary for this article on the Journal blog.
The evolution and functional divergence of 10 Apolipoprotein D‐like genes in Nilaparvata lugens
Authors: Lu Jia‐Bao , Ren Peng‐Peng , Li Qiao , He Fang , Xu Zhong‐Tian , Wang Sai‐Nan , Chen Jian‐Ping , Li Jun‐Min , Zhang Chuan‐Xi
Published: June 2023

Apolipoprotein D (ApoD), a member of the lipocalin superfamily of proteins, is involved in lipid transport and stress resistance. Whereas only a single copy of the ApoD gene is found in humans and some other vertebrates, there are typically several ApoD‐like genes in insects. To date, there have been relatively few studies that have examined the evolution and functional differentiation of ApoD‐like genes in insects, particularly hemi‐metabolous insects. In this study, we identified 10 ApoD‐like genes (NlApoD1−10) with distinct spatiotemporal expression patterns in Nilaparvata lugens (BPH), which is an important pest of rice. NlApoD1−10 were found to be distributed on 3 chromosomes in a tandem array of NlApoD1/2, NlApoD3−5, and NlApoD7/8, and show sequence and gene structural divergence in the coding regions, indicating that multiple gene duplication events occurred during evolution. Phylogenetic analysis revealed that NlApoD1−10 can be clustered into 5 clades, with NlApoD3−5 and NlApoD7/8 potentially evolving exclusively in the Delphacidae family. Functional screening using an RNA interference approach revealed that only NlApoD2 was essential for BPH development and survival, whereas NlApoD4/5 are highly expressed in testes, and might play roles in reproduction. Moreover, stress response analysis revealed that NlApoD3−5/9, NlApoD3−5, and NlApoD9 were up‐regulated after treatment with lipopolysaccharide, H2O2, and ultraviolet‐C, respectively, indicating their potential roles in stress resistance.
The role of collective impact in improving nutrition. A scoping review
Authors: Pyke Kate , Palermo Claire , Kleve Sue
Published: June 2023

Background

Collective impact is gaining traction to improve population health outcomes. This study aimed to determine where and how collective impact is being used in nutrition and describe current understandings of its impacts or results on health or nutrition outcomes.

Methods

A systematic scoping review was undertaken with four databases (‘CINAHL Plus’, ‘Sociological Abstracts’, ‘PsychInfo’, and ‘OVID Medline’) using the search term ‘Collective Impact’ from 2011 up to November 2022. All studies were screened independently by two authors. Data were extracted and synthesised narratively.

Results

A total of 712 different documents were identified, with four studies included in the synthesis. Collective impact approaches focussed on breastfeeding, reducing sugar‐sweetened beverage consumption, increasing access to healthy food, and obesity. Across the four included studies, promising results in improving health and nutrition were reported.

Conclusion

Evaluating and reporting on the outcomes of collective impact initiatives in nutrition using robust methods is needed.
Assembly of female and male hihi genomes (stitchbird; Notiomystis cincta) enables characterization of the W chromosome and resources for conservation genomics
Authors: Bailey Sarah , Guhlin Joseph , Senanayake Dinindu S. , Scherer Phoebe , Brekke Patricia , Ewen John G. , Santure Anna W. , Whibley Annabel
Published: June 2023

A high‐quality reference genome can be a valuable resource for threatened species by providing a foundation to assess their evolutionary potential to adapt to future pressures such as environmental change. We assembled the genome of a female hihi (Notiomysits cincta), a threatened passerine bird endemic to Aotearoa New Zealand. The assembled genome is 1.06 Gb, and is of high quality and highly contiguous, with a contig N50 of 7.0 Mb, estimated QV of 44 and a BUSCO completeness of 96.8%. A male assembly of comparable quality was generated in parallel. A population linkage map was used to scaffold the autosomal contigs into chromosomes. Female and male sequence coverage and comparative genomics analyses were used to identify Z‐, and W‐linked contigs. In total, 94.6% of the assembly length was assigned to putative nuclear chromosome scaffolds. Native DNA methylation was highly correlated between sexes, with the W chromosome contigs more highly methylated than autosomal chromosomes and Z contigs. 43 differentially methylated regions were identified, and these may represent interesting candidates for the establishment or maintenance of sex differences. By generating a high‐quality reference assembly of the heterogametic sex, we have created a resource that enables characterization of genome‐wide diversity and facilitates the investigation of female‐specific evolutionary processes. The reference genomes will form the basis for fine‐scale assessment of the impacts of low genetic diversity and inbreeding on the adaptive potential of the species and will therefore enable tailored and informed conservation management of this threatened taonga (treasured) species.
Hyaluronan synthesis inhibition normalizes ethanol‐enhanced hepatic stellate cell activation
Authors: Kotulkar Manasi , Robarts Dakota R. , Lin‐Rahardja Kristi , McQuillan Tara , Surgnier Jordan , Tague Sarah E. , Czerwinski Maciej , Dennis Katie L. , Pritchard Michele T.
Published: June 2023

Background

Chronic ethanol overconsumption promotes alcohol‐associated liver disease (ALD), characterized by hepatocyte injury, inflammation, hepatic stellate cell (HSC) activation, and fibrosis. Hyaluronan (HA) concentration is greater in livers and blood from advanced ALD patients than patients with advanced non‐ALD. In the liver, HSCs are the major HA producers. The relationship between ethanol, HA, and HSC activation is incompletely understood. Thus, here, we tested the hypothesis that ethanol enhances HSC activation in a HA‐dependent manner.

Methods

Liver tissue microarrays (TMAs) containing steatotic livers from donors with or without a history of alcohol consumption were used to measure HA and collagen content. Mice were fed a moderate (2%, v/v) ethanol‐containing diet or pair‐fed control diet for 2 days, after which they were given a single carbon tetrachloride (CCl4) injection. To inhibit HA synthesis, we provided 4‐methylumbelliferone (4MU) daily. We used LX2 cells, a human HSC cell line, to determine the impact ethanol had on LPS responses, with or without concurrent 4MU exposure.

Results

CCl4 induced liver injury, but it did not differ between ethanol or control diet fed mice with or without 4MU treatment. Ethanol feeding enhanced CCl4‐induced hepatic HA content, which was paralleled by HA synthase (Has)2 transcript abundance; 4MU treatment normalized both. Consistently, HSC activation, assessed by measuring αSMA mRNA and protein, was induced by CCl4 exposure, enhanced by ethanol feeding, and normalized by 4MU. Hepatic transcripts, but not protein, for Ccl2 were enhanced by ethanol feeding and normalized by 4MU exposure. Finally, ethanol‐exposed LX2 cells made more LPS‐stimulated CCL2 mRNA and protein than cells not exposed to ethanol; 4MU prevented this.

Conclusion

These data show that ethanol augments HSC activation through HA synthesis and enhances hepatic profibrogenic features. Therefore, targeting HSC HA production could potentially attenuate liver disease in ALD patients.
Mechanosensory cells in annelid oligochaete Lumbricus terrestris (Linnaeus, 1758): A new insight on worm evolution
Authors: Alesci Alessio , Messina Emmanuele , Zuwala Krystyna , Fumia Angelo , Miller Anthea , D'Angelo Roberta , Kuciel Michal , Albano Marco , Savoca Serena , Capillo Gioele
Published: June 2023

Ciliated and non‐ciliated mechanosensory cells in invertebrates have intricate cytoskeletal structures that, combined with microtubules, act as a mechanical link between external stimulus and signal processing. As a result, they can perceive forces like touch, cuticle deformation, gravity and sound. Through the expression of antibodies against serotonin (5‐HT), calbindin, inducible nitric oxide synthase (iNOS) and α‐smooth muscle actin (αSMA), this research aims to investigate mechanosensory cells in the integument of Lumbricus terrestris (Linnaeus, 1758) in an evolutionary perspective. In the epidermis, we discovered isolated mechanosensory cells that were immunopositive to every antibody examined. Our findings improve the knowledge and the evolution of annelid sensory biology adding new insights on the sensory signal transduction and help to better understand the morpho‐structural adaptations of invertebrate skin on an evolutionary scale and to give more taxonomic data for species distinction.
From logic to action on flourishing for all
Authors: Shrivastava Paul , Grant John H.
Published: June 2023

There is general agreement among sustainability professionals that sustainability needs to be implemented for all and not selectively for just a few. We argue that it is time to urgently act on sustainability and climate change. We suggest plausible actions by businesses, governments, consumers investors, and others. Not acting now risks the closing of a window of opportunity and potential social and economic instabilities.
Small but powerful—local value chains and sustainability‐oriented approaches in the agri‐food sector
Authors: Royer Susanne , Simon Maike
Published: June 2023

Regional and local value creation is seen as one solution for reducing the environmental impact of the agri‐food system. The point of reference for this research is the powerless position of small actors in agri‐food chains. This paper gives insights into the motivation of small‐scale producers in developed countries to exit national and export markets and to opt for a sustainability orientation. Specifically, we explore how the powerlessness of small actors in global value chains may fuel the formation of regional and local value chains. Through a regional case study, we map the dairy value system and identify three different value chain structures in the Northern German dairy industry. Then, we illustrate how some small (organic) raw milk producers have changed their position in the value chain and bargaining strength by following different upgrading strategies. Their increase in bargaining power comes with efficiency losses and increased risk. Implications for small‐scale producers and society are discussed and brought together in a framework that demonstrates the drivers and challenges for sustainability‐oriented small‐scale agricultural producers to achieve a stable and competitive position within the market.
Characterization and clinical implications of different malignant transformation patterns in diffuse low‐grade gliomas
Authors: Jiang Haihui , Zhu Qinghui , Wang Xijie , Li Mingxiao , Shen Shaoping , Yang Chuanwei , Zhao Xuzhe , Li Ming , Ma Guofo , Zhao Xiaofang , Chen Xiaodong , Yang Jun , Lin Song
Published: June 2023

Malignant transformation (MT) of low‐grade gliomas (LGGs) to a higher‐grade variant seems inevitable, yet it remains unclear which LGG patients will progress to grade 3 or even directly to grade 4 after receiving a long course of treatment. To elucidate this, we conducted a retrospective cohort study based on 229 adults with recurrent LGG. Our study aimed to disclose the characteristics of different MT patterns and to build predictive models for patients with LGG. Patients were allocated into group 2–2 (n = 81, 35.4%), group 2–3 (n = 91, 39.7%), and group 2–4 (n = 57, 24.9%), based on their MT patterns. Patients who underwent MT showed lower Karnofsky performance scale (KPS) scores, larger tumor sizes, smaller extents of resection (EOR), higher Ki‐67 indices, lower rates of 1p/19q codeletion, but higher rates of subventricular involvement, radiotherapy, chemotherapy, astrocytoma, and post‐progression enhancement (PPE) compared with those in group 2–2 (p < 0.01). On multivariate logistic regression, 1p/19q codeletion, Ki‐67 index, radiotherapy, EOR, and KPS score were independently associated with MT (p < 0.05). Survival analyses demonstrated that patients in group 2–2 had the longest survival, followed by group 2–3 and then group 2–4 (p < 0.0001). Based on these independent parameters, we constructed a nomogram model that exhibited superior potential (sensitivity: 0.864, specificity: 0.814, and accuracy: 0.843) compared with PPE in early prediction of MT. Combining the factors of 1p/19q codeletion, Ki‐67 index, radiotherapy, EOR, and KPS score that were presented at initial diagnosis could precisely forecast the subsequent MT patterns of patients with LGG.
Development and validation of a nomogram to provide individualized predictions of functional outcomes in patients with convulsive status epilepticus at 3 months: The modified END‐IT tool
Authors: Wang Xuan , Wang Yuan‐Yuan , Gao Qiong , Zhang Yao‐Yao , Wan Jian , Song Chang‐Geng , Wei Jing‐Ya , Kang Xiao‐Gang , Yang Fang , Jiang Wen
Published: June 2023

Aims

The prediction of outcomes in convulsive status epilepticus (CSE) remains a constant challenge. The Encephalitis‐Nonconvulsive Status Epilepticus‐Diazepam Resistance‐Image Abnormalities‐Tracheal Intubation (END‐IT) score was a useful tool for predicting the functional outcomes of CSE patients, excluding cerebral hypoxia patients. With further understanding of CSE, and in view of the deficiencies of END‐IT itself, we consider it necessary to modify the prediction tool.

Methods

The prediction model was designed from a cohort of CSE patients from Xijing Hospital (China), between 2008 and 2020. The enrolled subjects were randomly divided into training cohort and validation cohort as a ratio of 2:1. The logistic regression analysis was performed to identify the predictors and construct the nomogram. The performance of the nomogram was assessed by calculating the concordance index, and creating calibration plots to check the consistency between the predicted probabilities of poor prognosis and the actual outcomes of CSE.

Results

The training cohort included 131 patients and validation cohort included 66 patients. Variables included in the nomogram were age, etiology of CSE, non‐convulsive SE, mechanical ventilation, abnormal albumin level at CSE onset. The concordance index of the nomogram in the training and validation cohorts was 0.853 (95% CI, 0.787–0.920) and 0.806 (95% CI, 0.683–0.923), respectively. The calibration plots showed an adequate consistency between the reported and predicted unfavorable outcomes of patients with CSE at 3 months after discharge.

Conclusions

A nomogram for predicting the individualized risks of poor functional outcomes in CSE was constructed and validated, which has been an important modification of END‐IT score.
Integrated transcriptomics reveals the brain and blood biomarkers in Alzheimer's disease
Authors: Yu Haitao , Wang Fangzhou , Wu Jia‐jun , Gong Juan , Bi Shuguang , Mao Yumin , Jia Dongdong , Chai Gao‐shang
Published: June 2023

Background

The systematic molecular associations between the peripheral blood cells and brain in Alzheimer's disease (AD) remains unclear, which hinders our understanding of AD pathological mechanisms and the exploration of new diagnostic biomarkers.

Methods

Here, we performed an integrated analysis of the brain and peripheral blood cells transcriptomics to establish peripheral biomarkers of AD. By employing multiple statistical analyses plus machine learning, we identified and validated multiple regulated central and peripheral network in patients with AD.

Results

By bioinformatics analysis, a total of 243 genes were differentially expressed in the central and peripheral systems, mainly enriched in three modules: immune response, glucose metabolism and lysosome. In addition, lysosome related gene ATP6V1E1 and immune response related genes (IL2RG, OSM, EVI2B TNFRSF1A, CXCR4, STAT5A) were significantly correlated with Aβ or Tau pathology. Finally, receiver operating characteristic (ROC) analysis revealed that ATP6V1E1 showed high‐diagnostic potential for AD.

Conclusion

Taken together, our data identified the main pathological pathways in AD progression, particularly the systemic dysregulation of the immune response, and provided peripheral biomarkers for AD diagnosis.
Motor problems in autism: Co‐occurrence or feature?
Authors: Miller Haylie L. , Licari Melissa K. , Bhat Anjana , Aziz‐Zadeh Lisa S. , Van Damme Tine , Fears Nicholas E. , Cermak Sharon A. , Tamplain Priscila M.
Published: June 2023

Motor features of autism have long been acknowledged by clinicians, researchers, and community stakeholders. Current DSM‐5 and ICD‐11 guidelines allow clinicians to assign a co‐occurring diagnosis of developmental [motor] coordination disorder (DCD) for autistic individuals with significant motor problems. DCD is characterized by poor motor proficiency with an onset of symptoms in early development. Studies have shown considerable overlap in the behavioral motor features observed in autism and DCD. However, others indicate that motor problems in autism and DCD may stem from different underlying sensorimotor mechanisms. Regardless of whether autism has a unique motor phenotype or an overlap with DCD, changes need to be made in the clinical pipeline to address motor problems in autism at the stages of recognition, assessment, diagnosis, and intervention. Consensus is needed to address unmet needs in research on the etiology of motor problems in autism and their overlap with DCD, to optimize clinical practice guidelines. The development of screening and assessment tools for motor problems that are valid and reliable for use with autistic individuals is essential, and an evidence‐based clinical pipeline for motor problems in autism is urgently needed.

What this paper adds

Motor problems in autism are highly prevalent, yet underdiagnosed and poorly managed.

An evidence‐based clinical pipeline for motor problems in autism is urgently needed.
Cost‐utility of real‐time continuous glucose monitoring versus self‐monitoring of blood glucose and intermittently scanned continuous glucose monitoring in people with type 1 diabetes receiving multiple daily insulin injections in Denmark
Authors: Alshannaq Hamza , Cogswell Greg , Pollock Richard F. , Ahmed Waqas , Norman Greg J. , Lynch Peter M. , Roze Stephane
Published: June 2023

Aims

To determine the cost‐effectiveness of the Dexcom G6 real‐time continuous glucose monitoring (rt‐CGM) system compared with both the self‐monitoring of blood glucose (SMBG) and the Abbott FreeStyle Libre 1 and 2 intermittently scanned CGM (is‐CGM) devices in people with type 1 diabetes receiving multiple daily insulin injections in Denmark.

Materials and Methods

The analysis was performed using the IQVIA Core Diabetes Model, which associates rt‐CGM use with glycated haemoglobin reductions of 0.6% and 0.36% based on data from the DIAMOND and ALERTT1 trials, respectively, compared with SMBG and is‐CGM use. The analysis was performed from the payer perspective over a 50‐year time horizon; future costs and clinical outcomes were discounted at 4% per annum.

Results

The use of rt‐CGM was associated with an incremental gain of 1.37 quality‐adjusted life years (QALYs) versus SMBG. Total mean lifetime costs were Danish Krone (DKK) 894 535 for rt‐CGM and DKK 823 474 for SMBG, resulting in an incremental cost‐utility ratio of DKK 51 918 per QALY gained versus SMBG. Compared with is‐CGM, the use of rt‐CGM led to a gain of 0.87 QALYs and higher mean lifetime costs resulting in an incremental cost‐utility ratio of DKK 40 879 to DKK 34 367 per QALY gained.

Conclusions

In Denmark, the rt‐CGM was projected to be highly cost‐effective versus both SMBG and is‐CGM, based on a willingness‐to‐pay threshold of 1× per capita gross domestic product per QALY gained. These findings may help inform future policies to address regional disparities in access to rt‐CGM.
Real‐world study of ethnic differences in glycaemic control and clinical characteristics among insulin‐naïve people with type 2 diabetes initiating biphasic insulin aspart 30/70: A retrospective, observational cohort study in England
Authors: Davies Melanie J. , Alibegovic Amra Ciric , Jensen Anders Boeck , Munikrishnappa Renuka , Nordsborg Rikke Baastrup , Braae Uffe Christian
Published: June 2023

Aims

This study investigated the ethnic differences in glycaemic levels and clinical characteristics among insulin‐naïve people with type 2 diabetes (T2D) initiating biphasic insulin aspart 30/70 (BIAsp 30) in primary practice in England.

Materials and Methods

Retrospective, observational cohort study utilizing data from the Clinical Practice Research Datalink Aurum database, including White, South Asian, Black and Chinese insulin‐naïve adults with T2D, initiating BIAsp 30. The index date was that of the first BIAsp 30 prescription. Endpoints included change in glycated haemoglobin (HbA1c) and body mass index (BMI) 6 months post index.

Results

In total, 11 186 eligible people were selected (9443 White, 1116 South Asian, 594 Black, 33 Chinese). HbA1c decreased across all subgroups 6 months post index: estimated %‐point changes [95% CI of −2.32 (−2.36; −2.28) (White); −1.91 (−2.02; −1.80) (South Asian); −2.55 (−2.69; −2.40) (Black); and −2.64 (−3.24; −2.04) (Chinese)]. The BMI increased modestly 6 months post index in all subgroups [estimated changes (95% CI) kg/m2: White, 0.92 (0.86; 0.99); South Asian, 0.60 (0.41; 0.78); Black, 1.41 (1.16; 1.65); and Chinese, 0.32 (−0.67; 1.30)]. In the overall population, hypoglycaemic event rates increased from 0.92 events per 100 patient‐years before the index to 3.37 events per 100 patient‐years post index; event numbers were too low to be analysed by subgroup.

Conclusions

Among insulin‐naïve people with T2D initiating BIAsp 30, clinically meaningful HbA1c reductions in all ethnicities were observed. Some ethnic groups had larger reductions than others, but differences were small. In all groups, small BMI increases were seen, with small differences observed between groups. Hypoglycaemia rates were low.
Discourse Ethics: A Pedagogical Policy for Promoting Democratic Virtues
Authors: Nunner‐Winkler Gertrud
Published: June 2023

The guidelines followed by many educational boards recommend behavioristic practices for dealing with student discipline; however, Lawrence Kohlberg's idea of organizing schools as “just communities” suggests a more promising approach. It translates to the school context the core principle of Habermas's discourse ethics: those norms to which all concerned agree are valid. In such democratically organized schools, students engage in less violence and take greater responsibility for safeguarding each other's welfare. Public debates about rules and handling transgressions generate knowledge regarding shared norms, promote role‐taking abilities, and foster ego‐syntonic commitment to democratic values. Such participatory experiences may contribute to constituting ego identity. Whereas identity politics relies on particularistic affiliations and emphasizes demarcations between social groups, ego identity is based on a commitment to universal moral values. This commitment allows individuals to develop and sustain a sense of coherence, continuity, and uniqueness, and it fosters democratic cooperation and social cohesion. In this article, Gertrud Nunner‐Winkler provides empirical support for these claims.
A concise study of acetazolamide in glucose transporter type 1 deficiency (G1D) epilepsy
Authors: Málaga Ignacio , Avila Adrian , Primeaux Sharon , Park Jason Y. , Pascual Juan M.
Published: June 2023

Epilepsy constitutes the most common paroxysmal manifestation of glucose transporter type 1 deficiency (G1D) and is generally considered medication‐refractory. It can also prove therapeutic diet‐resistant. We examined acetazolamide effects in G1D motivated by several longstanding and recent observations: First, the electrographic spike‐waves characteristic of absence seizures often resemble those of G1D and, since the 1950s, they have occasionally been treated successfully with acetazolamide, well before G1D was segregated from absence epilepsy as a distinct syndrome. Second, synaptic inhibitory neuron failure characterizes G1D and, in other experimental models, this can be ameliorated by drugs that modify cellular chloride gradient such as acetazolamide. Third, acetazolamide potently stimulates model cell glucose transport in vitro. Seventeen antiepileptic drug or therapeutic diet‐refractory individuals with G1D treated with acetazolamide were thus identified via medical record review complemented by worldwide individual survey. Acetazolamide was tolerated and decreased seizures in 76% of them, with 58% of all persons studied experiencing seizure reductions by more than one‐half, including those who first manifested myoclonic‐astatic epilepsy or infantile spams. Eighty‐eight percent of individuals with G1D continued taking acetazolamide for over 6 months, indicating sustained tolerability and efficacy. The results provide a novel avenue for the treatment and mechanistic investigation of G1D.
EnLEFD‐DM: Ensemble Learning based Ethereum Fraud Detection using CRISP‐DM framework
Authors: Pahuja Lavina , Kamal Ahmad
Published: June 2023

Cryptocurrencies continue to captivate businesses and investors despite market fluctuations. The number of crypto users has risen rapidly in the last few years, and alarmingly, many appear to be unaware of the risks involved. These risks aren't confined to market hazards but include very sophisticated cybercrimes related to cryptocurrencies. As cryptocurrencies have become a breeding ground for a variety of cybercrimes, resulting in enormous financial losses, it hinders user adoption limiting the utility of blockchain technology. It has become crucial to spot such scams and devise intelligent techniques to make this technology safer for investors. This paper proposes a classification model based on the Cross Industry Standard Process for Data Mining (CRISP‐DM) framework to identify fraudulent transactions over the Ethereum blockchain. Its contribution is multi‐faceted; first, the available imbalanced Ethereum dataset has been balanced to enhance the accuracy of the classification model. Second, the correlation‐based feature selection technique has been applied to retain the best discriminating features. Thirdly, an effective machine learning‐based ensemble classification model has been adopted for the identification of fraudulent transactions over the Ethereum network. A comparative analysis of 10 machine learning techniques has been presented consisting of both individual and ensemble classifiers. Evaluated outcomes show that ensemble classifiers appear to yield better performance measures over individual classifiers, and among all, the LightGbm classifier outperformed with 99.2% accuracy. Further, extensive experiments indicate that the proposed method outperforms the state‐of‐the‐art method when applied to a similar dataset.