bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of the SARS-CoV-2 spike protein revealed that blocked receptor-binding domain antigenicity decreases the production of neutralizing antibodies in vivo
Authors: Mei Ya-Fang , Zhang Qian , Hammond Maria , Song Jie , Fang Zongwei , Zhao Hongxing , Landgren Marene 
Published: February 2023

AbstractThe identification of SARS-CoV-2 spike protein distribution and function in target cells has raised concerns about its possible impacts on vaccine efficacy and pathogenic effect in host cells. Thus, a better understanding of such consequences is necessary. In this study, we studied the biological characteristics of six variants of SARS-CoV-2 in A549 and HEK293 cells using four different technologies. The results showed that compared to the other fragments, the full-length spike protein exhibited the highest expression on the cell surface and was detectable in the cell supernatant, cytoplasm, and nucleus. Except for the cell surface, the S1 subunit generally expressed higher than the full-length spike protein. RBD and S2 subunits were expressed in the cytoskeleton. The SS-RBD peptide, which consists of a 19-amino acid signal peptide sequence (SS)-linked RBD, exhibited the highest expression in the cell supernatant among all other studied peptides. The SS positively enhanced the expression, migration, and secretion of SS-RBD from the cytoskeleton to the supernatant. Importantly, the FACS assay results showed that neutralizing antibodies (NAbs) could recognize SS-RBD but not RBD in the transfected cells, suggesting that RBD was tightly bound by ACE2 in HEK293 cells. In contrast, the antigenicity of the RBD in the spike protein was revealed and efficiently monitored only by 6-His-tag mAbs. Thus, our findings demonstrated that ACE2 blocks crucial immunogenic epitopes of the RBD, and the full-length spike protein mainly induces non-neutralizing antibodies in vivo. Therefore, we suggest that reducing ACE2 binding affinity and exposing the immunogenicity of the RBD on the spike protein is imperative for improving vaccine efficacy and generating new SARS-CoV-2 mRNA vaccines.
Comparative gene regulatory network analysis in Alzheimer’s disease and major depressive disorder identifies shared core regulatory circuits
Authors: Puype Hanne , Deschildre Joke , Vermeirssen Vanessa 
Published: February 2023

AbstractAlzheimer’s disease and major depressive disorder are prevalent, devastating conditions with limited treatment options. Recent insights suggest that despite distinct phenotypes, these disorders share similar processes such as neuroinflammation. However, the extent of overlapping biological processes and their underlying molecular mechanisms remain to be elucidated. Therefore, we adopted a computational systems biology approach to compare regulatory programs in the prefrontal cortex of both disorders. Leveraging publicly available RNA sequencing data on different human cohorts, both at bulk and single-cell level, and using diverse computational methodologies, we inferred gene regulatory networks, which model the molecular interactions between transcription factors and their target genes, and characterized cell-type-specific regulatory programs and biological pathways. We identified core regulatory circuits shared in both disorders, including transcription factors that play a pivotal role in microglial activation such as IKZF1, IRF8, RUNX1 and SPI1. Most of these transcription factors had a reported role in Alzheimer’s, but not in depression. We found several common pathways such as microglial activation, but also more disease-specific pathways. Through orthogonal data analysis, we were able to validate several of the predicted regulatory interactions in Alzheimer’s disease and major depressive disorder. In summary, our work revealed neuroinflammation and microglial activation in both diseases, under the control of shared core regulatory circuits. The potential relevance of these transcription factors and genes warrants additional investigation, especially in depression, offering possible novel therapeutic opportunities.
New estimates indicate that males are not larger than females in most mammals
Authors: Tombak Kaia J. , Hex Severine B. S. W. , Rubenstein Daniel I. 
Published: February 2023

AbstractSexual size dimorphism (SSD) has motivated a large body of research on mammalian mating strategies and sexual selection. Despite some contrary evidence, the narrative that larger males are the norm in mammals – upheld since Darwin’sDescent of Man– still dominates today, supported by meta-analyses that use crude measures of dimorphism and taxonomically-biased data. With newly-available datasets and primary sources reporting sex-segregated means and variances in adult body mass, we estimated statistically-determined rates of SSD in mammals, sampling taxa by their species richness at the family level. Our analyses of >400 species indicate that although males tend to be larger than femaleswhendimorphism occurs, males arenotlarger in most mammals, and suggest a need to revisit other assumptions in sexual selection research.One-Sentence SummaryTaxonomically-balanced estimates of rates of sexual size dimorphism in mammals refute the ‘larger males’ narrative.
Multicellular factor analysis of single-cell data for a tissue-centric understanding of disease
Authors: Ramirez Flores Ricardo O. , Lanzer Jan D. , Dimitrov Daniel , Velten Britta , Saez-Rodriguez Julio 
Published: February 2023

AbstractSingle-cell atlases across conditions are essential in the characterization of human disease. In these complex experimental designs, patient samples are profiled across distinct cell-types and clinical conditions to describe disease processes at the cellular level. However, most of the current analysis tools are limited to pairwise cross-condition comparisons, disregarding the multicellular nature of disease processes and the effects of other biological and technical factors in the variation of gene expression. Here we propose a computational framework for an unsupervised analysis of samples from cross-condition single-cell atlases and for the identification of multicellular programs associated with disease. Our strategy, that repurposes multi-omics factor analysis, incorporates the variation of patient samples across cell-types and enables the joint analysis of multiple patient cohorts, facilitating integration of atlases. We applied our analysis to a collection of acute and chronic human heart failure single-cell datasets and described multicellular processes of cardiac remodeling that were conserved in independent spatial and bulk transcriptomics datasets. In sum, our framework serves as an exploratory tool for unsupervised analysis of cross-condition single-cell atlas and allows for the integration of the measurements of patient cohorts across distinct data modalities, facilitating the generation of comprehensive tissue-centric understanding of disease.Graphical Abstract
A novel adjuvant formulation induces robust Th1/Th17 memory and mucosal recall responses in Non-Human Primates
Authors: Woodworth Joshua S , Contreras Vanessa , Christensen Dennis , Naninck Thibaut , Kahlaoui Nidhal , Gallouët Anne-Sophie , Langlois Sébastien , Burban Emma , Joly Candie , Gros Wesley , Dereuddre-Bosquet Nathalie , Morin Julie , Olsen Ming Liu , Rosenkrands Ida , Stein Ann-Kathrin , Wood Grith Krøyer , Follmann Frank , Lindenstrøm Thomas , LeGrand Roger , Pedersen Gabriel Kristian , Mortensen Rasmus 
Published: February 2023

AbstractAfter clean drinking water, vaccination is the most impactful global health intervention. However, development of new vaccines against difficult-to-target diseases is hampered by the lack of diverse adjuvants for human use. Of particular interest, none of the currently available adjuvants induce Th17 cells. Here, we develop and test an improved liposomal adjuvant, termed CAF®10b, that incorporates a TLR-9 agonist. In a head-to-head study in non-human primates (NHPs), immunization with antigen adjuvanted with CAF®10b induced significantly increased antibody and cellular immune responses compared to previous CAF® adjuvants, already in clinical trials. This was not seen in the mouse model, demonstrating that adjuvant effects can be highly species specific. Importantly, intramuscular immunization of NHPs with CAF®10b induced robust Th17 responses that were observed in circulation half a year after vaccination. Furthermore, subsequent instillation of unadjuvanted antigen into the skin and lungs of these memory animals led to significant recall responses including transient local lung inflammation observed by Positron Emission Tomography-Computed Tomography (PET-CT), elevated antibody titers, and expanded systemic and local Th1 and Th17 responses, including >20% antigen-specific T cells in the bronchoalveolar lavage. Overall, CAF®10b demonstrated an adjuvant able to drive true memory antibody, Th1 and Th17 vaccine-responses across rodent and primate species, supporting its translational potential.
Computational Modelling of Immune Interaction and Epidermal Homeostasis in Psoriasis
Authors: Paramalingam Dinika , Li Bowen , Reynolds Nick J. , Zuliani Paolo 
Published: February 2023

AbstractPsoriasis is an incurable chronic inflammatory skin disease characterised by immune cytokine-stimulated epidermal hyperproliferation. This results in the skin becoming red with scaly plaques that can appear anywhere on the body, decreasing the quality of life for patients. Previous modelling studies of psoriasis have been limited to 2D models and lacked cell-cell interactions. We have developed a 3D agent-based model of epidermal cell dynamics to gain insights into how immune cytokine stimuli induces hyperproliferation in psoriasis to better understand disease formation and structural changes. Three main keratinocytes, stem, transit-amplifying (TA), differentiated and T cells, are modelled with proliferation and division governed by various nutrients and immune cytokines. Each cell has a set of attributes (growth rate, division probability, position, etc) whose values are governed by processes such as monod-based cellular growth model, probability-based division based on calcium and cytokine concentration and various forces to form the epidermal layers. The model has 2 steady states, healthy (non-lesional) and psoriatic (lesional) skin. Transition from healthy to psoriatic state is triggered by a temporary cytokine stimulus which causes hyperproliferation to occur, a hallmark of psoriasis. This results in the deepening of rete ridges and thickening of the epidermal structure. Model outputs has been validated against population ratios of stem, TA, differentiated, and T cells, cell cycle and turnover times in vivo. The model simulates the structural properties of epidermis, including layer stratification, formation of wave-like rete ridges, change in epidermal height and length of rete ridges from healthy to psoriasis. This has provided some insights on the complex spatio-temporal changes when transitioning between the 2 steady states and how a shot of temporary cytokine stimulus can induce different severity of psoriasis and alters proliferation between healthy and psoriatic skin in line with known literature. This provides the basis to study different cytokine simulation variations of psoriasis development and tracking of cell proliferation in the lab. It also provides a baseline to model the effects of psoriasis treatments such as narrowband-ultraviolet B (NB-UVB) or biologics and predict potential treatment outcomes for patients.
Human Dermal Fibroblast Subpopulations and Epithelial Mesenchymal Transition Signals in Hidradenitis Suppurativa Tunnels are Normalized by Spleen Tyrosine Kinase Antagonism in Vivo
Authors: Flora A , Jepsen R , Kozera EK , Woods JA , Cains GD , Radzieta M , Jensen SO , Malone M , Frew JW 
Published: February 2023

ABSTRACTHidradenitis Suppurativa is a chronic inflammatory disease of which the pathogenesis is incompletely understood. Dermal fibroblasts have been previously identified as a major source of inflammatory cytokines, however information pertaining to the characteristics of subpopulations of fibroblasts in HS remains unexplored. Using in silico-deconvolution of whole-tissue RNAseq, Nanostring gene expression panels and confirmatory immunohistochemistry we identified fibroblast subpopulations in HS tissue and their relationship to disease severity and lesion morphology. Gene signatures of SFRP2+ fibroblast subsets were increased in lesional tissue, with gene signatures of SFRP1+ fibroblast subsets decreased. SFRP2+ and CXCL12+ fibroblast numbers, measured by IHC, were increased in HS tissue, with greater numbers associated with epithelialized tunnels and Hurley Stage 3 disease. Pro-inflammatory CXCL12+ fibroblasts were also increased, with reductions in SFRP1+ fibroblasts compared to healthy controls. Evidence of Epithelial Mesenchymal Transition was seen via altered gene expression of SNAI2 and altered protein expression of ZEB1, TWIST1, Snail/Slug, E-Cadherin and N-Cadherin in HS lesional tissue. The greatest dysregulation of EMT associated proteins was seen in biopsies containing epithelialized tunnels. The use of the oral Spleen tyrosine Kinase inhibitor Fostamatinib significantly reduced expression of genes associated with chronic inflammation, fibroblast proliferation and migration suggesting a potential role for targeting fibroblast activity in HS.
Corporate collaborations, decarbonization and equity value creation
Authors: Schellhorn Carolin 
Published: February 2023

Purpose
Opportunities for shareholder value creation from deep decarbonization in fossil fuel and related industries may be unlocked with a permanent change in corporate governance practices. The purpose of this study is to highlight the conceptual links between corporate collaborations, decarbonization and equity value creation to enable the large-scale reallocation of funds necessary to halve carbon emissions by the end of this decade.

Design/methodology/approach
Consistent with shareholder value maximization, the author uses the constant dividend growth framework to show that a permanent change in corporate governance practices can impact expectations of future cash flows and required rates of return. This study includes a simulation to explore how perpetual corporate collaborations on decarbonization that influence the key equity value drivers can add value to the equity of collaborative firms.

Findings
Perpetual corporate collaborations with key stakeholders focused on equity value drivers hold great potential for accelerating the reallocation of funds to low-carbon assets. Simulation results suggest that relatively small changes, especially in required rates of return, may result in substantial increases in equity values for collaborative leaders in deep decarbonization.

Originality/value
This study identifies new sources of shareholder value from long-term corporate collaborations with key stakeholders on deep decarbonization. A collaborative focus on important equity value drivers can attract capital also to hard-to-abate industries and initiate sharp cuts in carbon emissions. Corporate governance practices, thus, reformed render shareholder value creation incentive compatible with rapidly decarbonizing global supply chains, making it possible to meet climate action goals by 2030.
Does ownership concentration matter for the relationship between CEO characteristics and real earnings management: evidence from Jordan
Authors: Alhmood Mohammad , Shaari Hasnah , Al-Dhamari Redhwan , Sani Armaya’U Alhaji 
Published: February 2023

PurposeThe current research inspects the moderation role of ownership concentration on chief executive officer (CEO) characteristics and real earnings management (REM) relationship in Jordan.Design/methodology/approachDriscoll–Kraay regressions were run using data from 348 firm-year observations for companies listed on the Amman Stock Exchange between 2013 and 2018.FindingsDriscoll–Kraay regressions demonstrate that CEO experience, tenure and political connections improve REM practices. Ownership concentration diminishes and limits REM practices when combined with CEO experience, tenure and political connections, since all three have a negative and significant link with REM.Research limitations/implicationsInitial constraints include the study’s lack of generalisability due to a small number of CEO-related parameters. Second, critics of the ideal model for judging EM have a foreseeable flaw. No generally accepted model is perfect.Practical implicationsThis study’s conclusions are crucial for industry participants, including companies, policymakers, investors and the general public. These findings will help investors, practitioners and regulators understand that businesses with significant ownership concentrations and experienced CEOs have superior earnings and low REM practises.Social implicationsThe findings of this study have an optimistic impact on the existing body of knowledge. The current literature has yet to properly inspect the moderation role that ownership concentration has on the connotation between CEO characteristics and EM.Originality/valueDespite several research studies in both developed and developing nations, ownership concentration has been almost virtually neglected. The current study could fill a hole in earlier research, rendering it a novel study.
Nurturing innovative culture in a healthcare organisation – Lessons from a Swedish case study
Authors: Andersson Thomas , Linnéusson Gary , Holmén Maria , Kjellsdotter Anna 
Published: February 2023

PurposeHealthcare organisations are often described as less innovative than other organisations, since organisational culture works against innovations. In this paper, the authors ask whether it has to be that way or whether is possible to nurture an innovative culture in a healthcare organisation. The aim of this paper is to describe and analyse nurturing an innovative culture within a healthcare organisation and how culture can support innovations in such a healthcare organisation.Design/methodology/approachBased on a qualitative case study of a healthcare unit that changed, within a few years, from having no innovations to repeatedly generating innovations, the authors describe important aspects of how innovative culture can be nurtured in healthcare. Data were analysed using inductive and deductive analysis steps.FindingsThe study shows that it is possible to nurture an innovative culture in a healthcare organisation. Relationships and competences beyond healthcare, empowering structures and signalling the importance of innovation work with resources all proved to be important. All are aspects that a manager can influence. In this case, the manager's role in nurturing innovative culture was very important.Practical implicationsThis study highlights that an innovative culture can be nurtured in healthcare organisations and that managers can play a key role in such a process.Originality/valueThe paper describes and analyses an innovative culture in a healthcare unit and identifies important conditions and strategies for nurturing innovative culture in healthcare organisations.
The control of tax corruption: evidence from nonfungible token market in China
Authors: Rahman Jahidur , Jin Yahan 
Published: February 2023

Purpose
In 2021, nonfungible token (NFT) has emerged and grown as a new digital asset and became a carrier for cryptocurrency holders in China. NFT opens the door of the digital world for creators’ rights and the realization of economic interests. However, potential problems such as money laundering, terrorist financing and tax avoidance risks have increased in China due to the lack of regulations. As tax control is an important tool used by the government to adjust the economy and market, this study aims to investigate the future market capitalization of NFT and provide value orientations to control the NFT market in China with a tax control approach based on the positive experience of other countries.

Design/methodology/approach
In this study, least squares and expert estimation are applied to predict the future market capitalization based on the global market, which can provide an understanding of the current NFT market and the significance of its tax control. In addition, the tax control and interpretation of Chinese taxation institutions and structures are also explored.

Findings
Results include the probable tax structure or policy that national institutions can carry out over different transactions. Conclusions show that introducing tax control to regulate and monitor the rise of state revenue and decline of illegal financing activities. Establishing tax control in the Chinese NFT market can provide a centralized guarantee to ensure the safety and legality of transactions and enable further progress.

Originality/value
This study puts forward new ideas on the future development of nonprofitable tokens based on blockchain technology from the perspective of taxation in China.
Occupational self-efficacy, job crafting and job satisfaction in newcomer socialization: a moderated mediation model
Authors: Yang Yingxi , Zhou Yong , Peng Siyi , Li Hairong 
Published: February 2023

PurposeDrawing on job crafting theory and the social cognitive theory of work satisfaction, the purpose of this study is to examine the impacts of task, relational and cognitive crafting on job satisfaction and how occupational self-efficacy (OSE) and hierarchical organizational culture affect the execution and outcome of job crafting behaviors.Design/methodology/approachData were collected at four time points among Chinese media professionals (N = 198) during three consecutive months. Regression analysis and the bootstrap method were used for hypothesis testing.FindingsOnly cognitive crafting was found to mediate the positive relationship between OSE and job satisfaction. In a hierarchical organizational culture, the positive effects of OSE on task, relational and cognitive crafting became stronger, while the effect of task crafting on job satisfaction became negative. The authors also identified a conditional negative effect of OSE on job satisfaction via task crafting. The mediating effect of cognitive crafting was consistent despite the levels of hierarchical culture.Practical implicationsTo retain new hires, organizations should look for efficacious individuals and encourage the individuals to cognitively craft individuals' jobs, especially in a hierarchical culture. Moreover, job crafting interventions should be carefully designed in this type of culture.Originality/valueThis research identifies the three dimensions of job crafting as mediators that link OSE to job satisfaction and reveals the role of hierarchical culture in moderating these relationships.