bluuebunny/crossref_metadata_2025 huggingface dataset:
TIPRL1 and its ATM-dependent phosphorylation promote radiotherapy resistance in head and neck cancer
Authors: Cokelaere Célie , Dok Rüveyda , Cortesi Emanuela E. , Zhao Peihua , Sablina Anna , Nuyts Sandra , Derua Rita , Janssens Veerle
Published: September 2023

TIPRL1 (target of rapamycin signaling pathway regulator-like 1) is a known interactor and inhibitor of protein phosphatases PP2A, PP4 and PP6 – all pleiotropic modulators of the DNA Damage Response (DDR). Here, we describe a new role for TIPRL1 in the radiotherapy (RT) response of Head and Neck Squamous Cell Carcinoma (HNSCC). TIPRL1 expression was found increased in tumor versus non- tumor tissue, with high tumoral TIPRL1 expression associating with lower locoregional control and decreased survival of RT-treated patients. TIPRL1 deletion in HNSCC cells resulted in increased RT sensitivity, a faster but prolonged cell cycle arrest, increased micronuclei formation and an altered proteome-wide DDR. Upon irradiation, ATM phosphorylates TIPRL1 at Ser265, contributing to TIPRL1-mediated RT resistance. Mass spectrometry analysis identified DNA-PKcs, RAD51 and nucleosomal histones as novel TIPRL1 interactors. Histone binding, although stimulated by RT, was adversely affected by TIPRL1 Ser265 phosphorylation. Our findings underscore a clinically relevant role for TIPRL1 and its ATM-dependent phosphorylation in RT resistance through modulation of DNA damage checkpoint activation and repair.
Exploring The Role Of Isolation By Distance, Isolation By Environment, And Hybridization InCampylorhynchusWrens Along A Precipitation Gradient In Western Ecuador
Authors: Montalvo Luis Daniel , Kimball Rebecca T. , Austin James , Robinson Scott
Published: September 2023

Climate variability can cause genetic and phenotypic diversity within species, which affects the evolution of biodiversity. A balance between gene flow and selection maintains changes in the frequency of genetic and phenotypic variants along an environmental gradient. In this study, we investigated a hybrid zone in western Ecuador involving two species of wrens (Aves: Troglodytidae), Campylorhynchus zonatus and C. fasciatus, and their admixed populations. We hypothesized that isolation by distance (IBD) and different ecological preferences, isolation by environment (IBE), result in limited dispersal between populations along the precipitation gradient in western Ecuador.

We asked two main questions: (1) What is the relative contribution of IBD and IBE to patterns of genetic differentiation of these species along the environmental gradient in western Ecuador? And (2) Is there evidence of genetic admixture and introgression between these taxa in western Ecuador? We analyzed 4,409 SNPs from the blood of 112 individuals sequenced using ddRadSeq. The most likely clusters ranged from K=2-4, corresponding to categories defined by geographic origins, known phylogenetics, and physical or ecological constraints. Evidence for IBD was strong across all models, and evidence for IBE was less strong but still significant for annual mean precipitation and precipitation seasonality. We observed gradual changes in genetic admixture between C. f. pallescens and C. zonatus along the environmental gradient. Genetic differentiation of the two populations of C. f. pallescens could be driven by a previously undescribed potential physical barrier near the center of western Ecuador. Lowland habitats in this region may be limited due to the proximity of the Andes to the coastline, limiting dispersal and gene flow, particularly among dry-habitat specialists. We do not propose taxonomic changes, but the admixture observed in C. f. pallescens suggests that this described subspecies could be a hybrid between C. z. brevirostris and C. fasciatus, with different degrees of admixture along western Ecuador and northwestern Peru. This study contributes to the knowledge of avian population genomics in the tropics.
The expression profile and tumorigenic mechanisms of CD97 (ADGRE5) in glioblastoma render it a targetable vulnerability
Authors: Ravn-Boess Niklas , Roy Nainita , Hattori Takamitsu , Bready Devin , Donaldson Hayley , Lawson Christopher , Lapierre Cathryn , Korman Aryeh , Rodrick Tori , Liu Enze , Frenster Joshua D. , Stephan Gabriele , Wilcox Jordan , Corrado Alexis D. , Cai Julia , Ronnen Rebecca , Wang Shuai , Haddock Sara , Sabio Ortiz Jonathan , Mishkit Orin , Khodadadi-Jamayran Alireza , Tsirigos Aris , Fenyö David , Zagzag David , Perna Fabiana , Jones Drew R. , Possemato Richard , Koide Akiko , Koide Shohei , Park Christopher Y. , Placantonakis Dimitris G.
Published: September 2023

Glioblastoma (GBM) is the most common and aggressive primary brain malignancy. Adhesion G protein-coupled receptors (aGPCRs) have attracted interest for their functional role in gliomagenesis and their potential as treatment targets. To identify therapeutically targetable opportunities among aGPCR family members in unbiased fashion, we analyzed expression levels of all aGPCRs in GBM and non-neoplastic brain tissue. Using bulk and single cell transcriptomic and proteomic data, we show that CD97 (ADGRE5), an aGPCR previously implicated in GBM pathogenesis, is the most promising aGPCR target in GBM, by virtue of its abundance in all GBM tumors and itsde novoexpression profile in GBM compared to normal brain tissue and neural progenitors. CD97 knockdown or knockout significantly reduces the tumor initiation capacity of patient-derived GBM cultures (PDGC)in vitroandin vivo. Transcriptomic and metabolomic data from PDGCs suggest that CD97 promotes glycolytic metabolism. The oncogenic and metabolic effects of CD97 are mediated by the MAPK pathway. Activation of MAPK signaling depends on phosphorylation of the cytosolic C-terminus of CD97 and recruitment of β-arrestin. Using single-cell RNA-sequencing and biochemical assays, we demonstrate that THY1/CD90 is the most likely CD97 ligand in GBM. Lastly, we show that targeting of PDGCs with an anti-CD97 antibody-drug conjugatein vitroselectively kills tumor cells but not human astrocytes or neural stem cells. Our studies identify CD97 as an important regulator of tumor metabolism in GBM, elucidate mechanisms of receptor activation and signaling, and provide strong scientific rationale for developing biologics to target it for therapeutic purposes.
Plasticity in plant populations may be constrained by performance costs, complex environments and weakly integrated phenotypes
Authors: Hennion Françoise , Labarrere Bastien , Renaudon Marine , Prinzing Andreas
Published: September 2023

Background and AimsOne response of plants to climate warming is plasticity of traits, but plasticity might come at a cost and might be limited by the integration among traits or by simultaneous shift of another environmental condition such as shading. Empirical studies treating simultaneously such costs and limitations of plasticity across populations or maternal lineages within species, and how they depend on the environmental context remain few.

MethodsWe studied three plant species from the sub-Antarctic, a region currently facing one of the fastest warming worldwide. For multiple populations or maternal lineages we identified (i) plasticity by exposing seeds from a given source population to different temperature and light treatments, (ii) performance (photosynthesis or morphological performance) and (iii) morphological integration of traits in young plants.

Key ResultsWe found that plants from more plastic source populations performed poorly. Plants from more integrated source populations were more plastic. Exposure to shade rendered plants less plastic to a warming trend. Moreover, simultaneous shading and warming, rather thansoleshading orsolewarming, reduced plant performance.

ConclusionsOur results suggest that phenotypic integration of intraspecific lineages surprisingly might favour rather than limit plasticity. However, our results also suggest that plasticity in response to climate warming may be limited by parallel increase in shading from other plants including competitors, and itself does not ensure success due to induced performance costs.
Genetically mediated associations between chronotype and neuroimaging phenotypes in the UK Biobank: a Mendelian randomisation study
Authors: Williams John A. , Russ Dominic , Bravo-Merodio Laura , Gkoutos Georgios , Bellgrove Mark A. , Bagshaw Andrew P. , Chechlacz Magdalena
Published: September 2023

Chronotype impacts numerous physiological and disease traits, from metabolic syndrome to schizophrenia. The suprachiasmatic nucleus (SCN) maintains transcriptional-translational feedback loop (TTFL) which acts as a central chronobiological pacemaker, regulating 24-hour cycles throughout the human body. However, each tissue maintains its own peripheral clock, and both endogenous hormones and neurotransmitters and exogenous environmental cues regulate the SCN’s central clock. The extent to which brain regions outside the SCN influence the core TTFL is unknown. Here, we investigated how genetic variability affecting brain regions outside the SCN may indirectly influence chronotype, using Mendelian randomization and causal inference. We performed genome wide association studies (GWAS) based on image derived phenotypes (IDPs) from neuroimaging data (grey matter volume, thickness and surface area, microstructural white matter measures; 42,062 participants), and additionally for sleep duration and morning/evening chronotype (361,739 participants). Significant, single nucleotide polymorphisms (SNPs) associating with each phenotype were entered into 2-sample Mendelian randomization performed using inverse-variance weighted methods (exposure versus outcome): 1) chronotype versus each IDP, 2) sleep versus each IDP and 3) each IDP versus chronotype. Subsequently, we investigated genes where significant instrumental SNPs were located for circadian periodic cycling, interaction with TTFL genes in common biological pathways (genetic, physical, or functional interaction), and enrichment of traits from UK Biobank and GWAS Catalogs. We found three associations with chronotype (morning/evening diurnal preference) outside the SCN based on genetically predicted (FAM76B, DENND1A, CDH11) regional differences in brain volume. Specifically, genetically predicted lower inferior temporal gyrus volume linked to morning phenotype, while lower volume of the superior parietal lobule and angular gyrus linked to evening preference. In addition, evening chronotype exposure influenced superior temporal gyrus volume, and both increased sleep duration and evening chronotype influenced thalamic volume. We conclude that genetically mediated associations between chronotype and brain regions outside SCN exist suggesting novel zeitgeber mechanisms.
Changes in the Dopaminergic circuitry and Adult Neurogenesis linked to Reinforcement Learning in Corvids
Authors: Parishar Pooja , Rajagopalan Madhumita , Iyengar Soumya
Published: September 2023

The caudolateral nidopallium (NCL, an analogue of the prefrontal cortex) is known to be involved in learning, memory, and discrimination in crows, whereas the involvement of other brain regions in these phenomena are unknown. However, recent studies on pigeons have demonstrated that besides NCL, basal ganglia-thalamocortical loops connected to this region play are also crucial for learning. The present study demonstrates that besides NCL, other parts of the caudal nidopallium (NC), avian basal ganglia, and intriguingly, vocal control regions in house crows (Corvus splendens), are involved in visual discrimination. We have also found that training on the visual discrimination task can be correlated to neurite pruning in mature dopaminoceptive neurons and immature doublecortin-positive neurons in the NC of house crows. Furthermore, there is an increase in the incorporation of new neurons throughout NC and the medial striatum which can also be linked to learning. For the first time, our results demonstrate that a combination of structural changes in mature and immature neurons and adult neurogenesis are linked to learning in corvids.
Rewiring of the TCR signalosome in natural intestinal Intraepithelial T lymphocytes drives non-deletional tolerance
Authors: Watt Harriet J. , Chawla Amanpreet Singh , Lamoliatte Frederic , Pryde Sara , Knatko Elena , Rasmussen Kasper D. , Bending David , Swamy Mahima
Published: September 2023

Intraepithelial T lymphocytes (T-IEL) are a large population of cytotoxic T cells that protect the small intestinal epithelium against pathogens. Based on ontogeny, T-IEL can be categorized into two major subsets: induced and natural. Natural T-IEL are agonistically selected in the thymus on self-antigens before migrating directly to the small intestine. Despite having self-reactive T cell antigen receptors (TCR), natural T-IEL are maintained in a tolerized state in the gut by unknown mechanisms. We therefore investigated TCR signaling in T-IEL using multiplexed fluorescent cell barcoding, phosphoproteomics and TCR signaling reporter mouse models, which revealed that TCR signaling is intrinsically suppressed in natural, but not induced, T-IEL. Unexpectedly, we discover that this cell intrinsic suppression was mediated through altered TCR signalosome components. Specifically, downregulation of the key signaling adaptor, Linker for activation of T cells (LAT) during thymic selection is a vital checkpoint for the development and tolerization of natural IELs. Thus, TCR signaling is rewired in self-reactive natural T-IEL to promote tolerance and prevent inappropriate inflammation in the gut.

One sentence summary

Self-reactive natural intestinal intraepithelial T lymphocytes are developmentally tolerized by rewiring the T cell antigen receptor signaling pathway through the downregulation of the adaptor protein, LAT.
Approaches to measuring language lateralisation: an exploratory study comparing two fMRI methods and functional transcranial Doppler ultrasound
Authors: Bishop D. V.M. , Woodhead Z. V. J. , Watkins K. E.
Published: September 2023

In this exploratory study we compare and contrast two methods for deriving a laterality index (LI) from functional magnetic resonance imaging (fMRI) data: the weighted bootstrapped mean from the widely-used Laterality Toolbox (toolbox method), and a novel method that uses subtraction of activations from homologous regions in left and right hemisphere to give an array of difference scores (mirror method). Data came from 31 individuals who had been selected to include a high proportion of people with atypical laterality when tested with functional transcranial Doppler ultrasound (fTCD), and who had fMRI data for two tasks, word generation and semantic matching, which were selected as likely to activate different brain regions. In general, the mirror method gave better agreement with fTCD laterality than the toolbox method, both for individual regions of interest, and for a large region corresponding to the middle cerebral artery. LI estimates from this method had much smaller CIs than those from the toolbox method; with the mirror method, most participants were reliably lateralised to left or right, whereas with the toolbox method, a higher proportion were categorised as bilateral (i.e. the CI for the LI spanned zero). Reasons for discrepancies between fMRI methods are discussed: one issue is that the toolbox method averages the LI across a wide range of thresholds. Furthermore, examination of task-related t-statistic maps from the two hemispheres showed that language lateralisation is evident in regions characterised by deactivation, and so key information may be lost by ignoring voxel activations below zero, as is done with conventional estimates of the LI.
The effect of dopamine D2 receptor blockade on human motor skill learning
Authors: Taylor Eleanor M. , Curtin Dylan , Chong Trevor T-J. , Bellgrove Mark A. , Coxon James P.
Published: September 2023

Rationale:Dopamine signalling supports motor skill learning in a variety of ways, including through an effect on cortical and striatal plasticity. One neuromodulator that has been consistently linked to motor skill learning is dopamine. However, the specific role of dopamine D2 receptor in the acquisition and consolidation stages of motor learning remains unclear.

Objectives

To examine the effect of a selective D2 receptor antagonist on human motor skill acquisition and consolidation.

Methods

In this randomised, double-blind, placebo-controlled design, healthy adult men and women (N = 23) completed a sequential motor skill learning task after taking either sulpiride (800mg) or placebo. A 20-minute bout of high-intensity interval cycling exercise was included to enhance experimental effects and counteract potentially confounding sedative effects of sulpiride.

Results

Sulpiride reduced performance during motor skill acquisition relative to placebo in the first session, however this difference was abolished at the subsequent retention test. Sulpiride did not reduce consolidation of learning as expected, however it led to a reduction in speed of execution relative to placebo.

Conclusions

Our results demonstrate that neuromodulation at the dopamine D2 receptor is critical in the early acquisition of a novel motor skill. These results may have functional relevance in motor rehabilitation as reduced dopamine transmission can impact performance during initial learning and slow subsequent performance of the skill.
Hydrogen Sulfide Coordinates Glucose Metabolism Switch through Destabilizing Tetrameric Pyruvate Kinase M2
Authors: Wang Rong-Hsuan , Chen Pin-Ru , Chen Yue-Ting , Chen Yi-Chang , Chu Yu-Hsin , Chien Chia-Chen , Chien Po-Chen , Lo Shao-Yun , Wang Zhong-Liang , Tsou Min-Chen , Chen Ssu-Yu , Chiu Guang-Shen , Chen Wen-Ling , Wu Yi-Hsuan , Wang Lily Hui-Ching , Wang Wen-Ching , Lin Shu-Yi , Kung Hsing-Jien , Wang Lu-Hai , Cheng Hui-Chun , Lin Kai-Ti
Published: September 2023

Cancer cells reprogram their glucose metabolic pathway from oxidative phosphorylation toward aerobic glycolysis. Pyruvate kinase M2 (PKM2), which converts phosphoenolpyruvate (PEP) to pyruvate, is considered the rate-limiting enzyme involved in cancer glucose metabolism. By reducing PKM2 enzyme activity, cancer cells attain a greater fraction of glycolytic metabolites for macromolecule synthesis needed for rapid proliferation. Here we demonstrate that hydrogen sulfide (H2S) destabilizes PKM2 tetramer into dimer/monomer, leading to reduced PKM2 enzyme activity and an increase in the activation of nuclear transcriptional genes mediated by dimeric PKM2. Proteomic profiling of endogenous PKM2 reveals the occurrence of sulfhydration at cysteines, notably at cysteine 326. Blocking PKM2 sulfhydration at cysteine 326 through amino acid mutation stabilizes PKM2 tetramer and crystal structure further indicating that the tetramer organization of PKM2C326Sis different from the currently known T or R states, revealing PKM2C326Sas a newly identified form. The presence of a PKM2C326Smutant in cancer cells effectively rewires glucose metabolism to mitochondrial respiration, resulting in the significant inhibition of tumor growth. Collectively, PKM2 sulfhydration by H2S serves as a glucose metabolic rewiring mechanism in promoting tumorigenesis, and inhibition of PKM2 sulfhydration may be applied as a new therapeutic approach targeting cancer metabolism.

One-Sentence Summary

H2S rewires glucose metabolism by destabilizing PKM2 tetramerization majorly through sulfhydration at cysteine 326

Highlights

H2S enhances PKM2 dissociation from tetramer to dimer to facilitate dimeric PKM2 nuclear translocation.

H2S modifies PKM2 sulfhydration, notably at cysteine 326.

The crystal structure reveals PKM2C326Sas a unique tetramer conformation.

Blockage of PKM2 sulfhydration at C326 rewires cancer glucose metabolism and significantly inhibits tumor growth.
CoSMIC - A hybrid approach for large-scale, high-resolution microbial profiling of novel niches
Authors: Knafo Maor , Rezenman Shahar , Idan Tal , Elgart Michael , Dagan Shlomi , Reich Ziv , Kapon Ruti , Sade Dagan , Shental Noam
Published: September 2023

Standard microbial profiling based on 16S rRNA (16S) sequencing suffers from a lack of primer universality, primer biases and often yields low resolution. We introduce 'Comprehensive Small Ribosomal Subunit Mapping and Identification of Communities' (CoSMIC), addressing these challenges, especially in unexplored niches. CoSMIC begins with long-read sequencing of the full-length 16S gene, amplified by generic Locked Nucleic Acid primers over pooled samples, thus augmenting reference databases with novel niche-specific gene sequences. Subsequently, CoSMIC amplifies multiple non-consecutive variable regions along the gene, followed by short-read sequencing of each sample. Data from the different regions are integrated using the SMURF framework, alleviating primer biases and providing de-facto full gene resolution. Using a mock community, CoSMIC identified full-length 16S genes with significantly higher specificity and sensitivity while dramatically increasing resolution compared to standard methods. Evaluating CoSMIC across environmental samples provided higher accuracy and unprecedented resolution while detecting thousands of novel full-length 16S sequences.
Examining the role ofAcinetobacter baumanniiPlasmid Types in Disseminating Antimicrobial Resistance
Authors: Lam Margaret M. C. , Hamidian Mehrad
Published: September 2023

Acinetobacter baumanniiis a Gram-negative pathogen responsible for hospital-acquired infections with high levels of antimicrobial resistance (AMR). The spread of multidrug-resistantA. baumanniistrains, particularly those resistant to carbapenems, has become a global concern. Spread of AMR inA. baumanniiis primarily mediated by the acquisition of AMR genes through mobile genetic elements, such as plasmids. Thus, a comprehensive understanding of the role of different plasmid types in disseminating AMR genes is essential. In this study, we analysed the distribution of plasmid types, sampling sources, geographic locations, and AMR genes carried onA. baumanniiplasmids. A collection of 814 complete plasmid entries was collated and analysed. Most plasmids were identified in clinical isolates from East Asia, North America, South Asia, West Europe, and Australia.

We previously devised anAcinetobacterPlasmid Typing (APT) scheme whererep/Rep types were defined using 95% nucleotide identity and updated the scheme in this study by adding 13 novelrep/Rep types (93 types total). The APT scheme now includes 178 Rep variants belonging to three families: R1, R3, and RP. R1-type plasmids were mainly associated with global clone 1 strains, while R3-type plasmids were highly diverse and carried a variety of AMR determinants including carbapenem, aminoglycoside and colistin resistance genes. Similarly, RP-type and rep-less plasmids were also identified as important carriers of aminoglycoside and carbapenem resistance genes. This study provides a comprehensive overview of the distribution and characteristics ofA. baumanniiplasmids, shedding light on their role in the dissemination of AMR genes. The updated APT scheme and novel findings enhance our understanding of the molecular epidemiology ofA. baumanniiand provide valuable insights for surveillance and control strategies.

IMPORTANCE

A. baumanniihas emerged as a major cause of nosocomial infections, particularly in intensive care units, posing a substantial challenge to patient safety and healthcare systems. Plasmids, which carry antimicrobial resistance (AMR) genes, play a crucial role in the multidrug resistance exhibited byA. baumanniistrains, necessitating a comprehensive understanding of plasmid spread, and how to track them. This study provides important insights intoA. baumanniiplasmid epidemiology, and the extent of their role in spreading clinically significant AMR genes and how they are differentially distributed across different clones i.e. sequence types (STs) and geographical regions. These insights are important for identifying high-risk areas or clones implicated in plasmid transmission, in the context of the spread of multidrug-resistantA. baumanniistrains. It also highlights the involvement of R3-type, RP-type and rep-less plasmids in the acquisition and spread of significant AMR genes including those conferring resistance to carbapenems, aminoglycosides and colistin.
Experimental study on corrosion resistance of Zn–Al–Mg alloy coating of high-strength steel wires for bridge cables
Authors: Hu Donghui , Song Shenyou , Zhang Zongxing , Wang Linfeng
Published: September 2023

Purpose

This paper aims to figure out the conundrum that the corrosion resistance longevity of steel wires for bridge cables was arduous to meet the requirements.

Design/methodology/approach

The “two-step” hot-dip coating process for cable steel wires was developed, which involved first hot-dip galvanizing and then hot-dip galvanizing of aluminum magnesium alloy. The corrosion rate, polarization curve and impedance of Zn–6Al–1Mg and Zn–10Al–3Mg alloy-coated steel wires were compared through acetate spray test and electrochemical test, and the corrosion mechanism of Zn–Al–Mg alloy-coated steel wires was revealed.

Findings

The corrosion resistance of Zn–10Al–3Mg alloy-coated steel wires had the best corrosion resistance, which was more than seven times that of pure zinc-coated steel wires. The corrosion current of Zn–10Al–3Mg alloy-coated steel wires was lower than that of Zn–6Al–1Mg alloy-coated steel wires, whereas the capacitive arc and impedance value of the former were higher than that of the latter, making it clear that the corrosion resistance of Zn–10Al–3Mg was better than that of Zn–6Al–1Mg alloy coating. Moreover, the Zn–Al–Mg alloy-coated steel wires for bridge cables had the function of coating “self-repairing.”

Originality/value

Controlling the temperature and time of the hot dip galvanizing stage can reduce the thickness of transition layer and solve the problem of easy cracking of the transition layer in the Zn–Al–Mg alloy coating due to the Sandelin effect.
The narrative of a VET workforce shortage in Australia: reality, myth or opportunity?
Authors: Smith Erica
Published: September 2023

Purpose

The aim of the paper is to examine whether there really is a shortage of VET teachers, and if so, whether there are links to the salary offered and to the qualifications required.

Design/methodology/approach

The paper uses three main approaches to examine the narrative of a shortage of VET teachers in Australia.

Findings

There was no documented evidence of a VET teacher shortage, beyond a general perception of shortage in line with other occupations due to the post-COVID economic recovery. Salaries for VET teachers were found to compare well with other education occupations and other jobs in the economy. There was no evidence of the required qualifications deterring entry. The main concern appears to be whether VET can adequately train workers for other sectors in shortage.

Research limitations/implications

The research did not include empirical survey work and suggests that this needs to be carried out urgently.

Practical implications

The research provides evidence that will challenge current assumptions and help in the recruitment of VET teachers.

Social implications

It argues for a recognition of the importance of the VET sector beyond its function of serving industry.

Originality/value

It highlights ways to make VET teaching a more attractive proposition and to better promote its advantages.
Entrepreneurial activities, innovation, and job creation: the role of demographics and creativity as moderators
Authors: Al Alawi Abrar Mohammed , Al Kindi Kawther , Al Shukaili Abdullah , Ahmed Essia Ries
Published: September 2023

Purpose

This study aims to explore the influence of innovation in entrepreneurial activities and job creation, examine the influence of innovation in entrepreneurial activities on jobs creation and investigate the moderating influence of entrepreneurial characteristics between entrepreneurial activity, innovation and job creation.

Design/methodology/approach

The data was collected from Oman Global Entrepreneurship Monitor data 2020. Sample of 2,000 individuals was involved in entrepreneurial activities. SPSS and PLS software were used to test the structural model and research hypothesis.

Findings

The results revealed that innovation affects the level of created jobs. Entrepreneurial activity has a significant influence on innovation, jobs created and an indirect effect on jobs created through the mediating influence of innovation. All direct and indirect relationships of entrepreneurial activity and innovation with the expected jobs are insignificant. The findings demonstrate that demographics moderate the relationship between entrepreneurial activity and innovation.

Research limitations/implications

The study outcomes will be useful for policymakers to understand the innovation types in entrepreneurial activities and whether these enterprises can create future jobs.

Practical implications

The findings will help entrepreneurial ecosystems and managers to strengthen their business ventures using innovative business models.

Social implications

This research will provide decision-makers with mechanism on how better business environment will benefit stakeholders.

Originality/value

While this topic is widely investigated in developed countries, little is known about the impact of innovation on entrepreneurial activities in creating jobs in developing countries. This research contributes to entrepreneurship innovation and institutional theory literature by understanding the role of the entrepreneurship conditions framework that support the jobs creation.
Whistleblowing: interrogating the complexities of law, governance, and freedom of expression in developing nations
Authors: Adetunji Adeoye Johnson
Published: September 2023

Purpose

The purpose of this paper is to investigate the influence of the rule of law, corporate governance and freedom of expression on the effectiveness of whistleblowing initiatives. This study interrogates the effectiveness of whistleblowing as a tool in combating economic and financial crimes, in political and corporate environments where good governance and the rule of law are firmly established and enforceable and where defamation is decriminalised.

Design/methodology/approach

The author conducted a comprehensive review of relevant textbooks, focusing on legal theories and concepts related to the research topic. This study analysed scholarly journal articles to gain insights into the current debates and research gaps. The author discussed seminal court decisions that have influenced the legal landscape pertaining to the research topic and reviewed newspaper publications to understand public opinion and societal implications related to the research topic.

Findings

To ensure effective whistleblowing as a tool of gathering information in combating economic and financial crime, good governance must be promoted, supremacy of law must be upheld, freedom of expression must be safeguarded and defamation must be criminalised.

Originality/value

This paper addresses a significant gap in the literature by examining the impact of criminal libel on whistleblowing, an area that has received limited attention in previous studies. The findings of this study have significant implications for policymakers, as they shed light on importance of the rule of law, good governance, freedom of speech and decriminalisation of defamation on effective implementation of an effective whistleblowing laws and policies.
The relationship between inventory leanness and product innovation with the contingent role of market concentration
Authors: Wang Jingbin , Yao Xinyan , Zhu Xuechang
Published: September 2023

Purpose

This study aims to demonstrate the simultaneous effects between inventory leanness and product innovation, with market concentration being a moderator.

Design/methodology/approach

Using a large panel data collected from 3071 listed manufacturing enterprises from 2004 to 2021, this research employs a simultaneous system of equations via the three-stage least square method to explore the simultaneous relationship between inventory leanness and product innovation. In addition, the moderating role of market concentration is demonstrated via one four-model system.

Findings

As its core, inventory leanness positively impacts product innovation, while product innovation negatively affects inventory leanness. Moreover, there are differential impacts of the leanness of three inventory types on product innovation. Specifically, the inventory leanness of raw material negatively affects product innovation, while the inventory leanness of work-in-process and finished goods positively affect product innovation. Further, moderation analysis highlights that market concentration is a key moderator of this relationship.

Practical implications

Managers should carefully gauge the tradeoffs between inventory leanness and product innovation. Concretely, managers ought to consider the connections between inventory types and product innovation. In addition, managers are suggested to emphasis on market strategy.

Originality/value

This paper not only contributes to the current understanding of inventory leanness by verifying the impact of inventory leanness on product innovation but also investigates the simultaneous relationship between various inventory types and product innovation. Furthermore, it empirically demonstrates the moderating effect of market concentration on the relationship between inventory leanness and product innovation.
Happy people: how to nurture employee engagement in an uncertain economy
Authors: Zibbell Cara
Published: September 2023

Purpose

This paper aims to provide information about the importance of employee engagement in uncertain economic times. While the benefits of employee engagement are a widely accepted concept in theory, these efforts often suffer during an unpredictable socioeconomic environment. Often, the first things to go are the very initiatives and culture creators that drive a happy and productive workforce, which can then negatively affect business outcomes. There is a need to strike a balance between the bottom line and a well-rounded and inclusive employer relationship.

Design/methodology/approach

The paper is based upon the author’s research as well as strategies and programs they have implemented during their HR leadership career.

Findings

To improve employee engagement, it is essential to involve various departments within HR. It is important to consider all aspects of the employee experience, including members from each team, to create a well-rounded employee life cycle, even during challenging times. Committing to the methods outlined in the article and maintaining accountability will help an organization achieve lasting results.

Originality/value

The paper provides the author’s unique insights into effective strategies for employee engagement and improving the employee’s overall experience.
Work social support on hospitality employees’ career optimism and turnover intention
Authors: Bui Thi Tam , Mai Quyen Le
Published: September 2023

Purpose

This study aims to examine the effect of job insecurity and perceived work-social support on career optimism, organizational commitment and turnover intention in the hospitality industry in the post-COVID era.

Design/methodology/approach

Data collection was via an online survey of 428 hotel staff. Structural equation modeling techniques support the research model and hypothesis testing.

Findings

This study reveals that the perception of job insecurity has a strong effect on turnover intention but no significant influence on career optimism and organizational commitment. Perceived work social support plays a vital role in employees’ coping strategies in difficult work circumstances. It has positive effects on career optimism and organizational commitment.

Originality/value

The study is considered timely in verifying how the perception of job insecurity and work social support influence hospitality employees’ career optimism, organizational commitment and turnover intention as we transition to the post-pandemic era. The findings enrich the literature on job insecurity and career management through a crisis.
Evaluation of the efficacy of maintenance therapy for acne vulgaris using adapalene 0.1%/benzoyl peroxide 2.5% gel and benzoyl peroxide 2.5% gel for 24 weeks and assessment of atrophic acne scars using three‐dimensional image analysis
Authors: Tanizaki Hideaki , Hayashi Nobukazu , Abe Masatoshi
Published: September 2023

Maintenance therapy after remission of inflammation is strongly recommended in the guideline for the treatment of acne vulgaris published by the Japanese Dermatological Association. One advantage of continuing maintenance therapy is the alleviation of atrophic scarring. This study investigated the efficacy of maintenance therapy using adapalene 0.1%/benzoyl peroxide 2.5% gel and benzoyl peroxide 2.5% gel, and its effects on atrophic scarring. Overall, 126 patients were randomized to the adapalene/benzoyl peroxide group (n = 40), benzoyl peroxide group (n = 44), and control group (without maintenance treatment drugs; n = 42), and 111 of these completed a trial lasting 24 weeks. As the primary endpoint, the treatment success rate (the percentage of patients in whom the number of inflammatory lesions was maintained at ≤10) was 89.2% in the adapalene/benzoyl peroxide group, 87.5% in the benzoyl peroxide group, and 47.4% in the control group. Compared with the control group, the success rates were significantly higher in the adapalene/benzoyl peroxide and benzoyl peroxide groups (P = 0.0006 for both). As one of the secondary endpoints, the rate of change in the number of atrophic scars showed significant improvement from the baseline in the adapalene/benzoyl peroxide and benzoyl peroxide groups at week 24 (P = 0.0004 and P < 0.0001, respectively). Although the three‐dimensional image analysis parameters did not change significantly from the baseline in the adapalene/benzoyl peroxide and benzoyl peroxide groups at week 24, significant worsening was noted in the control group (P = 0.0276 for affected area, P = 0.0445 for volume, and P = 0.0182 for maximum depth). Adverse drug reactions were noted in three patients in the adapalene/benzoyl peroxide group (7.5%) but not in the benzoyl peroxide group. These findings suggest that maintenance therapy using adapalene 0.1%/benzoyl peroxide 2.5% gel and benzoyl peroxide 2.5% gel is effective in preventing the worsening of scars in Japanese patients with acne vulgaris.
Risk of bullous pemphigoid and pemphigus in patients on chronic dialysis: A nationwide population‐based cohort study
Authors: Tang Chao‐Hsiun , Sue Yuh‐Mou , Chang Chia‐Li , Wang Chia‐Chen
Published: September 2023

Bullous pemphigoid has a high incidence among dialysis patients. However, whether or not chronic dialysis is an independent risk factor of bullous pemphigoid remains unclear. We aimed to investigate the effect of chronic dialysis on the development of bullous pemphigoid and pemphigus. We performed a retrospective cohort study using records from Taiwan's National Health Insurance Research Database between 2008 and 2019. We identified a dialysis cohort that included patients on chronic hemodialysis and peritoneal dialysis, and the hazard ratios (HRs) for bullous pemphigoid and pemphigus were compared with those of a sex‐, age‐, and index‐matched cohort, then the results were adjusted for various confounding factors. Among 93 538 patients on chronic dialysis and 93 538 patients in the control group, 287 and 139 developed incident bullous pemphigoid, and 45 and 35 developed incident pemphigus after a median follow‐up of 3.7 and 5.6 years, respectively. The incidence rates of bullous pemphigoid in the dialysis patients and the control group were 74.2 and 25.2 per 100 000 person‐years, respectively (difference between groups, P < 0.0001). The incidence rates of pemphigus in the dialysis patients and the control group were 11.6 and 6.3 per 100 000 person‐years, respectively (difference between groups, P < 0.01). Cox proportional hazard adjustment showed the HR for bullous pemphigoid in dialysis patients was 2.12 (95% confidence interval [CI] 1.64–2.74, P < 0.0001) compared with the control group. Dialysis patients aged <75 years had an even higher risk of bullous pemphigoid development (5‐ to 8‐fold) than the control group. The adjusted HR for pemphigus was not elevated in dialysis patients (adjusted HR 1.52, 95% CI 0.87–2.67, P = 0.14). Chronic dialysis is an independent risk factor for developing bullous pemphigoid, but not a risk factor for pemphigus. Physicians should be aware of the predisposition of chronic dialysis patients to bullous pemphigoid.
Therapeutic effectiveness of upadacitinib on individual types of rash in Japanese patients with moderate‐to‐severe atopic dermatitis
Authors: Hagino Teppei , Yoshida Mai , Hamada Risa , Fujimoto Eita , Saeki Hidehisa , Kanda Naoko
Published: September 2023

Atopic dermatitis (AD) is a chronic eczematous disease with various types of rash, erythema, edema/papulation, excoriation, or lichenification. Janus kinase 1 inhibitor upadacitinib is effective for moderate‐to‐severe AD. We aimed to investigate the therapeutic effects of upadacitinib on each rash type in AD patients in real‐world clinical practice. Seventy‐two Japanese patients with moderate‐to‐severe AD were treated with oral upadacitinib 15 mg/day plus topical corticosteroids. The Eczema Area and Severity Index (EASI) scores for erythema, edema/papulation, excoriation, or lichenification on the whole body or on head and neck, upper limbs, lower limbs, or trunk were assessed at weeks 0, 4, and 12 of treatment. The proportions of patients who achieved resolution or at least 75% reduction of EASI from baseline (EASI 75) for individual rash types were calculated at weeks 4 and 12 on the whole body or each anatomical site. The resolution rates for excoriation, erythema, edema/papulation, or lichenification on the whole body were 38.3%, 23.7%, 21.7%, and 8.3% at week 4 and 18.3%, 18.6%, 11.6%, and 13.3% at week 12, respectively. The EASI scores for all rash types significantly decreased at weeks 4 and 12 compared to week 0. The achievement rates of EASI 75 for excoriation, erythema, edema/papulation, or lichenification on the whole body were 67.2%, 66.7%, 49.2%, and 37.7% at week 4 and 57.3%, 65%, 41%, and 41% at week 12, respectively. The achievement rate of EASI 75 for erythema on head and neck at week 4 (45.3%) was lower than that on upper limbs (71%) and on lower limbs (70.8%), and that on head and neck at week 12 (42.2%) was lower than that on lower limbs (69.2%). These results indicate that upadacitinib is effective for all AD rash types, especially for excoriation and erythema, while head‐and‐neck erythema might be less responsive to upadacitinib.
Skin manifestations and biophysical changes following weight reduction induced by bariatric surgery: A 2‐year prospective study
Authors: Triwatcharikorn Jidapa , Itthipanichpong Yada , Washrawirul Chanudda , Chuenboonngarm Nunthanach , Chongpison Yuda , Udomsawaengsup Suthep , Boonchaya‐Anant Patchaya , Rerknimitr Pawinee
Published: September 2023

Skin manifestations and biophysical changes are observed in patients with morbid obesity. However, reports of changes after significant weight loss, particularly through post‐bariatric surgery (BaS), are limited. The aim of this 2‐year prospective study was to evaluate the prevalence of skin signs and their changes in patients with morbid obesity who underwent BaS. Thirty‐one patients were recruited for the study, with a mean age of 38.35 (SD 10.61) years and a male preponderance (male = 19 [61.29%], female = 12 [38.71%]). Patients were scheduled for multiple visits at months 0, 3, 6, 12, 18, and 24 post‐BaS. Each subject had a thorough skin examination, biophysical measurements, and laboratory tests at each visit. Striae, acanthosis nigricans (AN), and plantar hyperkeratosis were the most common skin findings (n = 30 [96.77%], 29 [93.55%], 29 [93.55%], respectively). BaS provided improvements in many skin manifestations, namely striae, AN, acrochordons, plantar hyperkeratosis, hirsutism, lymphedema, pruritus, acne, finger pebbles, and chronic venous insufficiency with varied cumulative rates of improvements. However, acute telogen effluvium was observed in 17 (54.84%) patients. Regarding skin biophysical properties, transepidermal water loss, skin hydration, and pH did not change, while sebum production on the face significantly decreased at months 3 and 6, and elasticity decreased at months 6 and 24. In conclusion, weight reduction by BaS provided improvements in various skin signs, although telogen effluvium was a common sequelae.
Evaluating the determinants of load capacity factor in Japan: The impact of economic complexity and trade globalization
Authors: Awosusi Abraham Ayobamiji , Adebayo Tomiwa Sunday , Kirikkaleli Dervis , Rjoub Husam , Altuntaş Mehmet
Published: September 2023

Sustainable growth and the reduction of environmental pressures are important priorities that are issues of concern for both developed and developing countries. However, while carbon emissions and ecological footprint are commonly used by researchers in the context of environmental deterioration, a broader and more extensive metric for ecological quality is considered necessary. From this perspective, the load capacity factor provides a more detailed sustainable environment appraisal by simultaneously considering biocapacity and ecological footprint. Limited studies have examined the determinants of load capacity factor (LCAP). This survey attempts to fill the gap, using the case of Japan. Employing the dynamic ARDL approaches, the present research investigates the effect of renewable energy usage, economic growth, economic complexity, financial development, and trade globalization on load capacity factor in Japan for the period between 1980 and 2017. The empirical evidence indicates that economic complexity, economic growth, and financial development adversely impact LCAP, whereas renewable energy usage and trade globalization positively affect LCAP. Hence, we recommend that it is essential for Japan to attain self‐sufficiency in essential goods and minimize its reliance on the rest of the world. Furthermore, policymakers should capitalize on the benefits of trade globalization by adopting additional measures aimed at facilitating trade liberalization.