bluuebunny/crossref_metadata_2025 huggingface dataset:
p53 secures the normal behavior of H3.1 histone in the nucleus by regulating nuclear phosphatidic acid and EZH2 during the G1/S phase
Authors: Oikawa Tsukasa , Hasegawa Junya , Handa Haruka , Ohnishi Naomi , Onodera Yasuhito , Hashimoto Ari , Sasaki Junko , Sasaki Takehiko , Ueda Koji , Sabe Hisataka
Published: June 2023

Histones are key molecules of epigenetic regulation and inheritance, and are thought to be chaperoned and transported into the nucleus appropriately prior to being integrated into nucleosomes. H3.1 histone is predominantly synthesized and enters the nucleus during the G1/S phase of the cell cycle, as a new component of duplicating nucleosomes. Here we found that p53 is necessary to secure the normal behavior and modification of H3.1 in the nucleus during the G1/S phase, in which p53 increases C-terminal domain nuclear envelope phosphatase 1 (CTDNEP1) levels and decreases enhancer of zeste homolog 2 (EZH2) levels in the H3.1 interactome. In the absence of p53, H3.1 molecules tended to be tethered at or near the nuclear envelope (NE), where they were predominantly trimethylated at lysine 27 (H3K27me3) by EZH2, without forming nucleosomes. This accumulation was likely caused by the high affinity of H3.1 towards phosphatidic acid (PA). p53 reduced nuclear PA levels by increasing levels of CTDNEP1, which activates lipin to convert PA into diacylglycerol. Induction of theTMEM255Agene by p53 linked p53 with CTDNEP1, in which TMEM255A stabilized CTDNEP1. We moreover found that the cytosolic H3 chaperone HSC70 attenuates the H3.1-PA interaction, and our molecular imaging analyses suggested that H3.1 molecules may be anchored around the NE after their nuclear entry. Our results expand our knowledge of p53 function in regulation of the nuclear behavior of H3.1 during the G1/S phase, in which p53 may primarily target nuclear PA and EZH2.
Paridiprubart inhibits TLR4-dependant NF-κB activation by multiple pathogens
Authors: Malty Ramy , Hilbe Richard , Ahn Sang , Kesselman Leah , Lam Jessica , Kasawara Karina , Costa Larissa , Rajakulendran Nishani , Gordon Blair , Brooks Michael , Mubareka Samira , Tancevski Ivan , Gray-Owen Scott D.
Published: June 2023

Respiratory pathogens such as SARS-CoV-2 and influenza can activate an exaggerated inflammatory response (cytokine storm) in the lungs that may result in acute respiratory distress syndrome (ARDS), hospitalization, and death. Therapies that target a specific pathogen (i.e. anti-virals) must, by nature, be selected after a specific diagnosis and may become ineffective due to pathogen evolution. An alternate strategy is to counter the exaggerated innate immune response present in ARDS patients using host-directed drug therapies that are agnostic to the infectious agent to overcome both of these challenges. Originally described as the innate immune receptor for lipopolysaccharide (LPS), Toll-like receptor 4 (TLR4) is now understood to be an important mediator of inflammation caused by a variety of pathogen-associated molecular patterns (PAMPs) and host-derived damage-associated molecular patterns (DAMPs). Here we show that paridiprubart, a monoclonal antibody that prevents TLR4 dimer formation, inhibits the response to TLR4 agonists including LPS, the SARS-CoV-2 spike protein, the DAMP high mobility group box 1 (HMGB1), as well as the NF-κB response to infection by both viral and bacterial pathogens. Notable in this regard, we demonstrate that SARS-CoV-2 increases HMGB1 levels, and that paridiprubart inhibits both the SARS-CoV-2 and HMGB1-triggered NF-κB response, illustrating its potential to suppress this self-amplifying inflammatory signal. We also observed that the inhibitory effect of paridiprubart is apparent when cells are exposed to the SARS-CoV-2 spike protein, which is itself a direct TLR4 agonist. In the context of active infection, paridiprubart suppressed the NF-κB-dependent response elicited by infection with SARS-CoV-2, the seasonal coronavirus 229E, influenza A virus orHaemophilus influenzae, a gram-negative bacterial pathogen. Combined, these findings reinforce the central role played by TLR4 in the inflammatory response to infection by diverse pathogens, and demonstrates the protective potential of paridiprubart-dependent inhibition of pathogenic TLR4 responses.
50-nm gas-filled protein nanostructures to enable the access of lymphatic cells by ultrasound technologies
Authors: Shen Qionghua , Li Zongru , Meyer Matthew D. , De Guzman Marc T. , Lim Janie C. , Bouchard Richard R. , Lu George J.
Published: June 2023

Ultrasound imaging and ultrasound-mediated gene and drug delivery are rapidly advancing diagnostic and therapeutic methods; however, their use is often limited by the need of microbubbles, which cannot transverse many biological barriers due to their large size. Here we introduce 50-nm gas-filled protein nanostructures derived from genetically engineered gas vesicles that we referred to as50nmGVs. These diamond-shaped nanostructures have hydrodynamic diameters smaller than commercially available 50-nm gold nanoparticles and are, to our knowledge, the smallest stable, free-floating bubbles made to date.50nmGVs can be produced in bacteria, purified through centrifugation, and remain stable for months. Interstitially injected50nmGVs can extravasate into lymphatic tissues and gain access to critical immune cell populations, and electron microscopy images of lymph node tissues reveal their subcellular location in antigen-presenting cells adjacent to lymphocytes. We anticipate that50nmGVs can substantially broaden the range of cells accessible to current ultrasound technologies and may generate applications beyond biomedicine as ultrasmall stable gas-filled nanomaterials.
Nuclear quality control of non-imported secretory proteins attenuates proteostasis decline in the cytosol
Authors: Banik Papiya , Kamps Janine , Chen Qi-Yin , Luesch Hendrik , Winklhofer Konstanze F. , Tatzelt Jörg
Published: June 2023

Mistargeting of secretory proteins to the cytosol can induce formation of aggregation-prone conformers and subsequent proteostasis decline. We have identified a quality control pathway that redirects non-ER-imported prion protein (PrP) to proteasomal degradation in the nucleus to prevent formation of toxic aggregates in the cytosol. Upon aborted ER import, PrP sequentially interacted with VCP/p97 and importins, which kept PrP soluble and promoted its nuclear import. In the nucleus, RNA buffered aggregation of PrP to facilitate ubiquitin-dependent proteasomal degradation. Notably, the cytosolic interaction of PrP with VCP/p97 and its nuclear import were independent of ubiquitination but required the intrinsically unstructured N-terminal domain of PrP. Transient proteotoxic stress promoted the formation of self-perpetuating PrP aggregates in the cytosol, which disrupted further nuclear targeting of PrP and compromised cellular proteostasis. Our study delineates a VCP/p97-dependent nucleus-based quality control pathway of non-ER-imported secretory proteins and emphasizes the important role of the nuclear milieu for the degradation of aggregation-prone proteins.
Deep learning pipeline reveals key moments in human embryonic development predictive of live birth in IVF
Authors: Mapstone Camilla , Hunter Helen , Brison Daniel , Handl Julia , Plusa Berenika
Published: June 2023

Demand for IVF treatment is growing, however success rates remain low partly due to difficulty in selecting the best embryo to be transferred. Current manual assessments are subjective and may not take advantage of the most informative moments in embryo development. Here, we apply convolutional neural networks (CNNs) to identify key windows in preimplantation human development that can be linked to embryo viability and are therefore suitable for the early grading of IVF embryos. We show how machine learning models trained at these developmental time-points can be used to refine overall embryo viability assessment. Exploiting the well-known capabilities of transfer learning, we illustrate the performance of CNN models for very limited data sets, paving the way for the use on a clinic-by-clinic basis, catering for local data heterogeneity.
DENetwork: Unveiling Regulatory and Signaling Networks Behind Differentially-Expressed Genes
Authors: Su Ting-Yi , Islam Quazi S. , Huang Steven K. , Baglole Carolyn J. , Ding Jun
Published: June 2023

Differential gene expression analysis from RNA-sequencing (RNA-seq) data offers crucial insights into biological differences between sample groups. However, the conventional focus on differentially-expressed (DE) genes often omits non-DE regulators, which are an integral part of such differences. Moreover, DE genes frequently serve as passive indicators of transcriptomic variations rather than active influencers, limiting their utility as intervention targets. To address these shortcomings, we have developedDENetwork. This innovative approach deciphers the intricate regulatory and signaling networks driving transcriptomic variations between conditions with distinct phenotypes. Unique in its integration of both DE and critical non-DE genes in a graphical model,DENetworkenhances the capabilities of traditional differential gene analysis tools, such asDESeq2. Our application ofDENetworkto an array of simulated and real datasets showcases its potential to encapsulate biological differences, as demonstrated by the relevance and statistical significance of enriched gene functional terms.DENetworkoffers a robust platform for systematically characterizing the biological mechanisms that underpin phenotypic differences, thereby augmenting our understanding of biological variations and facilitating the formulation of effective intervention strategies.
Divergent hepaciviruses, chuvirus and deltaviruses in Australian marsupial carnivores (Dasyurids) identified through transcriptome mining
Authors: Harvey Erin , Mifsud Jonathon C.O. , Holmes Edward C. , Mahar Jackie E.
Published: June 2023

Although Australian marsupials are characterised by unique biology and geographic isolation, little is known about the viruses present in these iconic wildlife species. The Dasyuromorphia are an order of marsupial carnivores found only in Australia that include both the extinct Tasmanian tiger (Thylacine) and the highly threatened Tasmanian devil. Several other members of the order are similarly under threat of extinction due to habitat loss, hunting, disease, and competition and predation by introduced species such as feral cats. We utilised publicly available RNA-seq data from the NCBI Sequence Read Archive (SRA) database to document the viral diversity within four Dasyuromorphia species. Accordingly, we identified 15 novel virus species from five DNA virus families (Adenoviridae,Anelloviridae,Herpesviridae,PapillomaviridaeandPolyomaviridae) and three RNA virus taxa: the orderJingchuvirales,the genusHepacivirus, and the delta-like virus group. Of particular note was the identification of a marsupial specific clade of delta-like viruses that may indicate an association of deltaviruses and with marsupial species dating back to their origin some 160 million years ago. In addition, we identified a highly divergent hepacivirus in a numbat liver transcriptome that falls outside of the larger mammalian clade, as well as the first detection of theJingchuviralesin a mammalian host – a chu-like virus in Tasmanian devils – thereby expanding the host range beyond invertebrates and ectothermic vertebrates. As many of these Dasyuromorphia species are currently being used in translocation efforts to reseed populations across Australia, understanding their virome is of key importance to prevent the spread of viruses to naive populations.
Multifaceted effects oneven-skippedtranscriptional dynamics uponKrüppeldosage changes
Authors: Lin Shufan , Lim Bomyi
Published: June 2023

Although fluctuations in transcription factor (TF) dosage are often well tolerated, little is known about how TF dosage modulation changes the target gene expression dynamics and results in subsequent developmental phenotypes. Using MS2/MCP-mediated quantitative live imaging in earlyDrosophilaembryos, we characterized transcriptional dynamics of the pair-rule geneeven-skipped(eve) upon changing the gap geneKrüppel(Kr) level. DecreasingKrdosage by half leads to a transient posterior expansion of theevestripe 2 and an anterior shift of stripe 5. Surprisingly, the most significant changes are observed inevestripes 3 and 4, whose enhancers do not contain Kr binding sites. For both stripes, the widths of stripes are narrowed, boundaries are located more anteriorly, and the mRNA production level is reduced inKrheterozygous embryos. We show that Kr dosage indirectly affects stripes 3 and 4 dynamics by modulating other gap gene dynamics. We quantitatively correlate moderate body segment phenotypes ofKrheterozygotes with spatiotemporal changes ineveexpression. Our results indicate that nonlinear relationships between TF dosage and phenotypes underlie direct TF-DNA and indirect TF-TF interactions.

Summary statement

This study analyzed the changes in transcriptional dynamics ofeven-skippedupon halvingKrüppeldosage, and revealed how the combination of direct TF-DNA and indirect TF-TF interactions shape proper patterning.
Identification of small molecule inhibitors of G3BP-driven stress granule formation
Authors: Freibaum Brian D. , Messing James , Nakamura Haruko , Yurtsever Ugur , Wu Jinjun , Kim Hong Joo , Hixon Jeff , Lemieux Rene , Duffner Jay , Huynh Walter , Wong Kathy , White Michael , Lee Christia , Meyers Rachel , Parker Roy , Taylor J. Paul
Published: June 2023

Stress granule formation is triggered by the release of mRNAs from polysomes and is promoted by the action of the paralogs G3BP1 and G3BP2. G3BP1/2 proteins bind mRNAs and thereby promote the condensation of mRNPs into stress granules. Stress granules have been implicated in several disease states, including cancer and neurodegeneration. Consequently, compounds that limit stress granule formation or promote their dissolution have potential as both experimental tools and novel therapeutics. Herein, we describe two small molecules, referred to as G3BP inhibitor a and b (G3Ia and G3Ib), designed to bind to a specific pocket in G3BP1/2 that is known to be targeted by viral inhibitors of G3BP1/2 function. In addition to disrupting co-condensation of RNA, G3BP1, and caprin 1in vitro, these compounds inhibit stress granule formation in cells treated prior to or concurrent with stress, and dissolve pre-existing stress granules when added to cells after stress granule formation. These effects are consistent across multiple cell types and a variety of initiating stressors. Thus, these compounds represent ideal tools to probe the biology of stress granules and hold promise for therapeutic interventions designed to modulate stress granule formation.
Lysine vitcylation is a novel vitamin C-derived protein modification that enhances STAT1-mediated immune response
Authors: He Xiadi , Wei Yun , Wu Jiang , Wang Qiwei , Bergholz Johann S. , Gu Hao , Zou Junjie , Lin Sheng , Wang Weihua , Xie Shaozhen , Jiang Tao , Lee James , Asara John M. , Zhang Ke , Cantley Lewis C. , Zhao Jean J.
Published: June 2023

Vitamin C (vitC) is a vital nutrient for health and also used as a therapeutic agent in diseases such as cancer. However, the mechanisms underlying vitC’s effects remain elusive. Here we report that vitC directly modifies lysine without enzymes to form vitcyl-lysine, termed “vitcylation”, in a dose-, pH-, and sequence-dependent manner across diverse proteins in cells. We further discover that vitC vitcylates K298 site of STAT1, which impairs its interaction with the phosphatase PTPN2, preventing STAT1 Y701 dephosphorylation and leading to increased STAT1-mediated IFN pathway activation in tumor cells. As a result, these cells have increased MHC/HLA class-I expression and activate immune cells in co-cultures. Tumors collected from vitC-treated tumor-bearing mice have enhanced vitcylation, STAT1 phosphorylation and antigen presentation. The identification of vitcylation as a novel PTM and the characterization of its effect in tumor cells opens a new avenue for understanding vitC in cellular processes, disease mechanisms, and therapeutics.
The Role of VSL#3® in the Treatment of Fatigue and Other Symptoms in Long Covid-19 Syndrome: a Randomized, Double-blind, Placebo-controlled Pilot Study (DELong#3)
Authors: Marinoni Beatrice , Rimondi Alessandro , Bottaro Federico , Ciafardini Clorinda , Amoroso Chiara , Muià Martina , Caridi Bruna , Noviello Daniele , Bandera Alessandra , Gori Andrea , Mantero Marco , Blasi Francesco , Ferrucci Roberta , Facciotti Federica , Vecchi Maurizio , Caprioli Flavio
Published: June 2023

Long COVID, also known as Post-acute COVID-19 Syndrome (PACS), is a chronic condition affecting individuals who have recovered from acute COVID-19. It is currently estimated that around 65 million people worldwide suffer from Long COVID. It is characterized by a range of symptoms, including fatigue, exertion intolerance, neurocognitive and sensory impairment, sleep disturbance, myalgia/arthralgia, and dysautonomia. Among them fatigue has emerged as a burdensome and pervasive issue, significantly impacting the quality of life and daily functioning of Long COVID patients. Alterations in the composition of the intestinal microbiota has been reported in COVID-19 patients. Dysbiosis persists even after several months of recovery from acute SARS-CoV-2 infection.

Based on this evidence, we carried out a phase 3, randomized, double-blind, placebo-controlled trial aimed at evaluating the efficacy of VSL#3®, a consortium of probiotic bacterial strains, in reducing fatigue and improving various aspects of patients’ well-being in patients with Long COVID syndrome.

Highlights

Patients suffering from Long-COVID manifest a variety of persistent symptoms impacting daily functioning;

Fatigue emerged as a burdensome and pervasive issue, significantly impacting the quality of life;

VSL#3® treatment significantly reduced the Chalder Fatigue Scale scores as compared to placebo

Chalder Fatigue Scale scores remained significantly reduced in the treatment group 4 weeks post intervention.
Evidence for increased stress resistance due to polyploidy from synthetic autotetraploidCaenorhabditis elegans
Authors: Chauve Laetitia , Bazzani Emma , Verdier Clément , Butler Liam , Atimise Martha E. , McGarry Aoibhín , McLysaght Aoife
Published: June 2023

Whole genome duplication (WGD) is a well-studied yet enigmatic phenomenon. While it has long been recognised as contributing numerous genes to many eukaryotic lineages and often implicated in evolutionary radiations, how these lineages overcome the known burdens of polyploidy is poorly understood. Circumstantial evidence of many WGD events coinciding with periods of otherwise mass extinction is consistent with the hypothesis that polyploidy is conditionally advantageous under stress conditions. While support for this comes from both theoretical work and field studies, direct evidence is lacking, especially in animals. Here we compare diploid and neo-tetraploidCaenorhabditis elegansand show that tetraploid animals exhibit increased resilience under specific stress conditions related to temperature changes. Most notably, under severe cold stress gravid neo-tetraploids massively escape cold-induced death, and generate more progeny, of similar quality, than diploid animals. This is the first demonstration of the effects of polyploidy on stress resistance and physiology in animals.
Nuclear lamin A/C phosphorylation by loss of Androgen Receptor is a global determinant of cancer-associated fibroblast activation
Authors: Ghosh Soumitra , Isma Jovan , Mazzeo Luigi , Toniolo Annagiada , Simon Christian , Dotto G. Paolo
Published: June 2023

Alterations of nuclear structure and function, and associated impact on gene transcription, are a hallmark of cancer cells. Little is known of these alterations in Cancer-Associated Fibroblasts (CAFs), a key component of the tumor stroma. Here we show that loss of androgen receptor (AR), which triggers early steps of CAF activation in human dermal fibroblasts (HDFs), leads to nuclear membrane alterations and increased micronuclei formation, which are unlinked from induction of cellular senescence. Similar alterations occur in fully established CAFs, which are overcome by restored AR function. AR associates with nuclear lamin A/C and loss of AR results in a substantially increased lamin A/C nucleoplasmic redistribution. Mechanistically, AR functions as a bridge between lamin A/C with the protein phosphatase PPP1. In parallel with a decreased lamin-PPP1 association, AR loss results in a marked increase of lamin A/C phosphorylation at Ser 301, which is also a feature of CAFs. Phosphorylated lamin A/C at Ser 301 binds to the transcription promoter regulatory region of several CAF effector genes, which are upregulated due to the loss of AR. More directly, expression of a lamin A/C Ser301 phosphomimetic mutant alone is sufficient to convert normal fibroblasts into tumor-promoting CAFs of the myofibroblast subtype, without an impact on senescence. These findings highlight the pivotal role of the AR-lamin A/C-PPP1 axis and lamin A/C phosphorylation at Ser 301 in driving CAF activation.
Is “regional culture” a meaningful concept? Cultural differences across 60 Russian regions
Authors: Minkov Michael , Sokolov Boris , Ponarin Eduard , Almakaeva Anna , Nastina Ekaterina
Published: June 2023

Purpose

There is an increasing interest in the international management literature in cultural differences between in-country regions. Yet, the regions of any country may be merely political products and not necessarily cultural units. The goal of this article is to propose clear empirical criteria for deciding if a set of entities, such as a country's administrative regions, can be legitimate units of cross-cultural analysis and to test these criteria in an empirical study.

Design/methodology/approach

The authors review the literature on what constitutes a unit of cross-cultural analysis and propose empirical criteria. For instance, the regions of a given country are meaningful units of cross-cultural analysis if one can replicate (an) established dimension(s) of culture at the regional level, including some of the dimension(s)' antecedents and predictive properties. The authors apply this test in the context of the Russian Federation (RF), using an RF database (18,768 respondents from 60 administrative regions) with items borrowed from the World Values Survey.

Findings

The RF regions pass the authors’ test. At the regional level, the selected items yield an individualism-collectivism (IDV-COLL) dimension that is similar to its nation-level counterpart in the revised Minkov-Hofstede model in terms of concept and antecedents (wealth differences and geographic latitude) and outcomes that are relevant in business (innovation rates and quality of governance). The authors also find other patterns that confirm the properties of RF regions as meaningful units of cultural analysis.

Research limitations/implications

The authors’ criteria and the test based on them are suitable for large countries, with significant geo-climatic variety and ethnic diversity, but may be inapplicable in small countries with less diversity. It is questionable if the latter countries contain enough cultural variation to justify a cross-cultural analysis of their sub-national regions.

Practical implications

The authors’ criteria can be used in future research in any large country to decide if its regions justify a cross-cultural analysis in the field of management and business or any other field.

Social implications

Cultural differences within a country are important as they may inform political and management decisions. Yet, to demonstrate that those differences are real, and not imaginary, one needs a methodology like the authors’.

Originality/value

The study contributes to the discussion of the meaningfulness of in-country regions as cultural units for cross-cultural analysis in international business by focusing on the RF.
Past, present and future of augmented reality marketing research: a bibliometric and thematic analysis approach
Authors: Jayaswal Pragya , Parida Biswajita
Published: June 2023

Purpose

Augmented reality (AR) has emerged as a new interactive technology, swiftly transforming the field of marketing. Driven by its rapid uptake in marketing practices, academic research on AR has proliferated. This study aims to offer a holistic view of the past, present and future of augmented reality marketing (ARM) scholarship by analyzing its current and evolving research profile as well as its social and conceptual structures to inspire further research.

Design/methodology/approach

This study enriches the ARM scholarship by integrating a quantitative bibliometric analysis with a chronological-thematic review and a qualitative content analysis to develop a more comprehensive understanding of this novel area and suggest future research courses.

Findings

The bibliometric analysis reveals the key performance indicators as well as the social and conceptual structure of the ARM research field. The chronological-thematic review exhibits the advancement of ARM research over time and forecasts the emerging trends for the domain. Finally, the content analysis of recent articles reveals the current research hotspots and provides future research directions.

Research limitations/implications

The database limits the selection of literature, as the information in databases such as Scopus is updated regularly, resulting in alterations in the number of articles and citations.

Practical implications

AR developers and brand managers may use this study’s findings to understand the current ARM landscape better and make strategic decisions based on AR adoption and consumption patterns.

Originality/value

This study is singular in using a mixed methods approach by integrating the findings from bibliometric and content analyses for more reliable results and to offer a holistic perspective of the ARM sector, thereby significantly advancing the field of technology-led marketing.
Agency in entrepreneurship: preparing entrepreneurship theory for another view of context
Authors: Melin Erik , Gaddefors Johan
Published: June 2023

Purpose

The purpose of this article is to explore how agency is distributed between human actors and nonhuman elements in entrepreneurship.

Design/methodology/approach

It is based on an inductive longitudinal case study of a garden in a rural community in northern Sweden. The methodology includes an ethnography of the garden, spanning the course of 16 years, and a careful investigation of the entrepreneurial processes contained within it.

Findings

This article identifies and describes different practices to explain how agency is distributed between human actors and nonhuman elements in the garden's context. Three different practices were identified and discussed, namely “calling”, “resisting”, and “provoking”.

Originality/value

Agency/structure constitutes a longstanding conundrum in entrepreneurship and context. This study contributes to the on-going debate on context in entrepreneurship, and introduces a posthumanist perspective—particularly that of distributed agency—to theorising in entrepreneurship. Rather than focussing on a human (hero)-driven change process, induced through the exploitation of material objects, this novel perspective views entrepreneurship as both a human and a nonhuman venture, occurring through interactions located in particular places and times. Coming from the agency/structure dichotomy, this article reaches out for elements traditionally established on the structure side, distributing them to the agency side of the dichotomy. As such, it contributes to an understanding of the agency of nonhuman elements, and how they direct entrepreneurship in context. This theoretical development prepares entrepreneurship theories to be better able to engage with nonhuman elements and provides example solutions for the ongoing climate crisis.
Healthcare brands sound off: evaluating the influence of sonic branding in shaping consumer perceptions
Authors: Kemp Elyria , Kopp Steven W. , Bui My (Myla)
Published: June 2023

Purpose

Brand management has traditionally enlisted visual branding elements, including the brand’s graphic logo, to distinguish and communicate the personality of the brand. However, as healthcare organizations work to shape how consumers perceive their brand, organizations are also enhancing their brand identity with sound and music by creating a sonic brand. This research paper aims to examine how sonic brands influence consumer emotional reactions and trust in a healthcare provider. It also explores how sonic brands can differentially affect consumers, depending on their level of engagement in their physical and mental health.

Design/methodology/approach

Two experimental studies were conducted that tested the use of a sonic logo for healthcare providers in consumption contexts that might elicit negative emotions, cancer care and mental health care.

Findings

The results suggest that the presence of a sonic logo helped to alleviate negative emotions as well as engender trust in the provider. Findings also revealed that for consumers who are less engaged in their health, a sonic logo served as a peripheral cue by enhancing perceptions of competence and empathy for the healthcare provider.

Originality/value

Findings from this research provide insight into how sonic brands can increase the effectiveness of branded healthcare communications.
Female directors' representation and intellectual capital efficiency: does institutional ownership matter?
Authors: Mardini Ghassan H. , Elleuch Lahyani Fathia
Published: June 2023

Purpose

This study examines the impact of female directors' representation in the boardroom and the role of institutional ownership (IO) on intellectual capital efficiency (ICE) and its three efficiency components: human capital efficiency (HCE); innovation capital efficiency (INCE) and capital employed efficiency (CEE).

Design/methodology/approach

A sample of non-financial French firms listed within the Société des Bourses Françaises-120 (SBF-120) was employed for the period from 2011 to 2020 using the generalized method of moments (GMM) approach to test the set of hypotheses.

Findings

Grounded in agency and resource dependence theories, this study found that female directors play a vital role in enhancing ICE. IO also has a significant role to play. Active institutional investors tend to push toward gender-balanced boardrooms and play an external supervisory role to improve efficiency. Moreover, female financial experts on audit committees also contribute to the ICE decision-making process within firms with high IO levels.

Research limitations/implications

This study focused only on IO. Future research may use other forms of ownership, such as foreign or family ownership.

Practical implications

The findings may serve as a reference for managers and policymakers to enhance IC management and make appropriate investment decisions. Managers and policymakers may rely on strategic and effective decisions regarding the efficient use of IC for value creation through the judgments of female directors.

Originality/value

The current study adds significant insights to the accounting and intellectual capital literature.
Determinants and impacts of contract farming: evidence from cultivation of onion, okra and pomegranate in Maharashtra, India
Authors: Kumar Anjani , Roy Devesh , Tripathi Gaurav , Joshi P.K.
Published: June 2023

Purpose

This study investigates the impact of contract farming in onion, okra and pomegranate production on profits of smallholder farmers in India. It also investigates the determinants of farmers’ participation in contract farming. The study is based on a survey of 1,131 farmers from Maharashtra, India engaged in the cultivation of these three crops.

Design/methodology/approach

This study uses instrumental variable regressions and quasi-experimental methods to decipher the impact of contract farming.

Findings

The study reveals that contract farming ensures higher returns for smallholders, enables their access to high-end markets and brings in risk-sharing with protection during price fluctuations. Farm size and farmers’ risk perceptions are significantly associated with their participation in contract farming.

Research limitations/implications

The study is based on cross-sectional data, which presents limitations on considering unobserved farmer-level individual heterogeneity.

Originality/value

The study shows that contracts highlight the functioning of the contractor/integrator on both the input and output sides of the market. By providing better-quality inputs on credit and at discounted prices and by providing training, the integrator helps small farmers meet international food safety and quality standards, a historically difficult challenge for smallholders in India.
The pedagogy mix: teaching marketing effectively in business/management education
Authors: Maheshkar Chandan , Sonwalkar Jayant
Published: June 2023

Purpose

This paper aims to explore the key factors through which an optimum pedagogy mix can be determined towards effective teaching practice and enhanced student learning outcomes in business/management education.

Design/methodology/approach

An exploratory research design has been used. A sample of 310 was analyzed using exploratory factor analysis. A structured questionnaire was developed to collect data. It was pre-tested, and essential modifications were made before its final implementation.

Findings

The study has presented the idea of pedagogy mix, which refers to a set of most obvious teaching methods/tools suitable to deliver marketing education in a context-bound manner. Eight factors have been identified that help to decide and/or maintain an optimum mix of pedagogies for effective teaching. An adequate “pedagogy mix” would help achieve educational objectives and equip students with the essential competencies.

Practical implications

The study is particularly significant to educators who are in the initial years of their careers. The identified factors help educators decide and/or maintain an optimum mix of pedagogies by offering an understanding of different pedagogies, their strategic relevance and student needs.

Originality/value

An institution's academic philosophy and commitment to the learning outcomes make it excellent or poor. Present institutions have and retain a main focus on preparation for professional careers, and without a perfect blend of pedagogies, it cannot be achieved. An optimum pedagogy mix would facilitate the key learning process and proffer the intricacies of the concerned profession. In this sense, this paper is a significant attempt, particularly in management education and higher education in general, that enables the educators of higher academics to decide and utilize an idyllic blend of pedagogies towards the successful execution of an educational process of higher order and ensuring the holistic student development.
Effects of Internet of Things, supply chain collaboration and ethical sensitivity on sustainable performance: moderating effect of supply chain dynamism
Authors: Billah Mohammed Masum , Alam Syed Shah , Masukujjaman Mohammad , Ali Mohd Helmi , Makhbul Zafir Khan Mohamed , Salleh Mohd Fairuz Md
Published: June 2023

Purpose

The survival and growth of the ready-made garments (RMGs) sectors in Bangladesh depend on sustainable supply chain performance (SSCP). The purpose of this study is to analyse the effects of Internet of Things (IoT), supply chain collaboration and ethical sensitivity on SSCP. Also, supply chain dynamism was tested as a moderator.

Design/methodology/approach

The framework of this study has been developed to enrich the understanding of technology usage in the supply chain. In developing the framework, previous studies in the supply chain context were considered. The model was tested by using data collected from 290 executives that were employed by different RMG companies in Bangladesh. This study used a 29-item structured questionnaire measured on a 6-point Likert scale to collect the data. Covariance-based structural equation modelling (SEM) was utilised to test the data.

Findings

The results showed that there were statistically significant and positive relationships between IoT and supply chain collaboration, social performance, economic performance and environmental performance. Ethical sensitivity also influenced social and economic performance. Supply chain collaboration was found to be related to social, economic and environmental performance. However, no link was found between ethical sensitivity and environmental performance. The result also showed that supply chain dynamism acted as a moderator.

Research limitations/implications

By considering theories and interpreting the results, this study provides some theoretical and practical implications which will enhance the SSCP. The results can also facilitate strategic planning by companies.

Originality/value

This research has identified and analysed the effect of IoT on SSCP in the RMGs industry in Bangladesh where this industry serves as the main economic contributor.
CEO attributes and foreign shareholdings: evidence from an emerging economy
Authors: Chakraborty Dipanwita , Mahakud Jitendra
Published: June 2023

Purpose

This paper aims to examine the impact of chief executive officer (CEO) attributes on foreign shareholdings from the perspective of an emerging economy.

Design/methodology/approach

This study examined Bombay Stock Exchange listed firms from the Indian stock market and applied a balanced panel data approach with fixed effect estimation technique during the period 2010–2019.

Findings

The study shows that CEOs’ financial education and a higher level of education positively affect foreign shareholdings. The age and experience of CEO have a positive and significant impact on foreign shareholdings. Firms with male CEOs are preferred more by foreign investors. The effect of CEO busyness and CEO duality is negative on foreign shareholdings. Foreign investors prefer to invest in firms with foreign nationality CEOs. Furthermore, the robustness test reveals that the influence of CEO attributes on foreign shareholdings is stronger for new, small and stand-alone firms than for old, large and group-affiliated firms.

Practical implications

The study will be beneficial for a diverse audience ranging from firms’ board of directors, regulators and policymakers who are entrusted with the CEO recruitment process. Additionally, firms seeking external financing should disclose CEO information adequately and improve the reporting quality to attract foreign investors, as they consider CEO characteristics as a valuable signal before making investment decisions.

Originality/value

In light of the current legislative reforms, this study can be recognized as one of the early studies that explore the relationship between CEO attributes and foreign shareholdings in the context of an emerging economy.
“Revealing the hidden” – challenges facing early digital entrepreneurs in Jordan
Authors: Abaddi Samer , AL-Shboul Moh'd Anwer
Published: June 2023

Purpose

Digital entrepreneurship is the key to economic survival and the lantern of jobs in developing countries. The debate about the challenges facing early digital entrepreneurs (DEs) in developing countries is still ambiguous. This study attempts to fulfill the gap with an in-depth examination of Jordan.

Design/methodology/approach

Referring to a digital start-up database hosted by the Ministry of Digital Economy and Entrepreneurship in Jordan, the study interviews a random sample of (n = 45) early (less than one-year seniority) DEs. Thematic analysis is carried out facilitated by NVivo 20 software. E-Commerce, agriculture technology, data and artificial intelligence and entertainment were at the top of the interviewed start-ups.

Findings

Nine challenges were observed, critically analyzed and discussed. The challenges are (1) the lack of realistic funding in terms and guarantees; (2) the negligence of guidance and advisory of incubators and entrepreneurship centres; (3) the emergence of unexpected risks; (4) the stringent economic situation; (5) competition; (6) legal and legislative obstacles; (7) obstacles to accessing markets; (8) team management and finally (9) disorganization in the entrepreneurial environment. The study sets recommendations to support early DEs in their journey.

Practical implications

This study highlights the significant implications for aspiring DEs by focusing on some challenges that might face their start-ups such as institutional, technology and local dimensions of context and measures to develop the entrepreneurial and digital competencies. This includes sustainable funding, poor direct guidance and advisory, unexpected failures/risks, and economic obstacles. This study might be considered a road map for the decision-makers to build their strategies for eliminating the main barriers for early DEs and start-ups.

Originality/value

Although recent literature discussed the challenges of entrepreneurs in Jordan, this is the first that identifies early DEs’ challenges and uses 45% samples of the community.
Synergy between rural and smart tourism: is it possible and necessary?
Authors: Auzina Anita , Zvirbule Andra , Jankova Liga
Published: June 2023

Purpose

The study aims to identify the opinions of rural tourism service providers on synergy between rural and smart tourism in Latvia, Zemgale region.

Design/methodology/approach

The research is of a qualitative nature and it profiles possibilities for and the necessity of synergy between rural and smart tourism. As part of the study, a survey was conducted to identify the opinions of 63 rural tourism service providers from the Zemgale region.

Findings

The study found that rural tourism service providers use digital tools mainly for payment, communication with customers as well as marketing activities, which revealed that the level of digitalization of rural tourism in Latvia is low. The survey data indicates the respondents' dual vision of synergy between rural and smart tourism, recognizing that IT progress was rapid and its influence was inevitable, while at the same time emphasizing an argument for maintaining the basic value and nature of rural tourism.

Originality/value

The paper is an original study of the opinions of rural tourism service providers on synergy between rural and smart tourism in Latvia and specifically, the Zemgale region.
Reasonableness in Capacity Law
Authors: Hass Binesh
Published: June 2023

It is not uncommon for people to hold bizarre views. Sometimes, these views appear before the courts in mental capacity cases. Judges must then decide if the views are so bizarre that they constitute evidence of incapacity or, instead, if those views are the everyday sort that do not constitute such evidence. The idea behind the distinction is that the everyday sort can be false but, in some important sense, not that unreasonable. But what should tip the balance of reasons for a view to count as severely unreasonable rather than merely so? It turns out that capacity law is unable to provide a principled answer to this question because it lacks a standard to parse beliefs. This paper offers such a standard, focussing on the ability to reason, or the ‘use and weigh’ criterion, which features in most capacity statutes. The standard takes the form of a threshold with four necessary conditions. The main idea is that when a person's belief satisfies those conditions, it counts as evidence of an inability to reason. The standard's objective is to displace the various unarticulated conceptions of reasonableness which judges are currently compelled to use to determine questions of reasoning ability.
Role of climatic variability in shaping intraspecific variation of thermal tolerance in Mediterranean water beetles
Authors: Pallarés Susana , Garoffolo David , Rodríguez Belén , Sánchez‐Fernández David
Published: June 2023

The climatic variability hypothesis (CVH) predicts that organisms in more thermally variable environments have wider thermal breadths and higher thermal plasticity than those from more stable environments. However, due to evolutionary trade‐offs, taxa with greater absolute thermal limits may have little plasticity of such limits (trade‐off hypothesis). The CVH assumes that climatic variability is the ultimate driver of thermal tolerance variation across latitudinal and altitudinal gradients, but average temperature also varies along such gradients. We explored intraspecific variation of thermal tolerance in three typical Mediterranean saline water beetles (families Hydrophilidae and Dytiscidae). For each species, we compared two populations where the species coexist, with similar annual mean temperature but contrasting thermal variability (continental vs. coastal population). We estimated thermal limits of adults from each population, previously acclimated at 17, 20, or 25 °C. We found species‐specific patterns but overall, our results agree with the CVH regarding thermal ranges, which were wider in the continental (more variable) population. In the two hydrophilid species, this came at the cost of losing plasticity of the upper thermal limit in this population, supporting the trade‐off hypothesis, but not in the dytiscid one. Our results support the role of local adaptation to thermal variability and trade‐offs between basal tolerance and physiological plasticity in shaping thermal tolerance in aquatic ectotherms, but also suggest that intraspecific variation of thermal tolerance does not fit a general pattern among aquatic insects. Overlooking such intraspecific variation could lead to inaccurate predictions of the vulnerability of aquatic insects to global warming.
Tofacitinib versus methotrexate as the first‐line disease‐modifying antirheumatic drugs in the treatment of rheumatoid arthritis: An open‐label randomized controlled trial
Authors: Khan Mohammad Mamun , Ahmed Shamim , Hasan Sajib Md Kamrul , Morshed Abdullah All , Mahbub‐Uz‐Zaman Khandker , Haq Syed Atiqul
Published: June 2023

Objective

To compare tofacitinib and methotrexate (MTX) as first‐line disease‐modifying antirheumatic drugs (DMARDs) for rheumatoid arthritis (RA).

Methods

This open‐label, randomized controlled, parallel‐group, 3‐month trial randomly assigned 100 RA patients to tofacitinib 10 mg daily (49 patients) or MTX 25 mg subcutaneously weekly (51 patients). The primary end point was low disease activity (LDA) measured with Disease Activity Score‐28 with C‐reactive protein (DAS28‐CRP), and the secondary end point was LDA and remission measured by DAS28‐erythrocyte sedimentation rate (ESR), Clinical Disease Activity Index (CDAI), and Simplified Disease Activity Index (SDAI). Health Assessment Questionnaire Disability Index (HAQ‐DI) response and mean reduction of core set of outcomes from baseline at 12 weeks were also analyzed as secondary end points. In addition, acute‐phase reactants and composite measurements among groups were examined.

Results

LDA in DAS28‐CRP was achieved in 17 (34.7%) tofacitinib patients and 18 (35.3%) MTX patients (p = .95). Fourteen (28.6%) and 11 (21.6%) tofacitinib and MTX patients, respectively, achieved LDA by DAS28‐ESR (p = .42). Tofacitinib and MTX groups achieved LDA similarly in CDAI (36.7% against 37.3%; p = .96) and SDAI (38.8% vs. 39.2%; p = .96). There was no significant difference in achieving remission between the groups. At 12 weeks, tofacitinib reduced ESR and CRP (p < .05). Composite measures and functional status decreased within groups but not between groups (p > .05). Five (13.51%) tofacitinib patients developed hypertension. MTX caused gastrointestinal problems in 12 (30%) individuals. Two MTX (5%) and two tofacitinib (5.4%) patients had increased liver enzymes and renal impairment, respectively. Tofacitinib had 5.4% infection compared with 5% for MTX.

Conclusions

As tofacitinib may be more effective than MTX according to previous reports such as the ORAL Start study, high‐dose MTX (25 mg/week, subcutaneously) used in this study may be as efficacious as tofacitinib in patients with established RA who were DMARD naive or had not received a therapeutic dose of DMARDs. However, adverse effects differed between groups.

Registered on: ClinicalTrials.gov; ID: NCT04464642.