bluuebunny/crossref_metadata_2025 huggingface dataset:
Mammalian promoters are characterised by low occupancy and high turnover of RNA polymerase II
Authors: Chatsirisupachai Kasit , Moene Christina J.I. , Kleinendorst Rozemarijn , Kreibich Elisa , Molina Nacho , Krebs Arnaud
Published: September 2024

The general transcription machinery and its occupancy at promoters are highly conserved across metazoans. This contrasts with the kinetics of mRNA production that considerably differ between model species such asDrosophilaand mouse. The molecular basis for these kinetic differences is currently unknown. Here, we used Single Molecule Footprinting to measure RNA Polymerase II (Pol II) occupancy, the fraction of DNA molecules bound, at promoters in mouse andDrosophilacell lines. Single molecule data reveals that Pol II occupancy is on average 3-5 times more frequent at transcriptionally activeDrosophilapromoters than active mouse promoters. Kinetic modelling of the occupancy states suggests that these differences in Pol II occupancy are determined by the ratio between the transcription initiation and Pol II turnover rates. We used chemical perturbation of transcription initiation to determine Pol II turnover rate in both species. Integration of these data into the model shows that infrequent Pol II occupancy in mammals is explained by the combination of high Pol II turnover and low transcription initiation rates.
Identification of a terpene synthase arsenal using long-read sequencing and genome assembly ofAspergillus wentii
Authors: Olumakaiye Richard , Corre Christophe , Alberti Fabrizio
Published: September 2024

Fungi are talented producers of secondary metabolites with applications in the pharmaceutical and agrochemical sectors.Aspergillus wentiiCBS 141173 has gathered research interest due to its ability to produce high-value norditerpenoid compounds, including anticancer molecules. In this study, we aimed to expand the genomic information available forA. wentiito facilitate the identification of terpenoid biosynthetic genes that may be involved in the production of bioactive molecules. Long-read genome sequencing ofAspergillus wentiiCBS 141173 was conducted using Oxford Nanopore Technologies (ONT) MinION MK1C. In addition, paired-end stranded RNA-seq data from two time points, 7 days and 30 days, was used for functional annotation of the assembled genome. Overall, we assembled a genome of approximately 31.2 Mb and identified 66 biosynthetic gene clusters from the annotated genome. Metabolic extracts ofA. wentiiwere analysed and the production of the bioactive terpenoid asperolide A was confirmed. We further mined the assembled and annotated genome for BGCs involved in terpenoid pathways using a combination of antiSMASH and local BlastP and identified 16 terpene synthases. Phylogenetic analysis was conducted and allowed us to establish relationships with other characterised terpene synthases. We identified two terpene clusters potentially involved in pimarane-like diterpenoid biosynthesis. Finally, the analysis of the 16 terpene synthases in our 7-day and 30-day transcriptomic data suggested that only four of them were constitutively expressed under laboratory conditions. These results provide a scaffold for the future exploration of terpenoid biosynthetic pathways for bioactive molecules inA. wentii. The terpenoid clusters identified in this study are candidates for heterologous gene expression and/or gene disruption experiments. The description and availability of the long-read genome assembly ofA. wentiiCBS 141173 further provides the basis for downstream genome analysis and biotechnological exploitation of this species.
Higher-order and distributed synergistic functional interactions encode information gain in goal-directed learning
Authors: Combrisson Etiennne , Basanisi Ruggero , Neri Matteo , Auzias Guillaume , Petri Giovanni , Marinazzo Daniele , Panzeri Stefano , Brovelli Andrea
Published: September 2024

The ability to create beliefs about the consequences of our actions, also known as goal-directed learning, is a key facet of cognition and it provides the basis for rational decision-making. Goal-directed learning arises from a distributed neural circuit including the prefrontal, posterior parietal and temporal cortices. However, the role of cortico-cortical functional interactions remains unclear. To tackle this question, we combined information decomposition theory with human magnetoencephalography (MEG) and studied whether and how learning signals are encoded through neural interactions. Our findings revealed that 'information gain' - or the decrease in uncertainty regarding the causal relationship between an action and its consequence - is represented within a distributed cortical network, incorporating the visual, parietal, lateral prefrontal, and ventromedial/orbital prefrontal cortices. Remarkably, cortico-cortical interactions encoded information gain in a synergistic manner, beyond what individual regions represented alone. Synergistic interactions encoded information gain at the level of pairwise and higher-order relations, such as triplets and quadruplets. Higher-order synergistic interactions were characterised by long-range relations gravitating over the ventromedial and orbitofrontal cortices, which played a receiving role in the broadcasting of information gain over cortical circuits. Overall, the current study provides evidence that information gain is encoded in both synergistic and higher-order functional interactions, as well as through the broadcasting of information gain signals toward the prefrontal reward circuitry. Moreover, our research offers a new perspective on how information relevant to cognition is encoded and broadcasted within distributed cortical networks and brain-wide dynamics.
Identification of neurodevelopmental organization of the cell populations of juvenile Huntington’s disease using dorso-ventral HD organoids and HD mouse embryos
Authors: Świtońska-Kurkowska Karolina , Kubiś Jakub , Delimata-Raczek Joanna , Krist Bart , Surdyka Magda , Kalinowska-Pośka Żaneta , Piasecki Piotr , Handschuh Luiza , Podkowiński Jan , Rakoczy Magdalena , Samelak-Czajka Anna , Hayden Michael , Caron Nicholas S , Figiel Maciej
Published: September 2024

Huntington’s disease (HD) is a polyglutamine neurodegenerative disease involving pathogenesis within the striatum and cerebral cortex and a neurodevelopmental component, particularly in juvenile HD form (JOHD). We established a fused HD dorsal-ventral system, imitating the cortex and striatum interaction in a single organoid to discover neurodevelopmental impairments at the level of cell populations. We found a range of early pathogenic phenotypes indicating that brain development in HD is affected by impaired neurogenesis. The phenotypes occurred already in early-stage 60-day organoids and the brain of humanized mouse embryos, at time of the beginning of the neurogenesis and choroid plexus development. We demonstrated that HD organoids and HD mouse embryonic brains had gene expression profiles of impaired maturation of neurons and increased expression of genes responsible for proliferation compared to genes responsible for differentiation in control organoids. By using scRNA-seq, the choroid plexus population was highly abundant in HD organoids and embryonic brains. Cortical and choroid plexus cell populations in HD organoids and brains co-expressed genes responsible forHTTfunction (mitotic spindle and cilia). The impaired maturation and the increased occurrence of the choroid plexus populations were mitigated in our compensatory model, mosaic dorsal/ventral (D/V) or V/D HD/control organoids. Finally, we found that TTR protein, a choroid plexus marker, is elevated in the adult HD mouse serum, indicating that TTR may be a promising marker for detecting HD. In summary, the fused dorso-ventral HD organoids identify a spectrum of neurodevelopmental features, including increased proliferation and delayed cell maturation. We demonstrate that the choroid plexus population is characteristic of aberrant HD neurodevelopment, and contains TTR marker, which can be translated as a blood marker in HD.
Adrenergic signaling gates astrocyte responsiveness to neurotransmitters and control of neuronal activity
Authors: Guttenplan Kevin A. , Maxwell Isa , Santos Erin , Borchardt Luke A. , Manzo Ernesto , Abalde-Atristain Leire , Kim Rachel D , Freeman Marc R.
Published: September 2024

How astrocytes regulate neuronal circuits is a fundamental, unsolved question in neurobiology. Nevertheless, few studies have explored the rules that govern when astrocytes respond to different neurotransmittersin vivoand how they affect downstream circuit modulation. Here, we report an unexpected mechanism inDrosophilaby which G-protein coupled adrenergic signaling in astrocytes can control, or “gate,” their ability to respond to other neurotransmitters. Further, we show that manipulating this pathway potently regulates neuronal circuit activity and animal behavior. Finally, we demonstrate that this gating mechanism is conserved in mammalian astrocytes, arguing it is an ancient feature of astrocyte circuit function. Our work establishes a new mechanism by which astrocytes dynamically respond to and modulate neuronal activity in different brain regions and in different behavioral states.
Localized translation oferm-1contributes to ERM-1 function in theC. elegansembryo
Authors: van der Salm Elise , Koelewijn Esther , van der Maas Erica , Eeken Max , Ruijtenberg Suzan
Published: September 2024

Translation of mRNAs into proteins is a key step in decoding the information stored in the genome. Localized translation ensures that proteins are expressed where needed, which is important for cell-specific protein expression, the establishment of cellular protein gradients, and the creation of protein hotspots within different cellular compartments. Although localized translation is believed to be important for cell fate determination and organismal development, our understanding of localized translation in the context of living animals is limited, as few methods that allow direct visualization and measurement of translation exist. We adapted the SunTag-based single-molecule translation imaging system for use in Caenorhabditis elegans and showed the dynamics and importance of localizederm-1translation during development. We founderm-1translation to be enriched at the plasma membrane, overlapping with the localization and function of the encoded membrane-cytoskeleton linker ERM-1. Re-localizingerm-1translation to nuclear pores disrupts the function of ERM-1 protein, particularly its role in linking the actin cytoskeleton to the membrane. Our work demonstrates the power of translation imaging and highlights the importance of localized translation inC. elegansdevelopment.
Discovery of dehydroamino acids and their crosslinks in Tau and other aggregating proteins of Alzheimer’s disease
Authors: Markovich Samuel W. , Frey Brian L. , Scalf Mark , Shortreed Michael R. , Smith Lloyd M.
Published: September 2024

Background

Alzheimer’s disease (AD) is characterized by accumulation of two types of protein aggregates, senile plaques and neurofibrillary tangles, which strongly contribute to the pathogenesis of the disease. Senile plaques consist primarily of aggregated amyloid-ß, while neurofibrillary tangles form via aggregation of the protein Tau, as well as other microtubule-associated proteins such as CRMP2. Posttranslational modifications have been hypothesized to contribute to the initial aggregation events that lead to SPs and NFTs. Dehydroamino acids (DHAAs) are posttranslational modifications rarely observed in humans and have not previously been reported in AD. DHAAs arise from the eliminylation of serine, threonine, or cysteine, yielding a double bond with distinct molecular geometry and reactivity. Their geometry can produce secondary structure rearrangements, such as those seen in senile plaque and neurofibrillary tangle formation, while their reactivity can cause intramolecular or intermolecular (protein-protein) crosslinking. We hypothesized that this modification might be present in protein aggregation-associated neurodegenerative disorders like AD.

Methods

We performed mass spectrometry-based bottom-up proteomics on the sarkosyl-insoluble (protein aggregate-enriched) material from ten AD brains and three age-matched controls. Identifications of DHAA-mediated crosslinked peptides were validated using both an isotopic labeling strategy and spike-in experiments employing synthetic crosslinked peptide standards. Similar findings were obtained in searches of publicly available proteomic datasets from AD and control brains.

Results

We identified 412 sites of DHAA modification in 184 proteins, with the highest prevalence in the neurofibrillary tangle-forming proteins Tau and CRMP2. Comparison with results of previous protein aggregate interactomics studies show that proteins containing the DHAA modification are more highly associated with protein aggregates than are proteins containing any other individual posttranslational modification. We further observed 11 protein crosslinks arising from DHAAs, including three from the Tau protein. Label free quantification showed that Tau crosslinks are an order of magnitude more prevalent in AD samples than in age-matched controls.

Conclusions

Dehydroamino acids and their derivatives are prevalent modifications in the Alzheimer’s disease brain proteome. These modifications give rise to protein crosslinks which may contribute to protein aggregation processes.
A membrane-associated conveyor belt controls the rotational direction of the bacterial type 9 secretion system
Authors: Trivedi Abhishek , Miratsky Jacob A. , Henderson Emma C. , Singharoy Abhishek , Shrivastava Abhishek
Published: September 2024

Many bacteria utilize the type 9 secretion system (T9SS) for gliding motility, surface colonization, and pathogenesis. This dual-function motor supports both gliding motility and protein secretion, where rotation of the T9SS plays a central role. Fueled by the energy of the stored proton motive force and transmitted through the torque of membrane-anchored stator units, the rotary T9SS propels an adhesin-coated conveyor belt along the bacterial outer membrane like a molecular snowmobile, thereby enabling gliding motion. However, the mechanisms controlling the rotational direction and gliding motility of T9SS remain elusive. Shedding light on this mechanism, we find that in the gliding bacteriumFlavobacterium johnsoniae, deletion of the C-terminus of a conveyor belt protein GldJ controls, and in fact, reverses the rotational direction of T9SS from counterclockwise to clockwise thus suggesting that the interface between the conveyor belt protein GldJ and the T9SS ring protein GldK plays an important role in controlling the directionality of T9SS. Combined with MD simulation of the T9SS stator units GldLM, we suggest a ‘tri-component gearset’ model where the conveyor belt controls the rotational direction of its driver, the T9SS, thus providing adaptive sensory feedback to influence the motility of the gliding bacterium.
Distinct classes of antidepressants commonly act to shape pallidal structure and function in mice
Authors: Abe Yoshifumi , Sugiura Yuki , Maeda Rae , Taira Shu , Yoshida Keisuke , Ibi Daisuke , Hashimoto Kenji , Yagishita Sho , Tanaka Kenji F
Published: September 2024

Antidepressants, including selective serotonin reuptake inhibitors (SSRIs), ketamine, and psilocybin, are effective for treating depression despite their distinct modes of action. We hypothesized that their underlying mechanisms of action are shared. Mice were administered escitalopram (15 mg/kg daily for 3 weeks, 21 mice), R-/S-/racemic ketamine (10 mg/kg, single injection, 21–22 mice), or psilocin (1 mg/kg, single injection, 22 mice).

Electroconvulsive stimulation (9 times for 3 weeks, 12 mice) and saline were used as controls. After structural magnetic resonance imaging (MRI) of fixed brains, voxel-based morphometry was conducted to assess brain-wide volumetric changes. A single dose of ketamine or psilocin was sufficient to induce MRI-detectable volume changes. All antidepressants increased the volume in the nucleus accumbens, ventral pallidum, and external globus pallidus and decreased the volume in the mediodorsal thalamus, which is distinct from the changes observed with electroconvulsive stimulation. We identified microstructural and molecular changes using super-resolution microscopy and imaging mass spectrometry, respectively. Pallidal volumetric increases were associated with hypertrophy of striatal medium spiny neuron terminals and increased γ-aminobutyric acid (GABA) content. We experimentally addressed whether the overexpression of the vesicular GABA transporter (VGAT) reproduced these changes. The overexpression of striatal VGAT reproduced these structural changes. R-ketamine, SR-ketamine, and psilocin induced more pronounced ventral pallidum hypertrophy, and SSRIs and S-ketamine induced globus pallidus hypertrophy. We discovered shared pallidum-centered structural and molecular changes among various antidepressants, which possibly potentiate the striato-pallidial inhibition associated with antidepressant action. Our data support visualizing antidepressant responses using pallidum-centered GABA MR spectroscopy or structural MRI.
microRNA-138-5p suppresses excitatory synaptic strength at the cerebellar input layer
Authors: Delvendahl Igor , Daswani Reetu , Winterer Jochen , Germain Pierre-Luc , Uhr Nora Maria , Schratt Gerhard , Müller Martin
Published: September 2024

MicroRNAs are small, highly conserved non-coding RNAs that negatively regulate mRNA translation and stability. In the brain, microRNAs contribute to neuronal development, synaptogenesis, and synaptic plasticity. The microRNA 138-5p (miR-138-5p) controls inhibitory synaptic transmission in the hippocampus and is highly expressed in cerebellar excitatory neurons. However, its role in cerebellar synaptic transmission remains unkwown. Here, we investigated excitatory transmission within the cerebellum in mice expressing a sponge construct that sequesters endogenous miR-138-5p. Mossy fiber stimulation-evoked excitatory postsynaptic currents (EPSCs) in granule cells were significantly larger compared with controls. Furthermore, we observed larger miniature EPSC amplitudes, suggesting increased postsynaptic AMPA receptor numbers. High-frequency train stimulations revealed enhanced short-term depression following miR-138-5p downregulation. Together with computational modelling, this suggests a negative regulation of presynaptic release probability. Overall, our results demonstrate that miR-138-5p suppresses synaptic strength through pre- and postsynaptic mechanisms, providing a powerful mechanism for tuning excitatory synaptic input into the cerebellum.
Shigella flexnerievades LPS ubiquitylation through IpaH1.4-mediated degradation of RNF213
Authors: Naydenova Katerina , Boyle Keith B. , Pathe Claudio , Pothukuchi Prathyush , Crespillo-Casado Ana , Scharte Felix , Hammoudi Pierre-Mehdi , Otten Elsje G. , Randow Felix
Published: September 2024

The evolutionary arms race between pathogens and hosts has resulted in pathogens acquiring diverse adaptive countermeasures that antagonize host immunity. Ubiquitylation of lipopolysaccharide (LPS) on cytosol-invading bacteria by the E3 ligase RNF213 creates ‘eat-me’ signals for antibacterial autophagy but whether and how cytosol-adapted bacteria avoid LPS ubiquitylation remains poorly understood. Here we show thatShigella flexneri, a professional cytosol-dwelling enterobacterium, actively antagonizes LPS ubiquitylation through IpaH1.4, a secreted effector protein with ubiquitin E3 ligase activity. IpaH1.4 binds to the LPS E3 ubiquitin ligase RNF213, ubiquitylates it, and targets it for degradation by the proteasome, thus preventing LPS ubiquitylation. To understand how IpaH1.4 recognizes RNF213, we determined the structure of their complex using cryogenic electron microscopy. The specificity of the interaction is achieved via the leucine rich repeat of IpaH1.4, which binds the RING domain of RNF213 by hijacking the conserved RING interface required for binding of ubiquitin-charged E2 enzymes. Interestingly, IpaH1.4 also targets the E3 ligase LUBAC - required for the synthesis of M1-linked ubiquitin chains on cytosol-invading bacteria downstream of RNF213 – as well as multiple other E3 ligases involved in inflammation and immunity – through binding to the E2-interacting face of their RING domains. We conclude that IpaH1.4 has evolved to antagonize multiple anti-bacterial and pro-inflammatory host E3 ligases.
Synthesis, non-spherical structure refinement and Hirshfeld surface analysis of racemic 2,2′-diisobutoxy-1,1′-binaphthalene
Authors: Coulibaly Pénayori Marie-Aimée , Ziki Eric , Bisseyou Yvon Bibila Mayaya , Camara Tchambaga Etienne , Coulibaly Souleymane , Sissouma Drissa
Published: September 2024

In the racemic title compound, C28H30O2, the naphthyl ring systems subtend a dihedral angle of 68.59 (1)° and the molecular conformation is consolidated by a pair of intramolecular C—H...π contacts. The crystal packing features a weak C—H...π contact and van der Waals forces. A Hirshfeld surface analysis of the crystal structure reveals that the most significant contributions are from H...H (73.2%) and C...H/H...C (21.2%) contacts.
Corporate governance and financial performance: the case of English NHS hospitals
Authors: Achiro Laura Obwona , Tauringana Venancio , Alta'any Mohammad
Published: September 2024

Purpose

Hospitals’ corporate governance (CG) mechanisms oversee critical operational issues and evaluate the outcomes. This paper investigates the impact of CG (i.e. board size, board independence, board expertise, board meetings, board gender diversity, CEO gender, and academic directors) on the financial performance of English National Health Service (NHS) hospitals and separately by hospital type (i.e. trusts and foundation trusts).

Design/methodology/approach

The sample includes 128 NHS hospitals. The data were collected through document analysis and archival work from annual hospital reports from 2014 to 2018.

Findings

The findings indicate that board expertise, board meetings, board diversity, CEO gender, and academic directors significantly and negatively affect NHS hospitals’ financial performance. For NHS trusts, the results reveal that board expertise, board diversity, and CEO gender have a significant negative effect, while for NHS foundation trusts, only CEO gender has a significant negative impact.

Originality/value

Overall, this study contributes to the literature on the healthcare system. It holds significant practical implications for hospital governance and has important implications for theories.
Impact of the Israel–Hamas conflict on financial markets of MENA region – a study on investors’ reaction
Authors: Yudaruddin Rizky , Lesmana Dadang , Yudaruddin Yanzil Azizil , Ekşi̇ İbrahim Halil , Başar Berna Doğan
Published: September 2024

Purpose

This study aims to examine market reactions to the Israel–Hamas conflict in neighboring countries, particularly focusing on the Middle East North Africa (MENA) region.

Design/methodology/approach

The study adopts an event study methodology, employing average abnormal return (AAR) and cumulative abnormal return as measures to assess market reactions. The sample for this study comprises 1,314 companies, with October 9, 2023, identified as the event day for analysis.

Findings

The results of our study indicate that countries in close proximity to Israel and Palestine encountered detrimental effects on their capital markets, as evidenced by negative responses observed across various sectors. Our analysis also reveals that countries in the midst of conflict, particularly Israel, experienced a decrease in their stock markets across various sectors, with the exception of materials and real estate. In addition, our investigation reveals disparities in market responses according to different categories of company size.

Originality/value

This research is the first to study market reactions to Israel–Hamas in the MENA region at the company level.
Wellness tourism destination loyalty formation: the role of mental health and eudaimonic well-being
Authors: Chua Bee-Lia , Kim Seongseop (Sam) , Ling Esther Sii Wei , Xu Yuchen , Ryu Hyungseo Bobby , Han Heesup
Published: September 2024

Purpose

Wellness tourism is growing in importance as increasing numbers of travelers place a priority on their health and well-being by traveling. This study examined the relationships between wellness tourism destination attributes, perceived quality, perceived mental health, eudaimonic well-being, overall satisfaction and behavioral loyalty to corroborate a model explaining wellness tourism destination loyalty in Thailand.

Design/methodology/approach

The conceptual model of this study was examined using a survey research design. The survey questionnaire was distributed to Chinese tourists who had previously traveled to Thailand and engaged in wellness tourism activities during their trip.

Findings

The findings revealed that healthful food choices, core facilities and staff service significantly influenced perceived quality. This perceived quality was a crucial factor in determining perceived mental health, which in turn impacted eudaimonic well-being. Overall satisfaction was directly influenced by perceived quality, perceived mental health and eudaimonic well-being. Additionally, perceived quality had a direct effect on behavioral loyalty.

Practical implications

With the growing global interest in wellness and travel, this study offers valuable insights for tourism marketers in Thailand to enhance their wellness tourism strategies. Tourism organizations should emphasize the quality of food, facilities and staff service to attract wellness-oriented travelers.

Originality/value

This study highlights the interconnectedness of perceived quality, good mental health and eudaimonic well-being. High-quality experiences contribute to improved mental health and in turn enhance eudaimonic well-being.
Understanding underdog brand positioning effects among emerging market consumers: a moderated mediation approach
Authors: Patel Jayesh D. , Trivedi Rohit , Malhotra Svablum , Jagani Khyati
Published: September 2024

Purpose

This study aims to explore the underdog brand biography dimensions that emerging-country consumers identify with (Study 1) and attempts to uncover the effects of these dimensions on brand affinity and purchase intention moderated by self-identity and brand trust (Study 2).

Design/methodology/approach

Study 1, using data from 359 young Indians, reveals three underlying dimensions integral to underdog brand biography in emerging markets. Study 2 uses an experimental setup with a single-factorial design among 332 young Mexican consumers to investigate the direct effects of three identified underdog brand biography dimensions on purchase intention, mediated by brand affinity and moderated by consumer self-identity and brand trust.

Findings

Study 1 reveals three dimensions underlying underdog brand biographies: unfavorable circumstances, striving in adversities and passion, and persistent will to succeed. Study 2 reveals that consumers with higher self-identity demonstrate greater purchase intentions for an underdog brand than a top dog one.

Practical implications

The results indicate that marketers can successfully use underdog narratives to influence consumer decision-making, thereby increasing brand affinity and purchase intention.

Originality/value

This study delineates the link between different dimensions of underdog brand biographies with brand affinity and purchase intention in emerging countries and builds on the understanding of the moderating role played by self-identity and brand trust.
To acknowledge or conceal: an exploratory study on designers' self-determination factors and attitudes toward artificial intelligence participation in their works
Authors: Jiang Qianling , Qian Jue , Zang Yong
Published: September 2024

Purpose

The rapid development and widespread application of artificial intelligence tools have raised concerns about how designers are embracing these technologies. This study investigates the factors influencing designers' behavioral intention to use and disclose the use of generative artificial intelligence.

Design/methodology/approach

A quantitative research approach was employed, designing a structured questionnaire based on Self-Determination Theory to assess the impact of various psychological and social dimensions. The questionnaire included dimensions such as autonomy, competence, relatedness, social influence, value fit and social innovativeness. A Partial Least Squares Structural Equation Modeling analysis was conducted on 309 valid responses from diverse design fields.

Findings

Competence and relatedness are significant factors influencing designers' continuance intention to use generative artificial intelligence. Although autonomy does not significantly affect continuance intention, it plays a crucial role in the decision to disclose artificial intelligence participation. Social influence and value fit significantly shape autonomy, competence and relatedness, while the impact of social innovativeness is relatively limited.

Originality/value

This study clarifies the factors influencing designers' continuance intention and disclosure of generative artificial intelligence tools from both individual and social dimensions, enhancing the understanding of the relationship between designers and generative artificial intelligence tools. It provides valuable insights for the development of artificial intelligence technology and the future trends in the design industry, offering significant theoretical and practical value.
Typology of esports crowdfunding investors
Authors: Oh Taeyeon , Lee Seomgyun
Published: September 2024

Purpose

Online fundraising has become a rapidly growing alternative business financing method for esports. Despite this, a lack of attention has been given to its fans' motivations for participating in crowdfunding (CF) projects or behavioral intentions for spectatorship. To address this, the present study (1) categorizes esport CF investors' motivations based on the big five personality traits and (2) compares whether motivations and behavioral intentions for esports spectatorships vary depending on each group.

Design/methodology/approach

We applied K-means clustering analysis to classify investors. ANOVA was used to verify whether there were differences in CF motivations and behavioral intentions.

Findings

The study identified six distinct investor segments. Overall, esports CF investors showed high agreeableness and conscientiousness with low neuroticism. Fanatic fans were the most motivated and had the highest spectatorship intentions, driven by strong openness. In contrast, recognition seekers and charity donors exhibited the lowest viewing intentions. Entertainment seekers were highly motivated by excitement and aesthetics, linking CF participation to a strong desire to watch events. Despite higher neuroticism, reward hunters also showed significant viewing intentions, driven by drama and aesthetics. These findings highlight the diverse motivations and their influence on esports spectatorship.

Originality/value

This study investigates the motivations and behavioral intentions of CF investors and spectatorship, which has substantive theoretical and managerial implications for the business of esports.
Is pollen limitation linked to phenotypic selection on floral traits in the carnivorous plant Pinguicula moranensis (Lentibulariaceae)?
Authors: Villegas Sara Gabriela , Domínguez César , Fornoni Juan , Ospina‐Garcés Sandra M. , Alcalá Raúl Ernesto
Published: September 2024

In carnivorous plants, the fitness impacts of phenotypic variation in traits involved in prey attraction and capture have been well documented. However, floral traits could also contribute to the fitness of carnivorous plants. Pinguicula moranensis is a carnivorous plant that presents colorful zygomorphic flowers, which suggests some degree of specialization in its interactions with pollinators. We first tested pollen limitation experimentally by comparing the fruit set in plants that were manually cross‐pollinated with those that were pollinated naturally. Then, using a path analysis approach, we explored the effects of plant size and floral traits (corolla shape, corolla size, spur length, nectar guide size, and stalk length) on fitness (seed number per fruit). We performed two independent path analyses—one with the naturally pollinated plants and the other with the hand pollinated plants—to consider the impacts of these variables with and without the pressure of pollinator attraction. We expected stronger selection on floral traits in naturally pollinated plants. We found evidence of pollen limitation in the fruit set of the naturally pollinated group, suggesting that pollinator availability could impose selective pressures. The path analyses showed a marked direct positive effect of rosette size on plant fitness in both groups. The direct effects of all floral traits had similar magnitudes between the naturally pollinated and hand pollinated plants, except for corolla shape that showed higher coefficients in the first group. Thus, although we evidenced pollen limitation, our prediction about the role of pollinators as selective agents of floral traits in P. moranensis was barely supported.
Review article: Strategies to improve emergency department care for adults living with disability: A systematic review
Authors: Newman Bronwyn , Cheek Colleen , Richardson Lieke , Gillies Donna , Hutchinson Karen , Austin Elizabeth , Murphy Margaret , Testa Luke , Rojas Christina , Raggett Louise , Dominello Amanda , Smith Kylie , Clay‐Williams Robyn
Published: September 2024

Equitable access means that timely, sensitive and respectful treatment is offered to all people. Adults with disability access ED care more frequently than the general population. However, in Australia and internationally, people with disability experience poorer healthcare access and outcomes than the general population. There is acknowledgement that ED environments and processes of care could be better designed to promote equitable access, so as not to further disadvantage, disable and create vulnerability. This systematic review aimed to locate and describe evaluated strategies implemented to improve care for people with disability (aged 18–65 years) in the ED. Four databases were searched from inception to June 2024. 1936 peer‐reviewed papers were reviewed by pairs of independent reviewers. Four studies met our inclusion criteria, demonstrating the limited peer‐reviewed literature reporting on evaluated strategies to improve ED care for adults aged 18–65 years. Three studies focused on the needs of people with intellectual disability, and one created a specific treatment pathway for people experiencing status epilepticus. No studies evaluated across patient experience, patient outcomes, system performance and staff experience, with limited evaluation of patient outcomes and system performance measures. We have referenced helpful resources published elsewhere and drawn from our previous reviews of ED care to provide guidance for the development and evaluation of targeted initiatives.
Are histomorphological patterns a predictor for survival in uveal melanoma patients with hepatic metastases undergoing hepatic artery infusion chemotherapy?
Authors: Steinberg‐Vorhoff Hannah L , Ting Saskia C , Zensen Sebastian , Ludwig Johannes M , Li Yan , Richly Heike , Grüneisen Johannes , Siveke Jens T , Theysohn Jens M , Schaarschmidt Benedikt M
Published: September 2024

Introduction

In uveal melanoma (UM) patients with hepatic metastases, hepatic artery infusion chemotherapy (HAIC) is a viable, palliative treatment option. To evaluate the impact of two histomorphological patterns (spindle cell vs. epithelioid) of liver metastases on median overall survival (mOS) in UM patients undergoing HAIC.

Methods

A retrospective analysis with 60 UM patients (29 females, mean age: 61.6 ± 12.1 years) with hepatic metastases was performed. Histomorphological patterns in metastases were analysed and classified as either predominant spindle cell or epithelioid pattern. mOS between both patient groups was analysed using Kaplan–Meier curves and the log‐rank test.

Results

In 73.3% (44/60) of the metastases, a predominant epithelioid pattern, in 21.7% (13/60) a predominant spindle cell pattern, and in 5% (3/60) other patterns were found. No significant differences between patients with an epithelioid (mOS: 14.2 months, 95% CI: 8.8–19.6) and a spindle cell pattern (mOS: 14.4 months, 95% CI: 4.3–24.5) were detected by the log‐rank test, χ2(2) = 0.22, P = 0.881.

Conclusion

Histomorphological patterns of UM metastases do not seem to be a predictor for mOS in UM patients undergoing HAIC.
Prevalence and etiology of ventilator‐associated pneumonia during the COVID‐19 pandemic in Denmark: Wave‐dependent lessons learned from a mixed‐ICU
Authors: Grzywacz Joanna , Ahlström Magnus G. , Benfield Thomas , Berg Ronan M. G. , Plovsing Ronni R. , Ronit Andreas
Published: September 2024

Background

Ventilator‐associated pneumonia (VAP) may be a particular concern in patients with severe coronavirus disease 2019 (COVID‐19). We aimed to determine the prevalence and etiology of VAP in critically ill COVID‐19 patients in a Danish intensive care unit (ICU) during the first three waves of the COVID‐19 pandemic and to study associations between dexamethasone (DXM) use and development of VAP.

Methods

In an observational single‐center study patients were retrospectively screened for VAP including causative pathogens, use of DXM and commonly used antibiotics. Diagnosis of VAP required invasive mechanical ventilation (IMV) >48 h with presence of a new bacterial agent and clinical signs of infection. For analysis, common descriptive statistics were applied. Cox proportional hazards models were used to analyze the association between DXM use and VAP.

Results

VAP was detected in 53/119 (44.5%) mechanically ventilated patients across all three COVID‐19 waves. Median length of IMV for VAP patients was 24 [15–41] days, and 3 out of 4 were males. VAP was most prevalent (47.0%) during the second wave. Common pathogens included Klebsiella pneumoniae (24.5%), Enterobacter aerogenes (17.0%) and Pseudomonas aeruginosa (13.2%), Staphylococcus aureus (13.2%), and Escherichia coli (13.2%). A change from Gram‐negative bacteria only to a combination of Gram‐positive and Gram‐negative bacteria was observed in the second wave compared to first. Use of DXM was not associated with VAP (adjusted hazard ratio 1.63 95% CI: 0.84–3.17).

Conclusion

The prevalence of VAP was high across all three COVID‐19 waves and showed a different distribution of pathogens between the first and second wave. Use of DXM was not associated with VAP development. Further and larger studies are needed to understand the risk factors associated with VAP in patients with COVID‐19.
Concentration‐QTc analysis of soticlestat in healthy adults: An alternative to a thorough QT study
Authors: Yin Wei , Dote Nobuhito , Fukase Hiroyuki , Imazaki Manami , Shimizu Kohei , Takeda Shinichi , Darpo Borje , Xue Hongqi , Asgharnejad Mahnaz
Published: September 2024

Aim

This study aimed to examine the cardiac and overall safety and pharmacokinetic (PK) profiles of soticlestat (TAK‐935), an oral, first‐in‐class selective cholesterol 24‐hydroxylase inhibitor.

Methods

Data came from a randomised, phase 1 study of soticlestat in 33 healthy Japanese adults (NCT04461483); 24 adults in Part 1 (single‐dose soticlestat 200‐1200 mg or placebo) and 9 in Part 2 (soticlestat 100‐300 mg twice daily or placebo for 21 days). PK sample collection was paired with 12‐lead electrocardiogram data from continuous Holter recordings. The concentration‐QTc relationship was analysed using a linear mixed‐effects model. QTc prolongation safety margins were determined for two scenarios of calculated high clinical exposures: scenario 1 (NCT05064449) involved coadministration of single‐dose soticlestat 300 mg with itraconazole or mefenamic acid and scenario 2 (NCT05098054) involved single‐dose soticlestat 300 mg administration in participants with mild/moderate hepatic impairment (implementing a 3‐fold dose reduction for moderate severity).

Results

Based on concentration‐QTc analysis, placebo‐corrected change‐from‐baseline QT values (90% confidence intervals), corrected for heart rate (Fridericia's method), were 0.94 ms (−2.35, 4.23) for soticlestat and 0.63 ms (−3.15, 4.41) for its N‐oxide metabolite plasma concentrations at therapeutic doses (soticlestat 300 mg twice daily); safety margins were >2‐fold for scenarios of calculated high clinical exposures. No (Part 1) and five (83.3%; Part 2) participants experienced treatment‐emergent adverse events (all mild).

Conclusion

There was no evidence for QT prolongation with soticlestat at therapeutic doses or in two scenarios of high clinical exposures, which resulted in regulatory agencies waiving requirements of a thorough QT study. Safety/PK findings aligned with previous soticlestat clinical studies.
Population pharmacokinetics of long‐term hydroxychloroquine therapy in patients with rheumatic diseases
Authors: Yang Chunlan , Deng Yiyun , Liu Hui , Song Shuai , Jiu Jiatao , Pan Menglu , Xia Quan , Xu Dujuan , Wu Ye , Su Yong
Published: September 2024

Aims

Hydroxychloroquine (HCQ) is recommended for the long‐term treatment of rheumatic diseases such as rheumatoid arthritis and systemic lupus erythematosus. Given the complex process of HCQ metabolism and individual physiological differences, the metabolic profile of HCQ after long‐term administration is unknown. This study aimed to establish a population pharmacokinetic model for long‐term HCQ treatment in patients with rheumatic diseases and to identify the factors influencing HCQ metabolism.

Methods

This study included 274 HCQ whole‐blood trough concentration data points from 203 patients with rheumatic diseases, all of whom had taken HCQ for more than 6 months, with a median duration of 36 months. A nonlinear mixed‐effects model was derived to establish a population pharmacokinetic model, and potential influencing factors were investigated. Different covariates were used to simulate the optimal dose.

Results

The final model describing the HCQ blood concentration–time profile was a compartmental model with first‐order absorption. The estimated values for apparent clearance and volume of distribution were 16.4 L/h and 1220 L, respectively. The clearance of HCQ gradually increased with increasing dosing regimens and weight gain. Monte Carlo simulations were used to determine the optimal dosage regimens for patients with different body weights and drug durations. The simulation results revealed that an initial dose of 5 mg/kg was appropriate.

Conclusions

We developed a population pharmacokinetic model for long‐term HCQ therapy in patients with rheumatic diseases. HCQ clearance from whole blood increased progressively with increasing duration of drug administration.
Targeted proteomics profiling reveals valuable biomarkers in the diagnosis of primary immune thrombocytopaenia
Authors: Jiang Yizhi , Li Jizhe , Huang Jun , Zhang Zichan , Liu Xiaocen , Wang Nana , Huang Chen , Wang Ran , Zhang Lanxin , Han JingJing , Bai Xia , Huang Dongping , Zhou Lu
Published: September 2024

The lack of biomarkers for accurate diagnosis and prognosis is a major clinical challenge of primary immune thrombocytopaenia (ITP). Using an Olink proteomics platform with a 92 immune response‐related human protein panel, we analysed plasma samples from ITP patients (ITP, n = 40), patients with thrombocytopaenia secondary to other causes (Non‐ITP, n = 19) and healthy controls (NC, n = 18), of a discovery cohort as well as a validation cohort (ITP, n = 36; NC, n = 20). A total of 10 differentially expressed proteins (DEPs) were identified in the ITP group compared with the non‐ITP and NC groups of the discovery cohort. These include CXCL11, GZMH, ARG1, TGF‐β1, ANGPT1, CXCL12, CD40‐L, PDGF subunit B, IL4 and TNFSF14. Furthermore, least absolute shrinkage and selection operator regression analysis showed some of these DEPs, such as CXCL11, TGF‐β1, ARG1 and GZMH to be significant in differentiating between patients with ITP and healthy controls (validation area under the curve = 0.87). The analysis demonstrated that the ITP group has a specific proteomic profile relative to non‐ITP and NC groups. In summary, we report for the first time that Olink precision proteomics can specifically detect up‐regulated inflammatory proteins as potential diagnostic biomarkers for ITP.
Vertebrate seed predation can limit recruitment of later‐successional species in tropical forest restoration
Authors: Joyce Francis H. , Ramos Brianna M. , Zahawi Rakan A. , Holl Karen D.
Published: September 2024

The effects of vertebrate seed predation on the regeneration of restored forests are not well understood because most past studies have focused on seed predation within the first few years after restoration and have measured seed removal without quantifying subsequent seedling establishment of seeds that avoid predation. Quantifying the establishment of seeds that escape predation in restored forests at later stages of regrowth is crucial for anticipating longer‐term recovery trajectories. Here, we evaluated the potential role of vertebrate seed predators in limiting recruitment of later‐successional tree species in nine forests actively restored ≥15 years prior and in four paired remnant forest fragments embedded in an agricultural landscape in southern Costa Rica. We conducted seed addition experiments with four tree species inside and outside vertebrate exclosures and used camera trapping to detect seed predators. To determine the fate of seeds that avoided predation, we also measured seedling establishment after 1 year, given that other mortality factors may compensate in the absence of vertebrate seed predation. We detected two species of birds and five species of granivorous mammals removing seeds. Seed tagging indicated that most removal resulted in predation. For three of the four tree species tested, vertebrate seed predation reduced seedling establishment. The magnitude of this effect depended on species' susceptibility to other causes of mortality during the seed‐to‐seedling transition. Our study demonstrates that vertebrate seed predators can substantially reduce later‐successional seedling recruitment in restored forests and should be considered alongside dispersal limitation and microsite conditions as factors slowing forest recovery.

Abstract in Spanish is available with online material.
The association between wet work and hand eczema in the Dutch general population: Application of a job exposure matrix to the lifelines cohort study
Authors: Brands Marjolein J. , Loman Laura , Lund Tamara T. , Flachs Esben M. , Bültmann Ute , Schuttelaar Marie L. A.
Published: September 2024

Background

Studies on wet work and hand eczema (HE) frequently rely solely on self‐reports regarding wet work.

Objectives

To assess the association between wet work and moderate‐to‐very‐severe HE, within the Dutch general population, by using a (sex‐specific) job exposure matrix (JEM).

Methods

Within the Lifelines Cohort Study, participants with self‐reported moderate‐to‐very‐severe HE at worst in the past year were linked to data from the Danish (sex‐specific) wet work JEM, a tool that links occupations with wet work indices (including duration and probability of glove use, wet hands and total wet work for at least 2 and 4 h/working day).

Results

In total, 56 978 (41.9%) participants were included. The multivariate binary logistic regression analyses showed significant associations between all facets of wet work and moderate‐to‐very‐severe HE. When using the sex‐specific JEM, significant associations were found in females, but not in males.

Conclusions

This study is the first to use a wet work‐specific JEM in a general population sample, and found positive associations between wet work and HE. The sex‐specific findings should be interpreted with caution, due to limitations inherent in using a JEM, and should be further explored with observational studies, with a focus on duration, frequency, and exposure type.