bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional differentiation of Human Dental Pulp Stem Cells into neuron-like cells exhibiting electrophysiological activity
Authors: Pardo-Rodríguez B. , Baraibar A.M. , Manero-Roig I. , Luzuriaga J. , Salvador-Moya J. , Polo Y. , Basanta-Torres R. , Unda F. , Mato S. , Ibarretxe G. , Pineda J.R.
Published: October 2024

Background

Human dental pulp stem cells (hDPSCs) constitute a promising alternative for central nervous system (CNS) cell therapy. Unlike other human stem cells, hDPSCs can be differentiated, without genetic modification, to neural cells that secrete neuroprotective factors. However, a better understanding of their real capacity to give rise to functional neurons and integrate into synaptic networks is still needed. For that,ex vivodifferentiation protocols must be refined, especially to avoid the use of fetal animal serum.

Methods

In this study, we sought to improve existing differentiation protocols for obtaining functional neuron-like cells from hDPSCs. We compared the effects of the absence or presence of fetal serum during the initial expansion phase as a step prior to switching cultures to neurodifferentiation media. We improved hDPSC neurodifferentiation by adding retinoic acid (RA) and potassium chloride (KCl) pulses for 21 or 60 days and characterized the results by immunofluorescence, digital morphometric analysis, RT-qPCR and electrophysiology.

Results

We found that neural markers like Nestin, GFAP, S100β and p75NTRwere expressed differently in neurodifferentiated hDPSC cultures depending on the presence or absence of serum during the initial cell expansion phase. In addition, hDPSCs previously grown as spheroids in serum-free medium exhibitedin vitroexpression of neuronal markers such as doublecortin (DCX), neuronal nuclear antigen (NeuN), Ankyrin-G and MAP2 after neurodifferentiation. Presynaptic vGLUT2, Synapsin-I, and excitatory glutamatergic and inhibitory GABAergic postsynaptic scaffold proteins and receptor subunits were also present in these neurodifferentiated hDPSCs. Treatment with KCl and RA increased the amount of both voltage-gated Na+and K+channel subunits in neurodifferentiated hDPSCs at the transcript level. Consistently, these cells displayed voltage-dependent K+and TTX-sensitive Na+currents as well as spontaneous electrophysiological activity and repetitive neuronal action potentials with a full baseline potential recovery.

Conclusion

Our study demonstrates, for the first time, that hDPSCs can be differentiated to neuronal-like cells that display functional excitability and thus evidence the potential of these easily accessible human stem cells for nerve tissue engineering. Our results highlight the importance of choosing an appropriate culture protocol to successfully neurodifferentiate hDPSCs.
Epigenetic modulation of RIPK3 by Transglutaminase 2-dependent serotonylation of H3K4me3 affects necroptosis
Authors: Vecchio Alessio , Colasuonno Fiorella , Bellanca Veronica , Pitolli Consuelo , Occhigrossi Luca , Ciccarone Fabio , D’Eletto Manuela , Sano Federica Di , Pagliarini Vittoria , Sette Claudio , Piacentini Mauro , Rossin Federica
Published: October 2024

The receptor interacting protein kinase 3 (RIPK 3) is the main player in the activation of necroptosis, a pro-inflammatory regulated cell death modality induced by many different stimuli. RIPK3 is epigenetically regulated by DNA methylation and can be expressed when its promoter is associated with H3K4me3 histone. In this study, we show that Transglutaminase 2 protein (TG2) is necessary to induce necroptosis pathway allowing the expression ofRipk3gene. Indeed, cells lacking TG2 show a strong downregulation ofRipk3gene and are resistant to necroptotic stimuli. TG2 is known to promote the serotonylation of H3K4me3 histone (H3K4me3Q5ser) regulating in this way the target gene expression. Interestingly, we find that TG2 interacts with both histones H3K4me3 and H3K4me3Q5ser and these post-translational modifications are associated with theRipk3promoter only in presence of TG2. In addition, the absence of the H3K4me3Q5ser, in cells lacking TG2, is correlated withRipk3gene methylation. Altogether, these results indicate that RIPK3 expression requires TG2 mediated serotonylation of H3K4me3 to preventRipk3promoter methylation, thus favouring its expression and necroptosis induction.

HIGHLIGHTS

- Transglutaminase 2 protein (TG2) is necessary to induce necroptosis.

- Cells lacking TG2 show a strong downregulation ofRipk3gene.

- TG2 allows Ripk3 gene expression by promoting the serotonylation on H3K4me3 histone.

SYNOPSIS

- TG2 serotonylates histone H3K4me3, associated toRipk3promoter, favoring its expression.

- TG2 dependent serotonylation of histone H3K4me3 prevents DNA methylation.

- TG2 favours the expression of Ripk3 making cells susceptible to necroptosis.

- In the absence of TG2, neither serotonylation nor methylation occur on histone H3, associated to Ripk3 promoter.

- In the absence of TG2, Ripk3 promoter is methylated, thus blocking the activation of necroptosis.
SNAI2 cooperates with MEK1/2 and HDACs to suppress BIM- and BMF-dependent apoptosis inTERTpromoter mutant cancers
Authors: Tandon Amol , Stern Josh
Published: October 2024

Cancers withTERTpromoter mutations (TPM) display elevated RAS pathway signaling and mesenchymal traits, and associate with lower patient survival rates. We examined whether RAS pathway signaling in TPM cancers cooperates with mesenchymal features to drive resistance to apoptosis. We observed that RAS pathway signaling in TPM cancers inhibited apoptosis by downregulating the pro-apoptotic protein BIM. By using inhibitors of MEK1/2 kinases, we rescued the ability of TPM cancer cells to undergo apoptosis, which may have implications for targeted therapies. To further capitalize on this rescue, we explored combination treatments to drive apoptotic cell death. Treatment with the pan-BCL2 inhibitor, navitoclax (NX), in combination with MEK inhibition, significantly increased apoptosis, indicating that these cells are capable of undergoing intrinsic apoptosis, with BIM likely playing a critical role. Further, we found that transcriptional reprogramming of the mesenchymal state of TPM cancers using histone deacetylase inhibitors (HDACi) resulted in a synergistic increase in apoptosis, contingent upon BIM de-repression. Notably, the cause of this apoptosis appeared to be independent of DNA damage. The suppression of the mesenchymal transcription factor SNAI2, which has known roles in recruiting HDACs to silence gene expression, amplified apoptosis. Mechanistically, knockdown of SNAI2 impaired the cellular DNA repair leading to elevated basal levels of phosphorylated H2AX. Our findings show that TPM cancers exhibit specific small molecule vulnerabilities, driven by the convergence of RAS-MEK signaling and impaired HDAC regulation dependent on pro-apoptotic BH3-only proteins. Based on our findings, we propose that stratifying cancers based on TPM may identify a subset of tumors that are responsive to innovative combinations of inhibitors targeting these axes.
Systemic effects of cystic fibrosis transmembrane conductance regulator (CFTR) modulators on the blood proteome
Authors: Fentker Kerstin , Kirchner Marieluise , Ziehm Matthias , Niquet Sylvia , Popp Oliver , Duerr Julia , Schaupp Laura , Roehmel Jobst , Thee Stephanie , Hämmerling Susanne , Sommerburg Olaf , Stahl Mirjam , Graeber Simon Y. , Mall Marcus A. , Mertins Philipp
Published: October 2024

Cystic fibrosis (CF), resulting from a dysfunction in the cystic fibrosis transmembrane conductance regulator (CFTR), affects multiple organs through mucus obstruction and differences in secretion. The CFTR modulator drug combination elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA, ETI) has markedly improved clinical symptoms, but its broader molecular and systemic effects remain to be fully elucidated.

We employed mass spectrometry-based proteomics to compare the blood proteomes of CF patients treated with the earlier, less effective lumacaftor/ivacaftor (LUM/IVA) combination against those receiving the more potent ELX/TEZ/IVA therapy. Our analysis revealed both specific and common pharmacodynamic signatures associated with inflammation and metabolic processes under each treatment regimen. Notably, ELX/TEZ/IVA therapy exhibited more consistent alterations across patients that were directed towards profiles observed in healthy individuals.

Furthermore, by comparing sputum and blood proteomes of ELX/TEZ/IVA treated patients we identified counter-directional changes in the pulmonary surfactant-associated protein B, SFTPB, a potential biomarker of lung tissue repair, which also correlated with lung function improvements.

This study provides a comprehensive resource that enhances our understanding of CFTR modulator-driven proteome alterations, offering insights to both systemic and local protein regulation in CF. Our findings indicate that ELX/TEZ/IVA promotes broader systemic health improvements, providing critical insights that could shape future therapeutic strategies in CF.
Multiplexed phosphoproteomics of low cell numbers using SPARCE
Authors: Gaizley Emily J. , Chen Xiuyuan , Bhamra Amandeep , Surinova Silvia
Published: October 2024

Understanding cellular diversity and disease mechanisms requires global analysis of proteins and their modifications. While next-generation sequencing has advanced our understanding of cellular heterogeneity, it fails to capture downstream signalling networks. Ultrasensitive mass spectrometry-based proteomics enables unbiased protein-level analysis of low cell numbers, down to single cells. However, phosphoproteomics remains limited to high-input samples due to sample losses and poor reaction efficiencies associated with processing low cell numbers. Isobaric stable isotope labelling is a promising approach for reproducible and accurate quantification of low abundant phosphopeptides. Here, we introduce SPARCE (StreamlinedPhosphoproteomicAnalysis ofRareCElls) for multiplexed phosphoproteomic analysis of low cell numbers. SPARCE integrates cell isolation, water-based lysis, on-tip TMT labelling, and phosphopeptide enrichment. SPARCE outperforms traditional methods by enhancing labelling efficiency and phosphoproteome coverage. To demonstrate the utility of SPARCE, we analysed four patient-derived glioblastoma stem cell lines, reliably quantifying phosphosite changes from 1,000 FACS-sorted cells. This workflow expands the possibilities for signalling analysis of rare cell populations.
Monitoring lysosomal catabolism: a sensitive probe for assessing targeted lysosomal degradation of extracellular proteins
Authors: Holly Ryan W. , Hu Yi-Zhen , Valsan Vaishnavi Beena , Kougentakis Christos , Petronikolou Nektaria , Chen Tao , Li Diana , Chen Aimei , Rank Steve , Doran Kyle H. , Turtle Eric , Langsdorf Christopher , Shurtleff Matthew J.
Published: October 2024

Extracellular targeted protein degradation (eTPD) is an emerging therapeutic field. The Lysosome targeting chimera (LYTAC) is a therapeutic modality that promotes degradation of extracellular drivers of disease in the lysosome. While widely available pH-sensitive probes may report on lysosome delivery, these probes do not necessarily report on the enzymatically active functional state of the lysosome. We report the development and application of a sensitive fluorescent probe, LysoLight Deep Red, to monitor catabolism of internalized proteins in the lysosome based on cleavage by cathepsin proteases. We demonstrate the application of Lysolight Deep Red to monitor the catabolic fate of therapeutic monoclonal antibodies, ASGPR-targeted LYTAC therapeutics and LYTAC targets in immortalized cell lines and in primary human hepatocytes.
Nirmatrelvir-Resistant Mutations in SARS-CoV-2 Mpro Enhance Host Immune Evasion via Cleavage of NF-κB Essential Modulator
Authors: Thomas Merrilee , Hughes Thom
Published: October 2024

Nirmatrelvir is a SARS-CoV-2 Mpro inhibitor in Paxlovid. Patients treated with it often produce mutant viruses in which the Mpro resists Nirmatrelvir inhibition. A common interpretation is that the mutations allow the virus to escape inhibition, but here we report that these mutations enable the protease to more effectively cleave the host protein NF-kappa-B essential modulator (NEMO), which weakens the immune response, improves viral replication, and may contribute to long COVID.
An efflux pump family distributed across plant commensal bacteria conditions host- and organ-specific detoxification of a host-specific glucosinolate
Authors: Russ Dor , Fitzpatrick Connor R. , Saha Chinmay , Law Theresa F. , Jones Corbin D. , Kliebenstein Daniel J. , Dangl Jeffery L.
Published: October 2024

In nature, plants recruit a diverse microbial community, the plant microbiome, that is distinct from the surrounding soil community1–4. To understand the forces that shape the plant microbiome we need to characterize the microbial traits that contribute to plant colonization. We used barcoded mutant libraries to identify bacterial genes that contribute to the colonization of a monocot and a eudicot host5–7. We show that plant colonization is influenced by dozens of genes. While some of these colonization genes were shared between the two host plant species, most were highly specific, benefiting the colonization of a single host and organ. We characterized an efflux pump that specifically contributes to Arabidopsis shoot colonization. This efflux pump is prevalent across Pseudomonadota genomes, yet benefits the bacterial association with only a small subset ofArabidopsis thalianaaccessions. Leveraging genomic diversity withinArabidopsis thaliana, we confirmed that specific glucosinolate breakdown products are detoxified by this family of efflux pumps. The broad prevalence of this efflux pump family suggests that its members contribute to protection of commensal bacteria from collateral damage of plant glucosinolate-based defense responses to herbivores and necrotrophic pathogens.
Tissue-Like Multicellular Development Triggered by Mechanical Compression in Archaea
Authors: Rados Theopi , Leland Olivia S. , Escudeiro Pedro , Mallon John , Andre Katherine , Caspy Ido , von Kügelgen Andriko , Stolovicki Elad , Nguyen Sinead , Patop Inés Lucía , Rangel Thiberio , Kadener Sebastian , Renner Lars D. , Thiel Vera , Soen Yoav , Bharat Tanmay A.M. , Alva Vikram , Bisson Alex
Published: October 2024

The advent of clonal multicellularity is a critical evolutionary milestone, seen often in eukaryotes, rarely in bacteria, and only once observed in archaea. We show that uniaxial compression induces clonal multicellularity in haloarchaea, forming tissue-like structures. These archaeal tissues are mechanically and molecularly distinct from their unicellular lifestyle, mimicking several eukaryotic features. Archaeal tissues undergo a multinucleate stage followed by tubulin-independent cellularization, orchestrated by active membrane tension at a critical cell size. After cellularization, tissue junction elasticity become akin to animal tissues and give rise to two cell types—radial peribasal and central apicobasal cells— with distinct actin and protein glycosylation polarity patterns. Our findings highlight the potential convergent evolution of a biophysical mechanism in the emergence of multicellular systems across domains of life.
Shock wave propagation in a real gas with or without gravitational field in the presence of magnetic field and monochromatic radiation via group invariance method
Authors: Nath G. , Upadhyay P.
Published: October 2024

Purpose

This article aims to find the similarity solutions for the one-dimensional motion of spherical symmetric shock wave in non-ideal gas influenced by the azimuthal magnetic field and monochromatic radiation in the presence or absence of gravitational field. This paper also aims to study the effects of physical parameters on the strength of shock wave, and on the flow variables in the flow-field region behind the shock front.

Design/methodology/approach

The Roche model is used to describe the gravitational field effects due to a massive nucleus at the point of symmetry. To derive the similarity solutions, the Lie group symmetry method has been used. Also, the numerical solutions to the present problem are obtained by using Rung–Kutta method of the fourth order with the use of Mathematica software. The effects of variation in the parameter of non-idealness of the gas, the gravitation parameter, the strength of the ambient magnetic field and the adiabatic index of the gas on the shock wave, and on the flow variables is discussed. A comparative study between with and without gravitational field is also, made.

Findings

For different choices of the arbitrary constants that appeared in the solution of infinitesimal generators, we have obtained seven distinct cases of similarity solutions. In the absence of the gravitational field, the similarity solution exists to the power and exponential law shock paths, but in the presence of gravitational field, the similarity solution exists to the power law shock path case only. In the absence of gravitational field, the shock strength is enhanced in the exponential law shock path case in comparison to the power law shock path case. It is found that the shock wave decays with an increase in the value of the adiabatic exponent, the strength of magnetic field, non-idealness of the gas or gravitational parameter.

Research limitations/implications

The consideration of medium under the influence of gravitational field due to a heavy nucleus at the center and presence of magnetic field decrease the shock strength. This result may be helpful in designing space vehicle and jet engine.

Practical implications

The result of the present study may be used in the analysis of data from the measurements by space craft in the solar wind and in neighborhood of the Earth’s magnetosphere.

Social implications

The obtained results may be used for mankind.

Originality/value

The study of spherical shock wave propagation influenced by monochromatic radiation and azimuthal magnetic field in a non-ideal gas with or without gravitational field has yet to be discussed by any authors by using the Lie group symmetry method. In this article, we have discussed all possible cases of similarity solutions using the Lie group symmetry method, which is not studied by anyone as known to us.
Adoption challenges of building information modelling (BIM) and off-site construction (OSC) in healthcare construction: are they fellow sufferers?
Authors: Tan Tan , Mills Grant , Ma Xiaolin , Papadonikolaki Eleni
Published: October 2024

Purpose

Off-Site Construction (OSC) has received much government and public attention during and after COVID. Building Information Modelling (BIM) is an initiative discussed widely to promote OSC implementation. Although many policy promotions have been published, there are many challenges to implementing BIM and OSC in real life and questions of whether they really offer value to healthcare design professionals. This research aims to investigate BIM and OSC to understand their commonalities and differences of challenges by collecting empirical evidence from China’s healthcare construction.

Design/methodology/approach

This exploratory research adopted a mixed method with a questionnaire survey and interviews. A total of 261 questionnaires were received (with 183 valid), followed by 31 semi-structured interviews.

Findings

This research reveals that although both OSC and BIM face similar adoption challenges and suspicious attitudes in real-life projects, their challenges’ connotations and reasons are different. OSC faces scepticism for its customisation costs and technical constraints, while BIM is seen as limited in utility and complex to integrate. Highlighting these as socio-technical challenges, the research advocates for an integrated framework to effectively implement OSC and BIM, addressing both technical and collaborative needs in healthcare construction.

Originality/value

This research examines OSC and BIM within the context of healthcare construction, a focus that is relatively underexplored. The research provides a juxtaposition of the perceived and practical challenges of adopting these technologies, revealing a gap between the industry’s expectations and the current capabilities of OSC and BIM, thereby contributing to the development of modern methods of design in healthcare.
Revolutionising construction safety: benefits of harnessing artificial intelligence tools for dynamic monitoring of safety compliance on construction projects in Nigeria
Authors: Adamu Ibrahim Inyass , Okanlawon Taofeek Tunde , Oyewobi Luqman Oyekunle , Shittu Abdullateef Adewale , Jimoh Richard Ajayi
Published: October 2024

Purpose

This paper evaluates the benefits of harnessing artificial intelligence (AI) tools for safety compliance on construction projects in Nigeria.

Design/methodology/approach

This study employed a specialised approach by combining qualitative and quantitative approach. The study carried out a brief systematic literature review (SLR) to identify the variables of the study. These variables were prepared in a questionnaire which was distributed among professionals within the Nigerian construction sector using purposive sampling. A total of 140 questionnaires were retrieved. The collected data were analysed using Relative Importance Index (RII), Ginni’s Mean (GM) and exploratory factor analysis (EFA).

Findings

The analysis revealed that all the identified benefits hold considerable importance, with an average RII of 0.86, with real-time monitoring as the most prominent advantage. However, using the GM which was 0.861, the study identified “mitigation of hazards on worksites” as the stationary benefit of AI in safety compliance.

Research limitations/implications

The study was conducted exclusively within Nigeria’s Federal Capital Territory, using a cross-sectional survey approach.

Practical implications

The results will be valuable for professionals and practitioners in the Nigerian construction sector, as they will acquire insights into the potential advantages of utilising AI tools for monitoring of safety compliance on construction projects.

Originality/value

The study adopted a robust approach by identifying the stationary benefit using the GM in combination with RII and EFA.
Investigating the lurking mechanism of SNS users: a comprehensive examination of context-specific cues and role stresses
Authors: Liu Xiaodan , Su Chao , Yin Jin
Published: October 2024

Purpose

Social networking services (SNS) empower users with a robust capability to connect with others and manage their social relationships. However, as the size of users’ social networks increases, coupled with the inherent boundary-spanning technical features of SNS, users are faced with unprecedented role stresses. This, in turn, leads to maladaptive lurking decisions. This study delves into the mechanism of this technology-induced decision-making process among SNS users.

Design/methodology/approach

Survey data were collected from 491 Chinese WeChat Moment users. The model and hypotheses testing were conducted using SmartPLS 4.0.

Findings

Our findings indicate that both social network size and boundary spanning have a positive influence on role conflict and role overload. Both role conflict and role overload significantly contribute to SNS fatigue, which further intensifies users’ lurking intention. Furthermore, SNS fatigue fully mediated the relationship between role conflict and lurking intention, and partially mediated the relationship between role overload and lurking intention.

Originality/value

Our study offers a fresh viewpoint for comprehending lurking behaviors on SNS, furnishing practical insights for platform providers. Additionally, it paves the way for future research into the deeper mechanisms driving SNS lurking behaviors, by providing a novel construct (i.e. boundary spanning) to distinguish and measure the unique social environment of SNS.
Knowledge sharing among academics in higher education: integrating positive and negative facets of organizational climate
Authors: Fan Zhenyu , Beh Loo-See
Published: October 2024

Purpose

Knowledge sharing is pivotal for the professional development among academics in higher education. However, little research has focused on understanding both the positive and negative facets of organizational climate in relation to knowledge sharing among academics. Based on the theory of planned behavior, this study aims to examine the impact of four facets of organizational climate, i.e. affiliation, trust, competition and individualism, on academics’ subjective norms and intentions regarding knowledge sharing.

Design/methodology/approach

Survey data were collected from 532 university faculty staff in China and analyzed using partial least squares structural equation modeling.

Findings

Results indicated that affiliation and trust had positive effects on subjective norms regarding knowledge sharing, whereas competition and individualism had negative effects on subjective norms. Furthermore, subjective norms were found to significantly enhance academics’ intentions to share knowledge.

Practical implications

Practical implications are provided on how to cultivate a supportive organizational climate to foster knowledge sharing among faculty staff for enhanced professional capital and competitiveness.

Originality/value

The study contributes to the literature by integrating both the positive and negative facets of organizational climate and highlighting the hindering effects of competition and individualism on knowledge sharing, which have not been fully investigated in the existing literature.
Explaining training and adjustment diversity in multinational enterprises: literal and figurative interpretations
Authors: Mandrinos Symeon , Liew Sat Lin Constance , Ilma binti Salleh Nurul
Published: October 2024

Purpose

This study emphasises the importance of both literal and figurative interpretations in explaining training and adjustment (cross-cultural) diversity in a multinational enterprise (MNE) context.

Design/methodology/approach

The study employs structural equation models applied to employees relocated to a Malaysian subsidiary. It emphasises the importance of distinguishing between measurement, analysis and interpretation. This distinction highlights the need to not only directly quantify variables but also indirectly interpret their relationships to address diversity.

Findings

The findings underscore the significance of figurative interpretation in understanding diversity, particularly at the micro level. Literal interpretation focuses on direct analysis, while figurative interpretation involves an indirect analysis where diversity may not be immediately evident. The study suggests that considering both macro and micro levels is essential in understanding training and adjustment diversity.

Originality/value

This study offers a novel perspective by incorporating both literal and figurative interpretations to deepen the understanding of diversity in international business contexts. It uniquely positions itself by distinguishing between the direct quantification of variables and the indirect interpretation of their relationships. This dual approach enables a more comprehensive understanding of how training, adjustment, compliance with standards and commitment to expectations interact within MNEs. By advocating for figurative interpretation, the study encourages a more holistic analysis that extends beyond surface-level metrics, providing valuable insights for future research. It also paves the way for practitioners to develop strategies that not only address diversity at both macro and micro levels but also foster adaptability within culturally diverse work environments.
Meta‐analysis reveals low language capacity in childhood is associated with mental health problems in adulthood
Authors: Lim Shelby W. Y. , Lum Jarrad A. G.
Published: October 2024

Background

Children and adolescents with language problems have poorer mental health compared with their non‐language impaired peers. Less is known about mental health in adults with a history of language problems. This paper presents a systematic review and meta‐analysis that addresses this gap in the literature. Specifically, it summarises the results from studies examining anxiety and depression in adults (aged 18 years and over) who were identified with language impairments or problems earlier in development.

Methods & Procedures

Five electronic databases (PsycINFO, ERIC, CINAHL, EMBASE and PubMed) were searched for studies comparing anxiety and/or depression in a sample of adults with and without a history of language problems. Nine studies were found that met the inclusion criteria. From each, an odds ratio (OR) was computed measuring the relationship between childhood language problems and anxiety or depression in adulthood. The OR was computed so values > 1 which indicated anxiety/depression were associated with a history of language problems. ORs were averaged using multilevel random effects meta‐analysis.

Outcomes & Results

Averaging the study's findings across both anxiety and depression outcomes, we found that a history of childhood language problems was associated with poorer mental health in adulthood (OR = 1.79, p = 0.004). The association for anxiety was also significant (OR = 1.80, p = 0.012) and close to statistical significance for depression (OR = 1.60, p = 0.054).

Conclusions & Implications

This review reveals that adults with a history of language problems are more likely to experience poorer mental health outcomes compared with controls. These findings demonstrate childhood language problems affect not only communication but also mental health and well‐being in the long term.

WHAT THIS PAPER ADDS

What is already known on the subject

Prior research examining mental health in children and adolescents with language problems reveals a twofold increased risk of internalising problems, including anxiety and depression. However, little is known about mental health outcomes in adults with a history of language problems.

What this paper adds to the existing knowledge

The main finding was that childhood language problems are associated with increased risk of anxiety and depression in adulthood.

What are the practical and clinical implications of this work?

First, the study demonstrates childhood language problems increase the risk of poor mental health in adulthood. Second, in adult mental health settings there is a need to screen for language problems and, where applicable, adjust interventions to accommodate communicative needs for patients/clients. Solving these issues requires integration and recognition of the importance of speech–language therapy in the adult mental health system.
U.S. against the world: Authoritarianism among American public servants
Authors: Bednarczuk Michael E.
Published: October 2024

What is the prevalence of authoritarianism among public servants in the United States, and what are its resulting consequences? Several underlying psychological traits are associated with both authoritarianism and a desire to work in the public sector, such as an aversion to ambiguity and a preference for order and security. Scholarship also suggests that those with high authoritarian attributes may see the world through an ‘us versus them’ prism; in this case, the ‘them’ may be represented by other countries. Therefore, it is hypothesised that those with higher authoritarian attributes are more likely to work in the public sector and that public servants with higher authoritarian attributes are more likely to be sensitive to potential threats to the country. Using six surveys that cover a 20‐year period from the American National Elections Study, both hypotheses are supported. Authoritarian attributes  are associated with an increased likelihood of government employment. Additionally, authoritarian public servants tend to support government wiretapping and express greater concern about terrorism. The presence of authoritarianism among public sector employees has implications for a range of governance issues, which makes it important to understand where and to what degree it is prevalent.

Points for practitioners

More attention should be devoted to the division and prevalence of authoritarian attributes within public servants .

Checks and oversight mechanisms should be implemented for public sector employees in sensitive areas to help counterbalance potential authoritarian impulses.

Organisational cultures that value openness, evidence‐based policymaking, and tolerance for dissenting viewpoints should be fostered as a counterweight to authoritarian preferences for conformity.
Genetic variation in bovine milk proteins: Implications for functional and nutritional properties
Authors: Kelly Liam M , O'Mahony James A , Tobin John T
Published: October 2024

The six major bovine milk proteins are encoded by highly polymorphic chromosomes. Genetic variation has become a topic of interest and controversy in recent years due to supposed adverse health effects, beginning with the A2 variant of β‐casein. The functional implications of genetic variants have been well characterised, specifically heat stability and coagulation (i.e. rennet and acid) properties of milk, which have found that the B variant of β‐casein, κ‐casein and β‐lactoglobulin are the most beneficial. Genetic variants of milk proteins provide considerable potential to create new dairy products to add value to milk.
Effect of administration sequence of induction agents on first‐attempt failure during emergency intubation: A Bayesian analysis of a prospective cohort
Authors: Catoire Pierre , Driver Brian , Prekker Matthew E. , Freund Yonathan
Published: October 2024

Background

Emergency tracheal intubation is associated with a risk of clinical adverse events, including the risk of first‐attempt failure. Induction agents usually include a sedative and a neuromuscular blocking agent (i.e., paralytic). Whether the order of administration (i.e., sedative vs. paralytic given first) is associated with first‐attempt failure or adverse events is unknown.

Methods

This study analyzed data from a single‐center prospective cohort collected from 2021 to 2024 at Hennepin County Medical Center, which included all patients undergoing orotracheal intubation in the emergency department. Patients with no detail on administration sequence order were excluded. A Bayesian logistic regression analysis was used to measure the effect of drug sequence order (sedative first vs. paralytic first). The primary outcome was first‐attempt failure. The key secondary outcome was peri‐intubation hypoxemia (SpO2 < 90%). We estimated the odds ratio (OR), 95% credible interval (CrI), and the probability that the OR was inferior to 1 (existence of an effect) and inferior to 0.9 (significant effect). Frequentist analysis and reanalysis with various priors were performed as sensitivity analyses.

Results

A total of 2216 patients were included for analysis. The most frequently used sedative and paralytic agents were etomidate (88.9%) and rocuronium (77.8%), respectively. The paralytic was given first to 56.6% of the patients. After adjustment for age, sex, body mass index, and sedative and paralytic agents, the OR for a paralytic‐first strategy for first‐attempt failure was 0.73 (95% CrI 0.46–1.02). The probability that the OR was less than 1 was estimated at 95.7% and less than 0.9 at 87.6%. There was a 33.5% and 8.0% probability that administering the paralytic first resulted in an OR < 1 and OR < 0.9 for the risk of hypoxemia, respectively. Sensitivity analyses were consistent with the main results.

Conclusions

In this Bayesian analysis a paralytic‐first drug sequence was associated with reduced first‐attempt failure during emergency tracheal intubation.
Association of circulating adipokines with metabolic measures among people with HIV: Moderating effects of alcohol use
Authors: Simon Liz , Lin Hui‐Yi , Poret Jonquil , Stouwe Curtis Vande , Ferguson Tekeda F. , Welsh David A. , Molina Patricia E.
Published: October 2024

Background

People with HIV (PWH) are at increased risk for cardiometabolic comorbidities. We have reported that lifetime alcohol use among people with HIV (PWH) is associated with increased risk for metabolic syndrome. Dysfunctional adipose tissue and altered circulating adipokines mediate metabolic dysregulation. The objective of this study was to determine the associations of circulating adipokine concentration with metabolic measures, and the moderating effects of lifetime and recent alcohol use in PWH.

Methods

This is a cross‐sectional analysis of data from 357 PWH at their baseline visit of the longitudinal New Orleans Alcohol and HIV (NOAH) study. The concentrations of four circulating adipokines (adiponectin, leptin, resistin, and fatty acid‐binding protein 4 [FABP4]) and their associations with five metabolic measures (triglycerides, cholesterol, Hemoglobin A1c, Homeostatic Model Assessment for Insulin Resistance, and metabolic syndrome) were examined.

Results

Higher circulating adiponectin was associated with increased odds of normal triglyceride, cholesterol, and Hemoglobin A1c levels. Increased leptin and FABP4 concentrations were associated with decreased odds of normal triglyceride and cholesterol levels. Increased leptin and FABP4 concentrations were associated with increased odds of insulin resistance and meeting criteria for metabolic syndrome. Increased circulating resistin concentration was associated with decreased odds of normal triglyceride levels and increased odds of meeting criteria for metabolic syndrome. Additionally, among PWH with increased lifetime alcohol use, higher adiponectin concentration was associated with decreased odds of meeting criteria for metabolic syndrome.

Conclusions

These data suggest the interplay between adiponectin, leptin, FABP4, and resistin may contribute to metabolic stability among PWH. Moreover, lifetime, but not recent, alcohol use moderates the relationship between adipokines and metabolic measures. These data highlight the relevance of functional adipose tissue mass and associated circulating adipokine levels in maintaining metabolic homeostasis, and its moderation by lifetime alcohol consumption.
Case of Successful Sympathetic Nerve Modulation by Targeted Heavy Ion Radiotherapy for Idiopathic Ventricular Tachycardia
Authors: Amino Mari , Wakatsuki Masaru , Mori Shinichiro , Shimokawa Takashi , Kabuki Shigeto , Kunieda Etsuo , Hashimoto Jun , Yamashita Takashi , Yagishita Atsuhiko , Ikari Yuji , Yoshioka Koichiro
Published: October 2024

Non‐invasive radioablation using stereotactic body radiation therapy with X‐ray has been proposed as a rescue treatment for refractory ventricular tachycardia (VT). However, there are concerns about the occurrence of late valvular or coronary disease. We treated VT originating from the aortic sinus cusp using the Bragg peak principle of a heavy ion beam, minimizing the dose to the aortic valve and coronary artery and providing an anti‐arrhythmic effect and cardiac function recovery due to improved sympathetic nerve heterogeneity. We present a method for targeting sympathetic nerve distribution using 123I‐metaiodobenzylguanidine scintigraphy.
Grading of diabetic retinopathy using a pre‐segmenting deep learning classification model: Validation of an automated algorithm
Authors: Similié Dyllan Edson , Andersen Jakob K. H. , Dinesen Sebastian , Savarimuthu Thiusius R. , Grauslund Jakob
Published: October 2024

Purpose

To validate the performance of autonomous diabetic retinopathy (DR) grading by comparing a human grader and a self‐developed deep‐learning (DL) algorithm with gold‐standard evaluation.

Methods

We included 500, 6‐field retinal images graded by an expert ophthalmologist (gold standard) according to the International Clinical Diabetic Retinopathy Disease Severity Scale as represented with DR levels 0–4 (97, 100, 100, 103, 100, respectively). Weighted kappa was calculated to measure the DR classification agreement for (1) a certified human grader without, and (2) with assistance from a DL algorithm and (3) the DL operating autonomously. Using any DR (level 0 vs. 1–4) as a cutoff, we calculated sensitivity, specificity, as well as positive and negative predictive values (PPV and NPV). Finally, we assessed lesion discrepancies between Model 3 and the gold standard.

Results

As compared to the gold standard, weighted kappa for Models 1–3 was 0.88, 0.89 and 0.72, sensitivities were 95%, 94% and 78% and specificities were 82%, 84% and 81%. Extrapolating to a real‐world DR prevalence of 23.8%, the PPV were 63%, 64% and 57% and the NPV were 98%, 98% and 92%. Discrepancies between the gold standard and Model 3 were mainly incorrect detection of artefacts (n = 49), missed microaneurysms (n = 26) and inconsistencies between the segmentation and classification (n = 51).

Conclusion

While the autonomous DL algorithm for DR classification only performed on par with a human grader for some measures in a high‐risk population, extrapolations to a real‐world population demonstrated an excellent 92% NPV, which could make it clinically feasible to use autonomously to identify non‐DR patients.
Reference values for cerebral and peripheral tissue oximetry in children: A clinical TD‐NIRS study
Authors: Calcaterra Valeria , Lacerenza Michele , Rossi Virginia , Zanelli Sara , Contini Davide , Amendola Caterina , Buttafava Mauro , Torricelli Alessandro , Zuccotti Gianvincenzo
Published: October 2024

Aim

Current non‐invasive near‐infrared spectroscopy (NIRS) tissue oximetry suffers from suboptimal reproducibility over probe repositioning, hindering clinical threshold establishment. Time Domain‐NIRS (TD‐NIRS) offers higher precision but lacks sufficient paediatric data, preventing effective clinical application. We aimed to establish reference ranges for cerebral and mid‐upper arm (MUA) tissue haemodynamics in paediatric subjects using TD‐NIRS and explore correlations with auxological variables.

Methods

TD‐NIRS measurements were conducted acquiring data from cerebral and MUA regions with the NIRSBOX tissue oximeter. Morphological and clinically relevant information were collected to explore potential correlations with TD‐NIRS derived parameters.

Results

TD‐NIRS assessment was applied in 350 children (8.4 ± 5.0 years). Precision of TD‐NIRS was demonstrated with standard deviations of 0.9% (StO2) and 4.2 μM (tHb) for frontotemporal cerebral cortex, and 0.8% (StO2) and 3.7 μM (tHb) for MUA. No user dependency was observed. The trends of values for cerebral and peripheral regions vary differently according to age and auxological parameters.

Conclusion

This study reports resting‐state optical and haemodynamic values for a healthy paediatric population, providing a foundation for future investigations into clinically relevant deviations in these parameters. Furthermore, correlations with anthropometric and demographic values provide valuable insights for a deeper understanding of tissue haemodynamic evolution in childhood.
The Shifting and Permeable Boundaries of Auditing: Evidence from Early Australian Examination Papers
Authors: Potter Brad
Published: October 2024

The Colin Ferguson Oration is the address given to attendees at the annual Australia Accounting Hall of Fame dinner and presentation evening. It is an invited oration, whereby an eminent modern‐day leader addresses the audience on matters at the intersection of business, government and the academe as they relate to the rich history, the current state and/or the future direction of the accounting profession. The oration is named in honour of Professor Colin Ferguson (1949–2014). Colin was the key figure driving the inception of the Australian Accounting Hall of Fame. In a decorated academic career, he worked tirelessly for many years and with great distinction at the intersection of accounting thought and practice encompassing auditing, forensic accounting and accounting information systems, so it was only fitting that this oration is named in his honour. This year's oration was delivered by Brad Potter, an Associate Professor of Accounting and a Director of the Centre for Accounting and Industry Partnerships at the University of Melbourne. Brad's research and consulting experience encompasses financial accounting and disclosure for both private sector and public sector entities. In particular, he has successfully managed and coordinated research projects involving the Australian Accounting Standards Board, National Water Commission, CPA Australia, the Institute of Chartered Accountants, Australia, Royal Botanic Gardens and the Institute of Public Accountants (IPA). This year's oration uses a unique dataset to gain insights into the development of the auditing profession, a topic of interest to academe, practitioners and standard‐setters, and one that is eminently suitable for publication in the Australian Accounting Review.
The influence of valence and relationship on children's verification of gossip
Authors: Wan Zhehua , Wang Binjie , Harris Paul L. , Tang Yulong
Published: October 2024

Given that children do not always trust gossip, do they spontaneously check what they are told? We provided 5‐ (N = 32) and 6‐year olds (N = 32) with gossip concerning characters in a cartoon they were watching, and examined whether they verified the gossip by actively re‐watching the relevant episodes. Six‐year olds were more likely to verify gossip than 5‐year olds. When gossip targeted their favourite characters, children were more likely to verify negative when compared with positive gossip. However, when gossip targeted children's disliked characters, they showed no such valence bias. These results indicate that children's verification of gossip increases with age, and they evaluate claims selectively.
Results of Platelet‐Rich Fibrin Application in Pharyngeal Reconstruction After a Total Laryngectomy
Authors: Başkadem Yilmazer Ayça , Aksungur Elif , Çelik Cem , Bayram Avni Akin , Turgut Hüseyin , Dinç Mehmet Emre , Göker Ayşe Enise , Uyar Yavuz
Published: October 2024

Introduction

Pharyngocutaneous fistula (PCF) is one of the most challenging complications observed after a total laryngectomy. Since the biochemical components of platelet‐rich fibrin (PRF) have well‐known synergistic effects on the healing processes, this study aimed to demonstrate the contribution of PRF application to pharyngeal healing in patients undergoing a total laryngectomy for laryngeal cancer.

Methods

The study compared patients who underwent a total laryngectomy due to laryngeal squamous cell carcinoma and had a PRF membrane placed during the pharyngoesophageal closure with those who did not. There were two groups: PRF‐positive and PRF‐negative. In the PRF‐positive group, after the completion of the total laryngectomy and moving on to the pharyngoesophageal closure stage, along the suture line, PRF material is laid in two pieces in a T‐shape and secured with several sutures. No PRF application was done in the PRF‐negative group. Pharyngeal healing steps (nasogastric feeding, oral feeding, development of a fistula), haemoglobin and albumin values, tumour involvement areas, time to oral intake and length of hospital stay were recorded for all patients.

Results

This study reviewed the records of 33 patients who underwent pharyngoesophageal closure with PRF application after a total laryngectomy (PRF‐positive group) and 35 patients without PRF application (PRF‐negative group). When comparing patients in terms of developing a PCF, 6% (n = 2) of patients in the PRF‐positive group and 25.7% (n = 9) in the PRF‐negative group developed a fistula. This ratio was significantly higher in the PRF‐negative group (p = 0.027).

Conclusion

The application of PRF in pharyngoesophageal reconstruction after a total laryngectomy may strengthen wound healing and reduce the risk of PCF development.

Trial Registration

This study is a retrospective designed study; therefore, there is no clinical trial registration