bluuebunny/crossref_metadata_2025 huggingface dataset:
ILSM: A package for analyzing the interconnection structure of tripartite interaction networks
Authors: Sun Weicheng , Zhao Yangyang , Yan Chuan
Published: November 2024

In natural or human-disturbed ecosystems, ecological networks often comprise multiple interaction types, which have been often represented by multipartite ecological networks. One important aspect of their network architecture is how different interaction types or subnetworks are interconnected by shared species, here defined as the interconnection structure. Previous studies have proposed various indices of shared species to characterize macro-scale interconnection patterns and micro-scale centrality, but the meso-scale interconnection structures (here defined as interconnection motifs) remain largely unexplored. Furthermore, there is no package available in the R programming language for conducting analyses of various interconnection structures.

Within a tripartite network with two interaction subnetworks, we define the forms of interconnection motifs and unique roles within these motifs. Then we introduce the R package ILSM for analyzing interconnection patterns, interconnection centrality, and interconnection motif. Specifically, we derive mathematical expressions for the frequencies of interconnection motifs and species roles within motifs.

We describe the main functions in the package and demonstrate their uses with an example pollinator-plant-herbivore network.

ILSM will help ecologists understand how different types of interactions are interconnected together by shared species using interconnection pattern, centrality and motif.
Vascular mural cells protect the adult brain from haemorrhage but do not control the blood-brain barrier in developing zebrafish
Authors: Baltaci Oguzhan F , Usseglio Gaudi Andrea , Dudczig Stefanie , Wang Weili , Rondon-Galeano Maria Cristina , Lim Ye-Wheen , Rae James , Lagendijk Anne , Parton Robert G , Farley Alison , Hogan Benjamin M
Published: November 2024

The blood-brain barrier (BBB) protects the brain from circulating metabolites and plays central roles in neurological diseases. Endothelial cells (ECs) of the BBB are enwrapped by mural cells including pericytes and vascular smooth muscle cells (vSMCs) that regulate angiogenesis, vessel stability and barrier function. To explore mural cell control of the BBB, we investigated neurovascular phenotypes in zebrafishpdgfrbmutants that lack brain pericytes and vSMCs. As expected, mutants showed an altered cerebrovascular network with mis-patterned capillaries. Unexpectedly, mutants displayed no BBB leakage from larval through to young adult stages. This demonstrates that pericytes and vSMCs do not control BBB function in young zebrafish. Instead, we observed adult BBB disruption occurring at "hotspot" focal haemorrhages at major vessel aneurysms. ECs at leakage hotspots showed induction of caveolae on abluminal surfaces and major structural defects including basement membrane thickening and disruption. Our work suggests that capillary pericytes regulate cerebrovascular patterning in development and vSMCs of major arteries protect from haemorrhage and BBB breakdown in older zebrafish. The fact that young zebrafish can have a conserved BBB with intact barrier function in the absence of mural cells, warrants renewed interrogation of the paradigm of mural cell control of the BBB.
An auxin-inducible degron system for conditional mutation in the fungal meningitis pathogenCryptococcus neoformans
Authors: Huang Manning Y. , Nalley Matt J. , Hecht Patrick , Madhani Hiten D.
Published: November 2024

Cryptococcus neoformansis the top-ranked W.H.O. fungal priority pathogen, but tools for generating conditional mutations are limited. Auxin-inducible degron systems permit rapid and effective cellular depletion of a tagged protein of interest upon adding a small molecule. These tools are invaluable, particularly for studying essential genes, which may play important roles in pathogen biology. AID2 is one such system that improves on previous strategies. This system achieves greater sensitivity and specificity using a “bumped” auxin, 5-Ph-IAA, alongside an OsTIR1(F74G) “hole” mutant. We adapted the AID2 system forC. neoformansby codon optimizing OsTIR1(F74G) and tested its use in multiple scenarios. We demonstrate that theC. neoformansoptimized AID2 system enables effective degradation of proteins, including essential proteins, and can be used to discriminate essential from non-essential genes. This tool enables the study of unexplored parts of theC. neoformansgenome.
CD73 restrains mutant β-catenin oncogenic activity in endometrial carcinomas
Authors: Hirsch Rebecca M. , Premsankar Sunthoshini , Kurnit Katherine C. , Chiou Lilly F. , Rabjohns Emily M. , Lee Hannah N. , Broaddus Russell R. , Vaziri Cyrus , Bowser Jessica L.
Published: November 2024

Missense mutations in exon 3 ofCTNNB1, the gene encoding β-catenin, are associated with poor outcomes in endometrial carcinomas (EC). Clinically,CTNNB1mutation status has been difficult to use as a predictive biomarker as β-catenin oncogenic activity is modified by other factors, and these determinants are unknown. Here we reveal that CD73 restrains the oncogenic activity of exon 3 β-catenin mutants, and its loss associates with recurrence. Using 7 patient-specific mutants, with genetic deletion or ectopic expression of CD73, we show that CD73 loss increases β-catenin-TCF/LEF transcriptional activity. In cells lacking CD73, membrane levels of mutant β-catenin decreased which corresponded with increased levels of nuclear and chromatin-bound mutant β-catenin. These results suggest CD73 sequesters mutant β-catenin to the membrane to limit its oncogenic activity. Adenosine A1 receptor deletion phenocopied increased β-catenin-TCF/LEF activity seen withNT5Edeletion, suggesting that the effect of CD73 loss on mutant β-catenin is mediated via attenuation of adenosine receptor signaling. RNA-seq analyses revealed thatNT5Edeletion alone drives pro-tumor Wnt/β-catenin gene expression and, with CD73 loss, β-catenin mutants dysregulate zinc-finger and non-coding RNA gene expression. We identify CD73 as a novel regulator of oncogenic β-catenin and help explain variability in patient outcomes inCTNNB1mutant EC.Graphical Abstract
Behavioral risk models explain locomotor and balance changes when walking at virtual heights
Authors: Seddighi Nooshin , Woo Nicholas J. , Montoya Jaylie , Kreter Nicholas , Clark Mindie , Williams A. Mark , Raffegeau Tiphanie E. , Fino Peter C.
Published: November 2024

Walking in daily life requires humans to adapt to environments that can influence one’s fear of falling and anxiety about a potential fall. In such environments, individuals may adopt compensatory locomotor and balance changes to maintain a constant expected risk function equal to the product of the probability of some event (e.g., a fall) and the cost of that event (e.g., injury or death). Here, we tested whether locomotor behaviors broadly align with this risk model in two experiments with height-related threats in immersive virtual reality. In Experiment 1, we examined how individuals change their locomotor trajectory while walking along a straight high-elevation walkway. In Experiment 2, we examined how individuals change trajectory and balance control during curved walking where the location of high elevation threat varied. Participants adopted two behaviors that decreased their probability of falling off the edge and aligned with the risk-based model: participants altered their proximity to perceived threats that pose high costs (e.g., a high-elevation ledge), and decreased mediolateral center of mass velocity when that was not possible. Taken together, our results suggest that individuals alter locomotor behavior to change the probability of falling based on the perceived cost of that fall.
Modeling gene interactions in polygenic prediction via geometric deep learning
Authors: Li Han , Zeng Jianyang , Snyder Michael P. , Zhang Sai
Published: November 2024

Polygenic risk score (PRS) is a widely used approach for predicting individuals’ genetic risk of complex diseases, playing a pivotal role in advancing precision medicine. Traditional PRS methods, predominantly following a linear structure, often fall short in capturing the intricate relationships between genotype and phenotype. In this study, we present PRS-Net, an interpretable geometric deep learning–based framework that effectively models the nonlinearity of biological systems for enhanced disease prediction and biological discovery. PRS-Net begins by deconvoluting the genome-wide PRS at the single-gene resolution and then explicitly encapsulates gene–gene interactions leveraging a graph neural network (GNN) for genetic risk prediction, enabling a systematic characterization of molecular interplay underpinning diseases. An attentive readout module is introduced to facilitate model interpretation. Extensive tests across multiple complex traits and diseases demonstrate the superior prediction performance of PRS-Net compared with a wide range of conventional PRS methods. The interpretability of PRS-Net further enhances the identification of disease-relevant genes and gene programs. PRS-Net provides a potent tool for concurrent genetic risk prediction and biological discovery for complex diseases.
Uncovering measurement-induced entanglement via directional adaptive dynamics and incomplete information
Authors: Wang Yu-Xin , Seif Alireza , Clerk Aashish A.
Published: November 2024

The rich entanglement dynamics and transitions exhibited by monitored quantum systems typically only exist in the conditional state, making observation extremely difficult. In this Letter, we construct a general recipe for mimicking the conditional entanglement dynamics of a monitored system in a corresponding measurement-free dissipative system involving directional interactions between the original system and a set of auxiliary register modes. This mirror setup autonomously implements a measurement-feedforward dynamics that effectively retains a coarse-grained measurement record. We illustrate our ideas in a bosonic system featuring a competition between entangling measurements and local unitary dynamics, and also discuss extensions to qubit systems and truly many-body systems.

Published by the American Physical Society
2024
Measuring the molecular Migdal effect with neutron scattering on diatomic gases
Authors: Kahn Yonatan , Pérez-Ríos Jesús
Published: November 2024

The Migdal effect is a key inelastic signal channel which could be used to detect low-mass dark matter, but it has never been observed experimentally using Standard Model probes. Here we propose a conceptual design for an experiment which could detect the Migdal effect in diatomic molecules through low-energy neutron scattering, and we provide the requirements on the beam spectrum and reducible backgrounds such that a detection may be achieved. The enhancement of the Migdal rate through non-adiabatic couplings, which are absent in isolated atoms, combined with the distinctive photon energies of electronic transitions in CO, suggest that a positive detection of the molecular Migdal effect may be possible with modest beam times at existing neutron facilities.

Published by the American Physical Society
2024
Advancing set-conditional set generation: Diffusion models for fast simulation of reconstructed particles
Authors: Kobylianskii Dmitrii , Soybelman Nathalie , Kakati Nilotpal , Dreyer Etienne , Nachman Benjamin , Gross Eilam
Published: November 2024

The computational intensity of detector simulation and event reconstruction poses a significant difficulty for data analysis in collider experiments. This challenge inspires the continued development of machine learning techniques to serve as efficient surrogate models. We propose a fast emulation approach that combines simulation and reconstruction. In other words, a neural network generates a set of reconstructed objects conditioned on input particle sets. To make this possible, we advance set-conditional set generation with diffusion models. Using a realistic, generic, and public detector simulation and reconstruction package (COCOA), we show how diffusion models can accurately model the complex spectrum of reconstructed particles inside jets.

Published by the American Physical Society
2024
Supernova Axions Convert to Gamma Rays in Magnetic Fields of Progenitor Stars
Authors: Manzari Claudio Andrea , Park Yujin , Safdi Benjamin R. , Savoray Inbar
Published: November 2024

It has long been established that axions could have been produced within the nascent proto-neutron star formed following the type II supernova SN1987A, escaped the star due to their weak interactions, and then converted to gamma rays in the Galactic magnetic fields; the nonobservation of a gamma-ray flash coincident with the neutrino burst leads to strong constraints on the axion-photon coupling for axion masses ma≲10−10  eV. In this Letter, we use SN1987A to constrain higher mass axions, all the way to ma∼10−3  eV, by accounting for axion production from the Primakoff process, nucleon bremsstrahlung, and pion conversion along with axion-photon conversion on the still-intact magnetic fields of the progenitor star. Moreover, we show that gamma-ray observations of the next Galactic supernova, leveraging the magnetic fields of the progenitor star, could detect quantum chromodynamics axions for masses above roughly 50  μeV, depending on the supernova. We propose a new full-sky gamma-ray satellite constellation that we call the GALactic AXion Instrument for Supernova (GALAXIS) to search for such future signals along with related signals from extragalactic neutron star mergers.

Published by the American Physical Society
2024
Hydrodynamic Equations for Space-Inhomogeneous Aggregating Fluids with First-Principle Kinetic Coefficients
Authors: Osinsky A. I. , Brilliantov N. V.
Published: November 2024

We derive from the first principles new hydrodynamic equations—Smoluchowski-Euler equations for aggregation kinetics in space-inhomogeneous fluids with fluxes. Starting from Boltzmann equations, we obtain microscopic expressions for aggregation rates for clusters of different sizes and observe that they significantly differ from currently used phenomenological rates. Moreover, we show that for a complete description of aggregating systems, novel kinetic coefficients are needed. They share properties of transport and reaction-rate coefficients; for them we report microscopic expressions. For two representative examples—aggregation of particles at sedimentation and aggregation after an explosion—we numerically solve Smoluchowski-Euler equations and perform atomistic simulations by direct simulation Monte Carlo (DSMC). We find that while the new theory agrees well with DSMC results, a noticeable difference is observed for the phenomenological theory. This manifests the unreliability of the currently used phenomenological theory and the need to apply new, first-principle equations.

Published by the American Physical Society
2024
Surplus Indonesia: tackling food waste through app
Authors: Adhariani Desi
Published: November 2024

Learning outcomes

The learning outcomes are as follows: to evaluate the suitability of Surplus business model from accounting, finance, strategy and cultural perspectives; to identify the factors that contribute to the reluctance of business partners to join Surplus ecosystem and to suggest solutions; to identify the factors that contribute to the reluctance of consumers to join Surplus ecosystem and to suggest solutions; and to address unique funding and financial challenges faced by Surplus.

Case overview/synopsis

This case study discussed the challenges faced by Surplus Indonesia, a company founded upon the belief that a harmonious balance can be achieved between profitability and environmental stewardship. Stemming from the founder’s encounter with leftover food going to waste after buffets, Surplus embarked on a pioneering initiative using an application technology to address food wastage at the consumer level. Collaborating with various stakeholders such as retail outlets, restaurants, bakeries, cafes and hotels, the goal was to combat food waste while supporting Sustainable Development Goals 2, 12 and 13: Zero Hunger, Responsible Consumption & Production and Climate Action, respectively. Each meal saved through the Surplus app not only translated to reduced expenses for businesses but also contributed to reducing greenhouse gas emissions from landfills. Surplus’ overarching mission was to cut food waste and loss in Indonesia by half by 2030, fostering an environment where food waste is virtually nonexistent in the nation.

Complexity academic level

Undergraduate as well as graduate courses that focus on sustainability, accounting, financing and strategy

Supplementary material

Teaching notes are available for educators only.

Subject code

CSS 1: Accounting and Finance.
Surviving precarious work: differing forms, tactics and strategies
Authors: Harris Lloyd C. , Ogbonna Emmanuel
Published: November 2024

Purpose

This article explores differentiation in the responses of precarious workers to the instability and uncertainty imposed on their work by employing organizations. Our focus is on the ways in which different workers respond to precarious working conditions, with a particular interest on marginalised groups who have been especially overlooked by studies of workforce precarity.

Design/methodology/approach

Employs an approach akin to grounded theory in an exploratory research design and utilizes in-depth, semi-structured interviews of 56 precarious workers.

Findings

Finds that different precarious workers, with divergent characteristics and resources, facing differing working conditions, and diverse structural constraints vary in the ways in which their strategies of surviving precarious work are manifested. Uncovers three differing forms of precarious workers who each employ a different range of tactics and strategies in work.

Originality/value

Generates insights into differentiation of precarious workers in their responses to the ambiguous, challenging and, in many ways, subjugating conditions of their working conditions.
Extracurricular activities as a pedagogy for the 2030 Agenda integration in an architectural engineering curriculum: a case study
Authors: Elnabawi Mahgoub Mohamed H.
Published: November 2024

Purpose

Considering the lack of integration of sustainable development goals (SDGs) within architectural engineering education, the purpose of this study is to develop a framework that incorporates the SDGs into a programme through extracurricular research activities.

Design/methodology/approach

A framework based on case studies was examined. The framework uses extracurricular activities, including an integrated design process and analytical mapping tool. These were accompanied by a comprehensive list of the 17 SDGs and their interpretations.

Findings

The framework enabled students to develop a systematic understanding of sustainability early on in their design process, leading to a more comprehensive consideration of architectural design issues and increased motivation to prioritise sustainability in architecture.

Research limitations/implications

The focus was on extracurricular activities rather than integrating the framework into the main programme. Therefore, further research is needed to explore this integration within the core curriculum.

Practical implications

The implications of research initiatives and extracurricular activities in promoting understanding of the SDGs among undergraduates were highlighted. The recommendations may be valuable for academic institutions aiming to align their planning in higher education with the necessary skills and global requirements as outlined in Agenda 2030.

Originality/value

The originality of this study lies in its contribution from the field of architectural engineering and its endeavour to incorporate the SDGs into a programme in the Middle East through a research-based approach.
Using genres for laboratory work, report writing and design projects: comparing second and fourth year undergraduate engineers
Authors: Dodson Samuel
Published: November 2024

Purpose

This study aims to investigate patterns of information use among undergraduate engineers as they progress through their academic programs. The primary objective was to discern how second and fourth-year students differ in their use of different types of information while performing specific tasks, namely, conducting labs, composing reports and undertaking projects.

Design/methodology/approach

The research used an online questionnaire to collect data, focusing on the comparative analysis of second and fourth-year engineering students’ information use. The analytical framework comprised a chi-square test, residual analysis and exploratory data analysis, for evaluating statistical significance and identifying trends over time.

Findings

The results demonstrated a statistically significant difference in information use between second and fourth year undergraduates. Notably, fourth year students exhibited a preference for disciplinary genres, such as journal articles, patents and technical reports. This coincided with a decline in fourth year students’ use of educational genres, including textbooks and instructors’ handouts, notes and slides. These shifts in information use were observed consistently across all three tasks.

Originality/value

The uniqueness of the study resides in its innovative approach to exploring information use by investigating the relationship between genres and tasks over the course of students’ academic programs. The research introduces a novel approach for visualizing changes in information use. By describing the evolving preferences of undergraduate students from novice to emerging professional, this study contributes valuable insights into the nuanced ways in which information is used throughout the levels of engineering education.
Comparing the roles of creativity and digital nativity in predicting general and IT innovativeness
Authors: Bunjak Aldijana , Cerne Matej , Philip Jestine , Trkman Peter
Published: November 2024

Purpose

The study compares the effects of creativity and digital nativity, with the latter signifying proficiency in digital skills, on enhancing innovation among employees. The research specifically evaluates the impact of creativity and digital nativity on general innovative performance and personal innovativeness using IT (PIIT).

Design/methodology/approach

Two studies were conducted. Study 1 surveyed 497 individuals on Prolific using objective measures of general innovative performance and self-report measures of PIIT. Study 2 replicated the same research design on Amazon Mechanical Turk with 336 participants and other-rated measures of PIIT.

Findings

Results were consistent across both studies and showed that creativity influenced general innovative performance more than digital nativity. However, digital nativity was a stronger predictor of PIIT, above and beyond the nonsignificant effects of creativity.

Research limitations/implications

This study helps understand the roles that digital nativity and creativity play in general innovative performance and in IT-related innovative performance by providing a relative importance analysis of these components.

Practical implications

We offer guidance to organizations on how to select individuals and assign them to particular tasks depending on digital or general innovative task requirements.

Originality/value

This is the first study to examine the direct comparison of creativity and digital nativity. Although the literature highlights the importance of digital nativity for innovation, our research reveals that creativity is more important for general innovative performance.
On the positive impact of fan communities on brands sponsoring rival teams
Authors: Hickman Thomas M. , Stoica Michael
Published: November 2024

Purpose

The purpose of this study is to determine if regional proximity and fan club involvement could be used to predict success for brands that jointly sponsor a team and their key rival.

Design/methodology/approach

A brand with regional proximity to the rival teams it sponsored was identified. Fan club members of a major college sports team served as respondents. Structural equation modeling was used to test a model that predicted antecedents to purchase intentions and positive word-of-mouth based on individual fan characteristics.

Findings

Results suggest that the intrinsic and social components of fanship as well as regional proximity facilitate the success of brands jointly sponsoring rivals. The intrinsic dimension of fandom foreshadowed approval of the joint sponsorship investigated but did not directly enhance the sponsor’s brand equity. Instead, it was demonstrated that fans must first approve of the joint sponsorship arrangement before conferring elevated brand equity onto the sponsor. Increased social interaction with the fan club resulted in higher levels of purchase intentions and positive word-of-mouth of the joint sponsor.

Originality/value

This study differs from prior studies investigating joint sponsors in four ways. First, the intrinsic and social dimensions of fanship were measured within the context of a fan community. Second, the context of the study included a sponsor with regional proximity to both rival teams. Third, it was determined that the proclivity for social interaction within a fan community enhances the positive outcomes for joint sponsors. Fourth, unlike previous research studying joint sponsors, this study demonstrates a path to success for these brands.
Are we neglecting the influence of national culture (individualism–collectivism index) in mitigating the instances of data breach?
Authors: Gorkhali Anjee , Chowdhury Rajib , Chen Weiru
Published: November 2024

Purpose

Based on neo-institutional theory, this study evaluates factors that affect instances of data breaches in a hospital. The authors study the effect of adopting the health information exchange (HIE) initiative on a hospital’s data breach threats. This study integrates formal and information institutional factors to identify the antecedents that influence data breaches when adopting HIE. This study uses a hospital’s entrepreneurial orientation (EO) as a formal institutional factor and national culture (collectivism–individualism) as an informal institutional factor.

Design/methodology/approach

Using a Statistical Analysis System, the authors analyze US hospital observations over five years. The data was collected from the Health Information and Management Systems Society (HIMSS) database, the Health and Human Services website and the Vandello and Cohen (1999) collectivism index.

Findings

This study finds that when hospitals adopt HIEs, data breaches increase. This study also finds that both EO (formal institutional factor) and the individualism–collectivism index (informal institutional factor) significantly moderate these instances.

Research limitations/implications

HIMSS has not updated its data set to reflect recent hospital data, so this study’s data set lacks recent data on US hospitals.

Originality/value

This study is one of the few studies to address the impact of cultural variation in US hospitals and how it interacts with entrepreneurial activity to lower data breach threats when adopting new data exchange standards.
CCR5 mediates rheumatoid arthritis progression by promoting the activation and proliferation of non‐classical Th1 cells
Authors: Miao Jinlin , Zhang Bei , Sun Haoyang , Zhang Peiyan , Shen Haomiao , Wang Jiawei , Jia Junfeng , Zhang Kui , Zheng Zhaohui , Zhu Ping
Published: November 2024

Aim

Rheumatoid arthritis (RA) is a prevalent autoimmune disease characterized by immune dysegulation, including an immune imbalance due to abnormal activation of non‐classical Th1 cells (CD161+ Th1). This study investigated the effects of CCR5 on the activation and proliferation of CD161+ Th1 and their pathogenicity in patients with RA.

Methods

The study was conducted on 53 patients with RA and 32 age‐ and sex‐matched healthy controls (HC). The cell phenotype was assessed by flow cytometry and the cytokine levels in the supernatant were detected by ELISA.

Results

We demonstrate a marked increase in CD161+ Th1 cells in the synovial fluid of RA patients. These cells exhibit a hyperactivated and hyperproliferative state alongside elevated CCR5 expression. Furthermore, the levels of CD161+ Th1 cells, CD25, and CCR5 in RA synovial fluid show a positive correlation with the disease activity. Additionally, our study reveals that CCR5 facilitates the activation, proliferation, and cytokine production of CD161+ Th1 cells through the pZAP70/NFAT signaling pathway.

Conclusion

These findings contribute to a deeper understanding of RA pathogenesis and uncover a novel mechanism that regulates non‐classical CD161+ Th1 responses in RA, which may provide a potential therapeutic target.
Endogenous Glucagon‐Like Peptide‐1 Receptor and Glucose‐Dependent Insulinotropic Polypeptide Receptor Signaling Inhibits Aeroallergen‐Induced Innate Airway Inflammation
Authors: Toki Shinji , Abney Masako , Zhang Jian , Rusznak Mark , Warren Christian M. , Newcomb Dawn C. , Cahill Katherine N. , Drucker Daniel J. , Niswender Kevin D. , Peebles Ray Stokes
Published: November 2024

Background

Anti‐inflammatory effects of incretin signaling through the glucagon‐like peptide‐1 receptor (GLP‐1R) and the glucose‐dependent insulinotropic polypeptide receptor (GIPR) in mice have been reported. Therefore, we hypothesized that signaling through the endogenous GLP‐1R and the GIPR individually decreases allergic airway inflammation and that the combination of GLP‐1R and GIPR signaling together additively inhibits allergen‐induced lung and airway inflammation.

Methods

WT (C57BL/6J), GLP‐1R knockout (KO), GIPR KO, and GLP‐1R/GIPR double KO (DKO) mice were challenged intranasally with Alternaria alternata extract (Alt‐Ext) or vehicle to evaluate the impact of signaling through these receptors on the innate allergen‐induced inflammatory response that is primarily driven by group 2 innate lymphoid cells (ILC2).

Results

Alt‐Ext‐induced IL‐33 release in the bronchoalveolar lavage fluid (BALF) was not different between the mouse strains, but thymic stromal lymphopoietin (TSLP) was significantly increased in GLP‐1R/GIPR DKO mice challenged with Alt‐Ext compared to the other strains. Furthermore, Alt‐Ext‐induced protein expression of IL‐5, IL‐13, CCL11, and CCL24 in the lung homogenates, the number of eosinophils, lymphocytes, and neutrophils in the BALF, and the number of lung GATA3+ ILC2 were significantly increased in GLP‐1R/GIPR DKO mice compared to the other 3 strains. Furthermore, ICAM‐1 expression on lung epithelial cells was increased in GLP‐1R/GIPR DKO mice challenged with Alt‐Ext compared to the other 3 strains.

Conclusions

Deficiency of both GLP‐1R and GIPR signaling together increased TSLP release, ILC2 activation, and early type 2 innate immune responses to aeroallergen exposure. Combined GLP‐1R and GIPR signaling should be explored for the treatment of asthma.
Every Life Matters: Empowering Care Leavers on Their Path to Independence
Authors: Sharma Girish
Published: November 2024

Following the transition into society, adolescents' rehabilitation and social integration are the main concerns for child care institutions (CCIs). By recognizing the challenges adolescents face, it is possible to facilitate their rehabilitation and integration into society. This study aims to identify the issues and obstacles impeding care leavers' rehabilitation and integration process, as perceived by caregivers. The researcher employs social constructivism as a theoretical framework and qualitative description method as the research design. The study involved eight participants, selected through purposive sampling, and semi‐structured interviews were used to collect data. The study's findings elucidate the risk and protective factors associated with the issues faced by care leavers, including caregiving environment and support, social and community support, educational challenges, psychological and emotional challenges, social isolation and discrimination, among others. Based on the findings, the researcher has developed a Holistic Care Integration and Transition (HCIT) framework for practitioners and policymakers.
Research on Corporate Social Responsibility in Public Relations: A Hybrid Review Through Topic Modeling Analysis and Way Forward
Authors: Çelik Fatih , Koseoglu Mehmet Ali , Ibrahim Blend
Published: November 2024

Despite the growing significance of corporate social responsibility (CSR) in corporate public relations (PR) strategies, there has been a paucity of comprehensive reviews of the extant CSR literature within the PR discipline. The aim of this study is to investigate the relationship between the concept of CSR and the discipline of PR through a hybrid concept‐discipline‐focused review. We employed latent dirichlet allocation (LDA) via topic modeling as a novel approach for intellectual structure analysis. The dataset for this review comprised 246 peer‐reviewed articles on CSR published between 1975 and 2022. Based on the LDA results, five topics were identified and discussed: the political CSR stream, social media‐oriented CSR, consumer‐oriented CSR, CSR reporting, and business‐oriented CSR. Additionally, implications for both academic and practical applications were drawn, along with recommendations for future research. This study is pioneering in its contribution to the literature and practice of CSR‐related PR research, offering insights into the intellectual structures and trends within this field.
CSR Authenticity During Disruptive Events: Exploring Social Media Evaluations of Tesla's Ventilator Initiative in Response to COVID‐19
Authors: Albusaidi Saud Nasser , van den Broek Tijs , Boersma Kees
Published: November 2024

Corporate social responsibility (CSR) initiatives have increasingly become subject to authenticity evaluations on social media. Whilst CSR initiatives are evaluated as authentic if they were perceived to genuinely address societal issues and needs, it is unclear, however, how a disruptive event would change the way stakeholders perceive a company's CSR authenticity. Disruptive events have unique features of urgency, scarcity and uncertainty, which may make stakeholders expect companies to organize their CSR initiatives in different ways in order to be perceived as authentic. Hence, this study aims to explore the conceptualization of CSR authenticity during a disruptive event by analyzing social media evaluations of CSR initiatives. This paper presents the outcomes of an abductive analysis of Twitter evaluations about a respiratory‐ventilator production initiative of Tesla in response to the COVID‐19 crisis. Our findings suggest that three dimensions constitute CSR authenticity during a disruptive event: responsiveness, reliability and motivation. Disruptive events direct the attention of social media users to certain dimensions of CSR authenticity. We discuss the meaning and salience of these dimensions and conclude by implications for theory and practice.
Bringing together but staying apart: decisive differences in animal and fungal mitochondrial inner membrane fusion
Authors: Hashimi Hassan , Gahura Ondřej , Pánek Tomáš
Published: November 2024

Mitochondria are dynamic and plastic, undergoing continuous fission and fusion and rearrangement of their bioenergetic sub‐compartments called cristae. These fascinating processes are best understood in animal and fungal models, which are taxonomically grouped together in the expansive Opisthokonta supergroup. In opisthokonts, crista remodelling and inner membrane fusion are linked by dynamin‐related proteins (DRPs). Animal Opa1 (optical atrophy 1) and fungal Mgm1 (mitochondrial genome maintenance 1) are tacitly considered orthologs because their similar mitochondria‐shaping roles are mediated by seemingly shared biochemical properties, and due to their presence in the two major opisthokontan subdivisions, Holozoa and Holomycota, respectively. However, molecular phylogenetics challenges this notion, suggesting that Opa1 and Mgm1 likely had separate, albeit convergent, evolutionary paths. Herein, we illuminate disparities in proteolytic processing, structure, and interaction network that may have bestowed on Opa1 and Mgm1 distinct mechanisms of membrane remodelling. A key disparity is that, unlike Mgm1, Opa1 directly recruits the mitochondrial phospholipid cardiolipin to remodel membranes. The differences outlined herein between the two DRPs could have broader impacts on mitochondrial morphogenesis. Outer and inner membrane fusion are autonomous in animals, which may have freed Opa1 to repurpose its intrinsic activity to remodel cristae, thereby regulating the formation of respiratory chain supercomplexes. More significantly, Opa1‐mediated crista remodelling has emerged as an integral part of cytochrome c‐regulated apoptosis in vertebrates, and perhaps in the cenancestor of animals. By contrast, outer and inner membrane fusion are coupled in budding yeast. Consequently, Mgm1 membrane‐fusion activity is inextricable from its role in the biogenesis of fungal lamellar cristae. These disparate mitochondrial DRPs ultimately may have contributed to the different modes of multicellularity that have evolved within Opisthokonta.
Rewired chromatin structure and epigenetic gene dysregulation during HTLV‐1 infection to leukemogenesis
Authors: Mizuike Jun , Suzuki Kako , Tosaka Shu , Kuze Yuta , Kobayashi Seiichiro , Nakashima Makoto , Jimbo Koji , Nannya Yasuhito , Suzuki Yutaka , Uchimaru Kaoru , Yamagishi Makoto
Published: November 2024

Human T‐cell leukemia virus type 1 (HTLV‐1) broadly impacts host genes, affecting the infected cell population and inducing the development of a disease with a poor prognosis, adult T‐cell leukemia‐lymphoma (ATL). This study aimed to provide a comprehensive epigenomic characterization of the infected cell population and evaluated the transcriptome and chromatin structures of peripheral blood cells in HTLV‐1‐infected individuals using RNA sequencing (RNA‐seq) and assay for transposase‐accessible chromatin sequencing (ATAC‐seq). The infected cells showed significant changes in gene expression patterns from the polyclonal stage and before ATL onset while demonstrating similarities to tumor‐forming ATL cells. These similarities were a result of large‐scale open chromatin changes, supporting the independent early formation of epigenomic aberrations as an underlying mechanism for later clonal propagation. This study also demonstrated that HTLV‐1 Tax directly affects the host chromatin structure, thereby developing fundamental epigenomic characteristics. Several Tax target genes, including the RASGRP3–ERK pathway, were recognized, indicating an impact on signaling pathways. This genome‐wide variability in chromatin structural property is a novel feature of HTLV‐1 infection and may contribute to pathogenic mechanisms. In addition, it has crucial implications for better understanding the impact of HTLV‐1 on the host genome and identifying novel therapeutic targets.
Association of obesity and metabolic syndrome with incident primary open angle glaucoma in the UK Biobank
Authors: Macri Carmelo Z. , Wong Christopher X. , Tu Samuel J. , Sun David F. , Casson Robert , Singh Kuldev , Wang Sophia , Sun Michelle T.
Published: November 2024

Background

We sought to investigate the association between obesity, metabolic syndrome, and metabolic health with incident primary open‐angle glaucoma (POAG).

Methods

We included 103 249 UK Biobank participants without previously diagnosed glaucoma or glaucoma‐related procedures at enrolment. The primary outcome was POAG identified from diagnostic coding via linked hospital inpatient and primary care data. We used multivariable Cox regression to evaluate the association of body mass index (BMI), and the interaction with metabolic syndrome (MetS) and a novel definition of metabolic health status with incident POAG. BMI was modelled as a time‐varying coefficient. Multivariable analysis was adjusted for age, sex, ethnicity, intraocular pressure, spherical equivalent, polygenic risk score and stratified by the presence of primary care data.

Results

There were 471 events of incident POAG over 464 117 580 person‐years and a mean follow‐up of 12.6 years [Correction added on 18 December 2024, after first online publication: in the “Results” section of the Abstract, the events of incident POAG have been corrected from 647 to 471]. At baseline (time = 0), each one unit increase in BMI was associated with a 9% lower hazard of incident glaucoma (HR 0.91, CI 0.86–0.97, p = 0.0066). Further, compared to a normal BMI range of 18.5–24 kg/m2, a BMI ≥30 kg/m2 was associated with a 65% relative hazard reduction (HR 0.35, CI 0.16–0.80, p = 0.012). There was no significant interaction between BMI and metabolic syndrome or metabolic health (all p > 0.05).

Conclusion

The effect of BMI on the risk of incident POAG varied with time. Higher BMI was associated with a decreased risk of incident POAG in this large prospective cohort. There was no significant association with systemic metabolic health.
Effectiveness of Damoctocog Alfa Pegol to Treat Patients With Hemophilia A Enrolled in the ATHNdataset
Authors: Chandler Martin , Moulton Thomas , Charafi Lena , Charlet Jessica , Recht Michael
Published: November 2024

Objectives

Health information for 17 109 people living with hemophilia A (PLwHA) is contained within the ATHNdataset. We aimed to evaluate the real‐world effectiveness of damoctocog alfa pegol (BAY 94‐9027, Jivi®) for hemophilia A.

Methods

The ATHNdataset was queried for PLwHA receiving damoctocog alfa pegol between January 1, 2010 and April 30, 2022. Data captured via patient charts were analyzed.

Results

At data cutoff, 205 PLwHA were treated with damoctocog alfa pegol: 150 (73.2%) severe (1 female [0.5%]) and 55 (26.8%) mild/moderate (3 [1.5%] female). In total, 32/205 (25.9%) PLwHA received on‐demand treatment; 172 (83.9%) received prophylaxis—161 (93.6%) continuous prophylaxis. Documented bleed rates were available for 187 (91.2%) PLwHA, including those on prophylaxis and on‐demand regimens, with 150 (80.2%) treated for > 12 months. Overall annualized bleeding rates and proportion of PLwHA with zero bleeds, receiving prophylaxis during the observation period, were mean (SD) 0.26 (1.03) and 138/157 (87.9%), respectively. No new or recurring inhibitors were reported.

Conclusion

A low number of bleeds were observed with damoctocog alfa pegol in the real world in both male and female PLwHA. Data should be interpreted with caution owing to limitations of real‐world studies and insubstantial data for female PLwHA.
Automatic responsiveness testing in epilepsy with wearable technology: The ARTiE Watch
Authors: Wheeler Lydia , Kremen Vaclav , Mersereau Cole , Ornelas Guillermo , Yadav Taruna , Cormier Devon , Derry Allyson , Duque Lopez Andrea , McQuown Kevin , Sladky Vladimir , Benjamin Christopher , Giacino Joseph , Worrell Gregory , Blumenfeld Hal ,   START Project Collaborative Team
Published: November 2024

Objective

An accurate evaluation of behavioral responsiveness during and after seizures in people with epilepsy is critical for diagnosis and management. Current methods for assessing behavioral responsiveness are characterized by substantial variation, subjectivity, and limited reliability and reproducibility in ambulatory and epilepsy monitoring unit settings. In this study, we aimed to develop and implement a novel mobile platform for deployment of automated responsiveness testing in epilepsy—the ARTiE Watch—to facilitate standardized, objective assessments of behavioral responsiveness during and after seizures.

Methods

We prospectively recruited patients admitted to the epilepsy monitoring units for diagnostic evaluation and long‐term video‐electroencephalographic monitoring at Mayo Clinic and Yale New Haven Hospital. Participants wore the ARTiE Watch, a smartwatch paired with custom smartphone software integrated with cloud infrastructure allowing for remote activation of standardized assessment on the participants' smartwatches. The assessment consisted of 18 command prompts that test behavioral responsiveness across motor, language, and memory domains. Upon visually identifying an electrographic seizure during EMU monitoring, the BrainRISE platform was used to deploy the ARTiE Watch behavioral testing sequence. Responsiveness scoring was conducted on smartwatch files.

Results

Eighteen of 56 participants had a total of 39 electrographic seizures assessed with the ARTiE Watch. The 18 subjects with ARTiE Watch‐tested seizures had a total of 67 baseline (interictal) ARTiE Watch tests collected for analysis. The analysis showed distinct ARTiE Watch behavioral responsiveness phenotypes: (1) decreased responsiveness across all ARTiE Watch commands during seizure (ictal–postictal) periods compared (to baseline (p < .0001), (2) decreased responsiveness in bilateral tonic–clonic seizures compared to baseline (p < .0001) and compared to focal seizures (p < .0001), and (3) decreased responsiveness during focal impaired awareness seizures compared to baseline (p < .0001) and compared to focal aware seizures (p < .001).

Significance

ARTiE Watch behavioral testing deployed utilizing a mobile cloud‐based platform is feasible and can provide standardized, objective behavioral responsiveness assessments during seizures.
WONOEP appraisal: Targeted therapy development for early onset epilepsies
Authors: Casillas‐Espinosa Pablo M. , Wong Jennifer C. , Grabon Wanda , Gonzalez‐Ramos Ana , Mantegazza Massimo , Yilmaz Nihan Carcak , Patel Manisha , Staley Kevin , Sankar Raman , O'Brien Terence J. , Akman Özlem , Balagura Ganna , Numis Adam L. , Noebels Jeffrey L. , Baulac Stéphanie , Auvin Stéphane , Henshall David C. , Galanopoulou Aristea S.
Published: November 2024

The early onset epilepsies encompass a heterogeneous group of disorders, some of which result in drug‐resistant seizures, developmental delay, psychiatric comorbidities, and sudden death. Advancement in the widespread use of targeted gene panels as well as genome and exome sequencing has facilitated the identification of different causative genes in a subset of these patients. The ability to recognize the genetic basis of early onset epilepsies continues to improve, with de novo coding variants accounting for most of the genetic etiologies identified. Although current disease‐specific and disease‐modifying therapies remain limited, novel precision medicine approaches, such as small molecules, cell therapy, and other forms of genetic therapies for early onset epilepsies, have created excitement among researchers, clinicians, and caregivers. Here, we summarize the main findings of presentations and discussions on novel therapeutic strategies for targeted treatment of early onset epilepsies that occurred during the Workshop on Neurobiology of Epilepsy (WONOEP XVI, Talloires, France, July 2022). The presentations discussed the use of chloride transporter inhibitors for neonatal seizures, targeting orexinergic signaling for childhood absence epilepsy, targeting energy metabolism in Dravet syndrome, and the role of cannabinoid receptor type 2, reversible acetylcholinesterase inhibitors, cell therapies, and RNA‐based therapies in early life epilepsies.