bluuebunny/crossref_metadata_2025 huggingface dataset:
Annotation-preserving machine translation of English corpora to validate Dutch clinical concept extraction tools
Authors: Seinen Tom M , Kors Jan A , van Mulligen Erik M , Rijnbeek Peter R
Published: March 2024

Objective

This work aims to explore the feasibility of validating Dutch concept extraction tools using annotated corpora translated from English, focusing on preserving annotations during translation and addressing the challenge posed by the scarcity of non-English corpora in clinical settings.

Materials and methods

Three annotated corpora were standardized and translated from English to Dutch using two machine translation services, Google Translate and OpenAI GPT-4, with annotations preserved through a proposed method of embedding annotations in the text before translation. The performance of two concept extraction tools, MedSpaCy and MedCAT, was assessed across the corpora in both Dutch and English.

Results

The translation process effectively generated Dutch annotated corpora, allowing the concept extraction tools to perform similarly in both English and Dutch. Although there were some differences in how annotations were preserved across translations, these did not affect extraction accuracy. Supervised MedCAT models consistently outperformed unsupervised models, whereas MedSpaCy demonstrated high recall but lower precision.

Discussion

Our validation of Dutch concept extraction tools on corpora translated from English was successful, highlighting the efficacy of our annotation preservation method and the potential for efficiently creating multilingual corpora. Further improvements and comparisons of annotation preservation techniques and strategies for corpus synthesis could lead to more efficient development of multilingual corpora and more accurate non-English clinical concept extraction tools.

Conclusion

This study has demonstrated that translated English corpora can be effectively used to validate non-English concept extraction tools. The annotation preservation method used during translation proved effective, and future research should aim to extend this corpus translation method to additional languages and clinical settings.
Translational modeling-based evidence for enhanced efficacy of standard-of-care drugs in combination with anti-microRNA-155 in non-small-cell lung cancer
Authors: Dogra Prashant , Shinglot Vrushaly , Ruiz-Ramírez Javier , Cave Joseph , Butner Joseph D. , Schiavone Carmine , Duda Dan G. , Kaseb Ahmed O. , Chung Caroline , Koay Eugene J. , Cristini Vittorio , Ozpolat Bulent , Calin George A. , Wang Zhihui
Published: March 2024

Elevated microRNA-155 (miR-155) expression in non-small-cell lung cancer (NSCLC) promotes cisplatin resistance and negatively impacts treatment outcomes. However, miR-155 can also boost anti-tumor immunity by suppressing PD-L1 expression. We developed a multiscale mechanistic model, calibrated within vivodata and then extrapolated to humans, to investigate the therapeutic effects of nanoparticle-delivered anti-miR-155 in NSCLC, alone or in combination with standard-of-care drugs. Model simulations and analyses of the clinical scenario revealed that monotherapy with anti-miR-155 at a dose of 2.5 mg/kg administered once every three weeks has substantial anti-cancer activity. It led to a median progression-free survival (PFS) of 6.7 months, which compared favorably to cisplatin and immune checkpoint inhibitors. Further, we explored the combinations of anti-miR-155 with standard-of-care drugs, and found strongly synergistic two- and three-drug combinations. A three-drug combination of anti-miR-155, cisplatin, and pembrolizumab resulted in a median PFS of 13.1 months, while a two-drug combination of anti-miR-155 and cisplatin resulted in a median PFS of 11.3 months, which emerged as a more practical option due to its simple design and cost-effectiveness. Our analyses also provided valuable insights into unfavorable dose ratios for drug combinations, highlighting the need for optimizing dose regimen to prevent antagonistic effects. Thus, this work bridges the gap between preclinical development and clinical translation of anti-miR-155 and unravels the potential of anti-miR-155 combination therapies in NSCLC.
Digital Pathology, Deep Learning, and Cancer: A Narrative Review
Authors: Williams Darnell K. Adrian , Graifman Gillian , Hussain Nowair , Amiel Maytal , Priscilla Tran , Reddy Arjun , Haider Ali , Kavitesh Bali Kumar , Li Austin , Alishahian Leael , Perera Nichelle , Efros Corey , Babu Myoungmee , Tharakan Mathew , Etienne Mill , Babu Benson A.
Published: March 2024

Background and Objective

Cancer is a leading cause of morbidity and mortality worldwide. The emergence of digital pathology and deep learning technologies signifies a transformative era in healthcare. These technologies can enhance cancer detection, streamline operations, and bolster patient care. A substantial gap exists between the development phase of deep learning models in controlled laboratory environments and their translations into clinical practice. This narrative review evaluates the current landscape of deep learning and digital pathology, analyzing the factors influencing model development and implementation into clinical practice.

Methods

We searched multiple databases, including Web of Science, Arxiv, MedRxiv, BioRxiv, Embase, PubMed, DBLP, Google Scholar, IEEE Xplore, and Cochrane, targeting articles on whole slide imaging and deep learning published from 2014 and 2023. Out of 776 articles identified based on inclusion criteria, we selected 36 papers for the analysis.

Key Content and Findings

Most articles in this review focus on the in-laboratory phase of deep learning model development, a critical stage in the deep learning lifecycle. Challenges arise during model development and their integration into clinical practice. Notably, lab performance metrics may not always match real-world clinical outcomes. As technology advances and regulations evolve, we expect more clinical trials to bridge this performance gap and validate deep learning models’ effectiveness in clinical care. High clinical accuracy is vital for informed decision-making throughout a patient’s cancer care.

Conclusions

Deep learning technology can enhance cancer detection, clinical workflows, and patient care. Challenges may arise during model development. The deep learning lifecycle involves data preprocessing, model development, and clinical implementation. Achieving health equity requires including diverse patient groups and eliminating bias during implementation. While model development is integral, most articles focus on the pre-deployment phase. Future longitudinal studies are crucial for validating models in real-world settings post-deployment. A collaborative approach among computational pathologists, technologists, industry, and healthcare providers is essential for driving adoption in clinical settings.
Functional analysis of the epilepsy gene Pcdh19 using a novel GFP-reporter mouse model
Authors: Mincheva-Tasheva Stefka , Scherer Michaela , Robertson Louise J. , Piltz Sandra , Bensalem Julien , Pederick Daniel T. , Thomas Paul Q.
Published: March 2024

Mutations in the X-linked genePCDH19are the cause of PCDH19-Clustering epilepsy, an infantile-onset disorder characterized by seizures and intellectual disabilities. Although several intra and extracellular functions of PCDH19 have been identified, the spatiotemporal impact ofPcdh19deletionin vivois poorly understood. To investigate the consequences of eliminatingPcdh19in specific cell and brain regions, we generated a novelPcdh19floxed mouse with a GFP reporter (Pcdh19-cKO-GFP). UsingPcdh19-cKO-GFP andSyn1-Cre mouse lines we demonstrated thatPcdh19elimination in neurons leads to abnormal hippocampal neurogenesis and impaired mouse behaviour. To assess the impact of region-specific elimination ofPcdh19on brain physiology we used aGfap-Cre mice line. SpecificPcdh19deletion in the hippocampus resulted in increased neurogenesis and decreased memory formation. Finally, we assessed the feasibility of using our conditional mouse model for stage-specificPcdh19elimination during embryogenesis using a Dox-inducible Cre-deletor line. Taken together, these results demonstrate the utility of our uniquePcdh19-cKO-GFP mouse model to investigate PCDH19 function in brain physiology and pathology.
Chalkophomycin Biosynthesis Revealing Unique Enzyme Architecture for a Hybrid Nonribosomal Peptide Synthetase and Polyketide Synthase
Authors: Yang Long , Yi Liwei , Gong Bang , Chen Lili , Li Miao , Zhu Xiangcheng , Duan Yanwen , Huang Yong
Published: March 2024

Chalkophomycin is a novel chalkophore with antibiotic activities isolated fromStreptomycessp. CB00271, while its potential in studying cellular copper homeostasis makes it an important probe and drug lead. The constellation ofN-hydroxylpyrrole, 2H-oxazoline, diazeniumdiolate, and methoxypyrrolinone functional groups into one compact molecular architecture capable to coordinate cupric ion draws interest to unprecedented enzymology responsible for chalkophomycin biosynthesis. To elucidate the biosynthetic machinery for chalkophomycin production, thechmbiosynthetic gene cluster from S. sp. CB00271 was identified, and its involvement in chalkophomycin biosynthesis was confirmed by gene replacement. Thechmcluster was localized to a ∼31 kb DNA region, consisting of 19 open reading frames that encode five non-ribosomal peptide synthetase (ChmHIJLO), one modular polyketide synthases (ChmP), six tailoring enzymes (ChmFGMNQR), two regulatory proteins (ChmAB), and four resistance proteins (ChmA′CDE). A model for chalkophomycin biosynthesis is proposed based on functional assignments from sequence analysis and structure modelling, and is further supported by analogy to over 100chm-type gene clusters in public databases. Our studies thus set the stage to fully investigate chalkophomycin biosynthesis and to engineer chalkophomycin analogues through a synthetic biology approach.
Investigating working memory updating processes of the human subcortex using 7T MRI
Authors: Trutti Anne C. , Sjoerds Zsuzsika , Boag Russell J. , Walstra Solenn L.Y. , Miletić Steven , Isherwood Scott S.J. , Bazin Pierre-Louis , Hommel Bernhard , Habli Sarah , Tse Desmond H.Y. , Håberg Asta K. , Forstmann Birte
Published: March 2024

A growing body of research suggests that dopamine is involved in working memory updating and that the striatum takes up a critical role in the subprocess of working memory gating (Braver & Cohen, 2000; Cools & D’Esposito, 2011; D’Ardenne et al., 2012; Jongkees, 2020). In this study, we investigated subcortical–in particular, possible dopaminergic–involvement in working memory updating subprocesses using the reference-back task and ultra-high field 7 Tesla fMRI. Using a scanning protocol optimized for BOLD-sensitivity in the subcortex, we found no evidence of subcortical activation during working memory gate opening, predominantly activations in frontoparietal network regions, which challenges the idea of a striatal gating mechanism. However, during gate closing, subcortical activation was observed. Furthermore, a ready-to-update mode demonstrated large-spread subcortical activation, including basal ganglia nuclei, suggesting that the basal ganglia are engaged in general updating processes rather than specifically controlling the working memory gate. Moreover, substituting new information into working memory elicited activation in dopamine-producing midbrain regions along with the striatum, thalamus, and prefrontal cortex, indicating engagement of the basal ganglia-thalamo-cortical loop possibly driven by (potential) dopaminergic activity. These findings expand our understanding of subcortical regions involved in working memory updating, shifting the focus from gate opening to substitution as a midbrain-driven updating process.
Perceptual awareness of near-threshold tones scales gradually with auditory cortex activity and pupil dilation
Authors: Doll Laura , Dykstra Andrew R. , Gutschalk Alexander
Published: March 2024

Perceptual awareness covaries with negative-going responses in sensory cortex, but the derived concept of perceptual awareness negativity has been criticized a.o. because of its presence for undetected stimuli. To evaluate this objection, we combined magnetoencephalography, electroencephalography, and pupillometry to study the roles of sustained attention and response criterion on the auditory awareness negativity. Participants first detected distractor sounds and denied hearing task-irrelevant near-threshold tones, which evoked neither awareness negativity nor pupil dilation. These same tones evoked responses when task-relevant, stronger for hit but also present for miss trials. To explore if response criterion could explain the presence of responses for miss trials, participants rated their perception on a six-point scale. Decreasing perception ratings were associated with gradually reduced evoked responses, consistent with signal detection theory. These results support the concept of an awareness negativity that is modulated by attention, but does not exhibit a non-linear threshold mechanism.
Developmental assembly of multi-component polymer systems through interconnected gene networksin vitro
Authors: Sorrentino Daniela , Ranallo Simona , Ricci Francesco , Franco Elisa
Published: March 2024

Living cells regulate the dynamics of developmental events through interconnected signaling systems that activate and deactivate inert precursors. This suggests that similarly, synthetic biomaterials could be designed to develop over time by using chemical reaction networks to regulate the availability of assembling components. Here we demonstrate how the sequential activation or deactivation of distinct DNA building blocks can be modularly coordinated to form distinct populations of self-assembling polymers using a transcriptional signaling cascade of synthetic genes. Our building blocks are DNA tiles that polymerize into nanotubes, and whose assembly can be controlled by RNA molecules produced by synthetic genes that target the tile interaction domains. To achieve different RNA production rates, we use a strategy based on promoter “nicking” and strand displacement. By changing the way the genes are cascaded and the RNA levels, we demonstrate that we can obtain spatially and temporally different outcomes in nanotube assembly, including random DNA polymers, block polymers, and as well as distinct autonomous formation and dissolution of distinct polymer populations. Our work demonstrates a way to construct autonomous supramolecular materials whose properties depend on the timing of molecular instructions for self-assembly, and can be immediately extended to a variety of other nucleic acid circuits and assemblies.
Decoding the Cognitive map: Learning place cells and remapping
Authors: Pettersen Markus Borud , Schøyen Vemund Sigmundson , Malthe-Sørenssen Anders , Lepperød Mikkel Elle
Published: March 2024

Hippocampal place cells are known for their spatially selective firing and are believed to encode an animal’s location while forming part of a cognitive map of space. These cells exhibit marked tuning curve and rate changes when an animal’s environment is sufficiently manipulated, in a process known as remapping. Place cells are accompanied by many other spatially tuned cells such as border cells and grid cells, but how these cells interact during navigation and remapping is unknown. In this work, we build a normative place cell model wherein a neural network is tasked with accurate position reconstruction and path integration. Motivated by the notion of a cognitive map, the network’s position is estimated directly from its learned representations. To obtain a position estimate, we propose a non-trainable decoding scheme applied to network output units, inspired by the localized firing patterns of place cells. We find that output units learn place-like spatial representations, while upstream recurrent units become boundary-tuned. When the network is trained to perform the same task in multiple simulated environments, its place-like units learn to remap like biological place cells, displaying global, geometric and rate remapping. These remapping abilities appear to be supported by rate changes in upstream units. While the model does not learn grid-like units, its place cell centers form clusters organized in a hexagonal lattice in open fields. When we decode the center locations of CA1 place fields in mice, we find a similar clustering tendency. This suggests a potential mechanism for the interaction between place cells, border cells, and grid cells. Our model provides a normative framework for learning spatial representations previously reserved for biological place cells, providing new insight into place cell field formation and remapping.
Global 5-methylcytosine-RNA disruption reduces the vectorial competence to DENV2 of heatwave-exposedAedes aegyptimosquitoes
Authors: Claudio-Piedras Fabiola , Recio-Tótoro Benito , Lanz-Mendoza Humberto , Cime-Castillo Jorge
Published: March 2024

Heatwaves are an increasingly common environmental event linked with climate change. Abnormally high heatwave temperatures can affect several mosquito vector traits that are determinants of pathogen transmission. Understanding how these mosquitoes adapt to high heat is vital for global public health. RNA methylation, a key cellular mechanism in stress response and adaptation, remains understudied in mosquito vector competence and heat stress responses. This study investigates the role of RNA methylation in mosquito responses to heatwaves and its influence on DENV2 vector competence. Heatwave-exposed and DENV-infected mosquitoes presented lower survivorship and lower antiviral transcriptional response, developed high infection rates, and increased the life expectancy of infected mosquitoes during the period of highest virus transmissibility. In contrast, inhibition of RNA methylation in heatwave-treated mosquitoes increased survivorship and the antiviral transcriptional response, reducing infection prevalence from 78% to 37%. These results indicate that the RNA methylation background in mosquitoes favors vector competence for DENV2 during a heatwave exposure, and points towards possible interventions to countermeasure the effect of climate change on DENV transmission.
Venom gland organogenesis in the common house spider
Authors: Hassan Afrah , Blakeley Grace , McGregor Alistair P. , Zancolli Giulia
Published: March 2024

Venom is a remarkable innovation found across the animal kingdom, yet the evolutionary origins of venom systems in various groups, including spiders, remain enigmatic. Here, we investigated the organogenesis of the venom apparatus in the common house spider,Parasteatoda tepidariorum. The venom apparatus consists of a pair of secretory glands, each connected to an opening at the fang tip by a duct that runs through the chelicerae. We performed bulk RNA-seq to identify venom gland-specific markers and assayed their expression using RNAin situhybridisation experiments on whole-mount time-series. These revealed that the gland primordium emerges during embryonic stage 13 at the chelicera tip, progresses proximally by the end of embryonic development and extends into the prosoma post-eclosion. The initiation of expression of an important toxin component in late postembryos marks the activation of venom-secreting cells. Our selected markers also exhibited distinct expression patterns in adult venom glands:sageand the toxin marker were expressed in the secretory epithelium,forkheadandsum-1in the surrounding muscle layer, whileDistal-lesswas predominantly expressed at the gland extremities. Our study provides the first comprehensive analysis of venom gland morphogenesis in spiders, offering key insights into their evolution and development.
Kitaev-Heisenberg model on the star lattice: From chiral Majorana fermions to chiral triplons
Authors: d'Ornellas P. , Knolle J.
Published: March 2024

The interplay of frustrated interactions and lattice geometry can lead to a variety of exotic quantum phases. Here we unearth a particularly rich phase diagram of the Kitaev-Heisenberg model on the star lattice, a triangle decorated honeycomb lattice breaking sublattice symmetry. In the antiferromagnetic regime, the interplay of Heisenberg coupling and geometric frustration leads to the formation of valence bond solid (VBS) phases—a singlet VBS and a bond selective triplet VBS stabilized by the Kitaev exchange. We show that the ratio of the Kitaev versus Heisenberg exchange tunes between these VBS phases and chiral quantum spin-liquid regimes. Remarkably, the VBS phases host a whole variety of chiral triplon excitations with high Chern numbers in the presence of a weak magnetic field. We discuss our results in light of a recently synthesized star lattice material and other decorated lattice systems.

Published by the American Physical Society
2024
Sterile neutrino portal dark matter from semiproduction
Authors: Liu Ang , Shao Feng-Lan , Han Zhi-Long , Jin Yi , Li Honglei
Published: March 2024

In this paper, we study the feeble sterile neutrino portal dark matter under the Z3 symmetry. The dark sector consists of one fermion singlet χ and one scalar singlet χ, which transform as χ→ei2π/3χ,ϕ→ei2π/3ϕ under the Z3 symmetry. Regarding fermion singlet χ as the dark matter candidate, the new interaction terms yχϕχc¯χ and μϕ3/2 could induce various new production channels. For instance, when mϕ>2mχ, the pair decay ϕ→χχ could be the dominant channel, rather than the delayed decay ϕ→χν. Another appealing scenario is when the dark sector is initially produced through the scattering process as NN→χχ,NN→ϕϕ,hν→χϕ, then the semiproduction processes Nχ→ϕϕ,Nϕ→ϕχ,Nχ→χχ could lead to the exponential growth of dark sector abundances. The phenomenology of the sterile neutrino and the cosmological impact of the dark scalar are also considered in the Z3 symmetric model.

Published by the American Physical Society
2024
Direct Observation of Sub-Poissonian Temporal Statistics in a Continuous Free-Electron Beam with Subpicosecond Resolution
Authors: Borrelli S. , de Raadt T. C. H. , van der Geer S. B. , Mutsaers P. H. A. , van Leeuwen K. A. H. , Luiten O. J.
Published: March 2024

We present a novel method to measure the arrival time statistics of continuous electron beams with subpicosecond resolution, based on the combination of an rf deflection cavity and fast single electron imaging. We observe Poissonian statistics within time bins from 100 to 2 ns and increasingly pronounced sub-Poissonian statistics as the time bin decreases from 2 ps to 340 fs. This 2D streak camera, in principle, enables femtosecond-level arrival time measurements, paving the way to observing Pauli blocking effects in electron beams and thus serving as an essential diagnostic tool toward degenerate electron beam sources for free-electron quantum optics.

Published by the American Physical Society
2024
Scaling Description of Frictionless Dense Suspensions under Inhomogeneous Flow
Authors: Bhowmik Bhanu Prasad , Ness Christopher
Published: March 2024

Predicting the rheology of dense suspensions under inhomogeneous flow is crucial in many industrial and geophysical applications, yet the conventional “μ(J)” framework is limited to homogeneous conditions in which the shear rate and solids fraction are spatially invariant. To address this shortcoming, we use particle-based simulations of frictionless dense suspensions to derive new constitutive laws that unify the rheological response under both homogeneous and inhomogeneous conditions. By defining a new dimensionless number associated with particle velocity fluctuations and combining it with the viscous number, the macroscopic friction, and the solids fraction, we obtain scaling relations that collapse data from homogeneous and inhomogeneous simulations. The relations allow prediction of the steady state velocity, stress, and volume fraction fields using only knowledge of the applied driving force.

Published by the American Physical Society
2024
Co-creation and innovation in higher education institutions: a systematic literature review and research agenda
Authors: Oliveira Tiago , Alves Helena , Leitão João
Published: March 2024

Purpose

This systematic literature review aims to identify the main areas of study related to co-creation and innovation in Higher Education Institutions (HEIs), as well as the main external and internal stakeholders with whom co-creation is made.

Design/methodology/approach

The empirical approach is based on 258 articles selected from the Web of Science (WoS), Clarivate Analytics and Scopus, Elsevier databases, with analysis of titles, abstracts and keywords following a research protocol. VOS viewer and CitNetExplorer software were used, with the twin aim of identifying publications with a higher number of citations and designing maps of reference word co-occurrence.

Findings

The analysis led to three clusters being identified: Cluster 1. Management and transfer of knowledge from HEIs to companies; Cluster 2. Co-creation and innovation in HEIs through cooperation between universities and companies; and Cluster 3. Universities’ third mission and their role in developing entrepreneurship education. The results of the literature clusters analysis led to proposing a conceptual model of analysis.

Research limitations/implications

Despite only employing two databases and the content analysis criteria, the three found clusters are linked, recognising the interplay between co-creation and innovation in HEIs, knowledge transfer to enterprises and the influence on HEIs' third goal.

Practical implications

This systematic literature review highlights and gives a picture of the state-of-the-art in co-creation and innovation in HEIs, as well as presenting a model of co-creation and innovation in HEIs that can contribute to reinforcing the University-Industry-Community ties.

Social implications

This study can lead to a better knowledge of the issue of co-creation and innovation at HEIs, as well as a deeper analysis of the sorts of relationships between HEIs and their stakeholders, as well as its impact on surrounding areas and influence.

Originality/value

The research highlights the interaction between HEIs and their stakeholders on a basis of value co-creation and innovation, providing mutual benefits for all involved, as well as greater development and recognition of HEIs and their surrounding regions’ image andreputation. A future research agenda is also presented on the topic of co-creation and innovation in HEIs.
Development of a self-reflection scale for observers of mathematics lesson during lesson study
Authors: Sakai Takeshi , Akai Hideyuki , Ishizaka Hiroki , Tamura Kazuyuki , Choy Ban Heng , Lee Yew-Jin , Ozawa Hiroaki
Published: March 2024

Purpose

This study aims to develop a self-reflection scale useful for teachers to improve their skills and to clarify the Japanese teachers’ characteristics during mathematics lesson observation (MLO). In MLO, it is important to understand the lesson plan in advance to clarify observation points, and we aim to develop a scale including these points.

Design/methodology/approach

Based on the pre-questionnaire survey, nine perspectives and two situations for MLO were extracted. From these, a questionnaire for MLO was created. The results obtained from 161 teachers were examined, and exploratory factor analysis was conducted. ANOVA was conducted to analyze the effect of differences across the duration of teaching experience on the identified factors.

Findings

We developed a self-reflection scale consisting of 14 items with three factors: [B1] focus on instructional techniques and evaluation, [B2] focus on proactive problem-solving lesson development and [B3] focus on the mathematical background of the learning content. While duration of teaching experience showed no effect, three factors of the self-reflection scale for MLO showed a significant effect. Further multiple comparisons revealed the degree of focus was [B2]>[B1]>[B3].

Originality/value

Teachers who use this developed scale may grasp the strengths and weaknesses of their own MLO, which leads to self-improvement. The perspectives emphasized in lesson observation are the same when creating lesson plans and implementing lessons, leading to lesson improvement. Furthermore, based on the characteristics of teachers revealed, new training programs regarding MLO can lead to higher-quality lesson studies.
Marketing beyond reality: a systematic literature review on metaverse
Authors: Yadav Sakshi , Pandey Shivendra Kumar , Sharma Dheeraj
Published: March 2024

Purpose

This study aims to answer two significant questions: What are the relative consumer and firm-level effects of marketing through metaverse compared to conventional marketing endeavours? What are the current trends in utilizing the metaverse as reported in the recent literature?

Design/methodology/approach

This study uses a systematic literature review methodology, using a Preferred Reporting Items for Systematic Reviews and Meta-Analyses flowchart to synthesize existing research. A total of 35 articles written in English were selected and analysed from two databases, Web of Science and EBSCO Host.

Findings

The findings indicate that consumer-level effects of the metaverse include consumer loyalty and brand attachment. The firm-level benefits are decentralization and cost reductions. The paper proposes a framework indicating variables that could attenuate or enhance the association between immersive components of the metaverse and their resultant effects.

Originality/value

This study contributes to understanding the role of metaverse in marketing practices related to the marketing mix components. The study conceptualizes a novel framework for the metaverse and its resultant effects.
Police custody in rural Scotland: negotiating boundaries, risk and organisational change
Authors: Wooff Andrew
Published: March 2024

Purpose

This paper explores the challenging nexus of police custody, risk and intra-organisational boundaries in the context of a recently reformed national police service. Police custody is an often-hidden aspect of policing, away from the public gaze and scrutiny. Although there is increasing recognition of the importance of rural policing (e.g. Harkness (2020); Mawby and Yarwood (2011); Ruddell and Jones (2020); Yarwood and Wooff (2016)), there has been little or no focus on rural police custody. This paper seeks to begin to redress this by focussing on the challenges faced by rural police custody in the context of large-scale organisational change.

Design/methodology/approach

This paper draws on data from a study funded by the Scottish Institute for Policing Research (2016–2018), entitled “Measuring Risk and Efficiency in Police Custody in Scotland”. The paper adopts a qualitative methodology to develop an understanding of the varying nature of police custody across Scotland. Two contrasting case study locations were selected, one urban and one rural. 12 semi-structured interviews and 15 hours of observation were carried out. Data was transcribed, coded and analysed and thematic analysis enabled themes to be developed. This paper draws on the data from the rural custody suite.

Findings

Drawing on the theoretical framework of Giacomantonio (2014) and more recent considerations of abstract policing Terpstra et al. (2019), this paper offers insights into the ways that police custody in rural Scotland has been organised, against the backdrop of challenging organisational change. I argue that as policing services in Scotland have become increasingly “abstract” from communities, police custody as a national division has witnessed the impact of this more greatly than other parts of local policing. Intra-organisational management around staffing has led to complex management of risk, illustrating some of the challenges of national organisational change on police custody.

Originality/value

This paper focuses on the impact of large scale organisational change on rural police custody and intra-organisational relationships and dynamics. Rural policing is still a largely neglected area of study and rural police custody is even less understood. This paper therefore provides an original contribution by focusing on this under-researched area of policing. It also illustrates complexity around risk, staffing and management of people being held in rural police custody suites. It is therefore of value to policing scholars in other contexts, as well as rural criminology more generally. It has applicability to international contexts where macro level policing reform is occurring.
Thermoregulation enhances survival but not reproduction in a plant‐feeding insect
Authors: Leith Noah T. , Miller Em A. , Fowler‐Finn Kasey D.
Published: March 2024

Temperature influences nearly all aspects of fitness. However, reproduction is often more thermally sensitive than survival. Thermoregulation must maintain performance in both components of fitness to buffer populations from environmental change.

We assessed the fitness benefits of thermoregulation in Enchenopa binotata treehoppers. Under realistic mesocosm conditions, we quantified fine‐scale microclimates using 3D‐printed operative temperature models. We then compared operative temperatures to treehopper body temperatures and translated patterns of thermoregulation into variation in survival and reproduction. We also assessed two thermoregulatory mechanisms: precise microclimate choice and heat‐escape behaviours. Finally, we applied our results to evaluate if arthropod thermoregulation is accurately characterized by two theoretical models commonly used to simulate responses to environmental change.

We found substantial thermal variation at fine spatial scales relevant to insects: at a single point in time, temperatures within 30‐cm‐tall plants spanned ranges up to 19°C (23–42°C).

Lethal operative temperatures were common when air temperatures were high. However, heat escapes allowed treehoppers to almost entirely avoid lethal temperatures.

By contrast, individuals thermoconformed in the absence of lethal operative temperatures. This finding suggests that precise microclimate choice imposes high costs due to thermal uncertainty at fine spatial scales. Furthermore, given the narrow range of temperatures in which reproduction occurs, thermoregulation is unlikely to maintain reproduction.

Thermoregulation was most effective in the lowest‐quality and most spatially variable thermal habitats. Treehopper thermoregulation therefore more closely follows cost–benefit models of thermoregulation compared to models that account for inhibited movement at extreme temperatures.

Overall, even if thermoregulation can prevent lethal heat stress, it may have limited capacity to buffer arthropods and other small ectotherms from environmental change if it cannot maintain reproductive performance.

Read the free Plain Language Summary for this article on the Journal blog.
Markups in US food manufacturing accounting for non‐neutral productivity
Authors: Jaumandreu Jordi , Lopez Rigoberto
Published: March 2024

We examine the evolution of productivity and markups in US food and beverage manufacturing from 1959 through 2018. We account for non‐Hicks‐neutral (labour‐augmenting) productivity changes and compare markups with those in general manufacturing using the same dataset and model. We also compare our results with those of the increasingly popular De Loecker and Warzynski (2012, American Economic Review, 102, 2437) method, which does not account for non‐Hicks‐neutral productivity growth. Empirical results show that productivity growth in the food and beverage sector has been relatively slow and driven with equal intensity by Hicks‐neutral and labour‐augmenting productivity gains. General manufacturing shows higher productivity growth that is mostly labour‐augmenting, with markups comparable to those of food manufacturing. We find that accounting for labour‐augmenting productivity produces more moderate markup estimates than the De Loecker and Warzynski (2012) method. We also find no evidence of markups rising in either food manufacturing or general manufacturing in the last 20 years, in contrast to much of the recent economic literature.
Impact of HER2‐low expression on the efficacy of endocrine therapy with or without CDK4/6 inhibitor in HR‐positive/HER2‐negative metastatic breast cancer: A prospective study
Authors: Wu Yun , Mo Hongnan , Xu Hangcheng , Wang Yan , Wang Jiayu , Ma Fei , Xu Binghe
Published: March 2024

Background

CDK4/6 inhibitors in combination with traditional endocrine therapy (ET) have become the recommended first‐line therapy for HR‐positive/HER2‐negative metastatic breast cancer (MBC). The aim of this prospective study was to evaluate the relationship between HER2‐low expression and clinical outcomes in HR‐positive/HER2‐negative MBC patients receiving ET with or without CDK4/6 inhibitors.

Methods

Between April 2016 and November 2019, 233 women with HR‐positive/HER2‐negative MBC who received ET with or without CDK4/6 inhibitors were enrolled into the study. The primary endpoint was progression‐free survival (PFS). Statistical analysis included descriptive statistics, Kaplan–Meier curves, and Cox proportional hazards models.

Results

HER2‐low and HER2‐zero subgroups in the CDK4/6 inhibitor plus ET cohort showed no significant difference in the median PFS (10.9 vs. 8.0 months; hazard ratio: 0.92; 95% confidence interval [CI]: 0.64–1. 30; p = 0.65), while HER2‐low subgroup showed a significantly shorter median PFS compared to the HER2‐zero subgroup in the ET alone cohort (5.6 vs. 17.0 months; hazard ratio: 2.82; 95% CI: 1.34–5.93; p = 0.0044). Moreover, the objective response rate was significantly lower in the HER2‐low subgroup than the HER2‐zero subgroup in the ET alone cohort (10.5% vs. 40.0%, p = 0.047). Lastly, no significant difference was observed in the overall survival between the HER2‐low and HER2‐zero subgroups in both cohorts.

Conclusion

This study suggested that HER2‐low expression may predict the efficacy of ET but not that of CDK4/6 inhibitor plus ET in HR‐positive/HER2‐negative MBC patients. The results of this study highlight the importance of integrating HER2 status in tailoring personalized treatment strategies for HR‐positive MBC.
Investigating the dissociative subtype of post‐traumatic stress disorder in single‐ and multi‐event trauma‐exposed youth: Prevalence, course, prognosis, severity and functional impairment
Authors: White William F. , Burgess Aaron , Dalgleish Tim , Dixon Clare , Halligan Sarah L. , Hiller Rachel M. , McKinnon Anna , Smith Patrick , Meiser‐Stedman Richard
Published: March 2024

Objectives

This study aimed, following both single‐ and multi‐event trauma, to ascertain prevalence and course of the dissociative subtype of post‐traumatic stress disorder (PTSD‐DS) in youth; how well early PTSD‐DS predicts later PTSD; and whether dissociation accounts for unique variance in post‐traumatic stress symptoms (PTSS) and functional impairment over and above the effect of other post‐trauma cognitive processing factors and PTSS respectively.

Design and Methods

This study is a secondary analysis of data from the Acute Stress Programme for Children and Teenagers study (n = 234) and the Coping in Care After Trauma study (n = 110) in which children had experienced single‐ and multi‐event trauma respectively.

Results

PTSD‐DS diagnosis was common in children with PTSD regardless of trauma experienced (>39.0%). PTSD‐DS showed a similar trajectory of natural recovery to PTSD, and it was similarly predictive of later PTSD following single‐event trauma. Finally, dissociation was a significant factor in PTSS and functional impairment.

Conclusions

These results should be viewed in the context of several limitations including narrow sample of participants which reduces the generalizability of results, concerns around children's ability to conceptualize challenging concepts such as dissociation and the use of self‐report measures to form diagnostic groups. The PTSD‐DS diagnosis may offer clinical utility to the extant PTSD diagnosis in children and adolescents, as dissociation has been shown to be a contributory factor in the maintenance of both PTSS and functional impairment. Further research is required to inform further editions of the DSM and other diagnostic systems.
Efficacy and predictors of immune checkpoint inhibitors in patients with gallbladder cancer
Authors: Cheng Zhuo , Yang Cheng , Zhao Qian , Zhong Jingjiao , Zhang Jin , Jin Riming , Li Yao , Ta Na , Wu Dong , Yuan Zhengang , Sun Wen , Wang Ruoyu
Published: March 2024

Immune checkpoint inhibitors (ICIs) have shown promising efficacy in multiple cancers including biliary tract cancers (BTCs). However, the data focusing on the efficacy of ICIs in patients with gallbladder cancer (GBC) is still limited. In this study, we aim to assess the efficacy of ICIs in GBC and explore the clinicopathologic and molecular markers associated with ICI benefit. We retrospective analyzed 69 GBC patients who had received ICI therapy between January 2016 and December 2020. Tumor samples were obtained for genomic sequencing and immunohistochemical analysis. The median progression‐free survival (PFS) and overall survival (OS) was 4.4 months and 8.5 months, respectively. Multivariate analysis indicated that alcohol intake history, carcinoma embryonic antigen (CEA) level ≥100 U/mL, and cutaneous immune‐related adverse events (irAEs) were independent prognostic factors for PFS. CEA level ≥100 U/mL and cutaneous irAEs were independent prognostic factors for OS. The objective response rate and disease control rate (DCR) were 15.9% and 37.7%, respectively. Patients with cutaneous irAEs, high CD8+ T cell infiltrated or immune inflamed GBCs had higher DCR. Patients with high CD8+ T cell infiltrated or immune inflamed GBCs also had a notably improved prognosis. These results suggest that ICIs were effective in patients with GBC. High CEA level, cutaneous irAEs, high CD8+ T cell infiltration, and immune inflamed phenotype could be useful for predicting the efficacy of ICIs in GBC.
A nationwide registry‐based observational study of thyroid disease incidence in the Faroe Islands
Authors: Johannesen Herborg Líggjasardóttir , Veyhe Anna Sofía , Andreassen Jens , Weihe Pál , Strøm Marin , Andorsdóttir Guðrið , Rasmussen Aase Krogh , Feldt‐Rasmussen Ulla , Carlé Allan , Andersen Stig
Published: March 2024

Objective

The occurrence of thyroid disease varies among populations. While the iodine nutrition level of the Faroese seems to have been decreasing over the past decades, there is no systematic evaluation of the thyroid disease pattern in the Faroe Islands. Such knowledge of thyroid disease occurrence in the North Atlantic region may support healthcare planning and prevention. To investigate incidence rates, including subtypes of thyroid diseases, and demographic characteristics of thyroid disease patients in the Faroe Islands, to improve understanding of the patterns and trends of these disorders.

Design and Method

A registry‐based observational study was conducted over 10 years, encompassing all adult Faroese individuals. Patients and Measurements: Health records from general practitioners and hospitals were used to identify incident cases of thyroid diseases. Validation was performed using multiple data sources. The incidence rates were standardised using population data from the middle of the study period 2006–2018.

Results

Among the 1152 individuals diagnosed with thyroid disease, the standardised incidence rates per 100,000 person‐years were 55 for hyperthyroidism and 112 for hypothyroidism, and around four times higher in women than in men. Hashimoto's thyroiditis was the dominant cause of hypothyroidism, while Graves' disease was the leading cause of hyperthyroidism. The incidence of hypothyroidism increases with age. A decreasing trend was observed over time for both hypothyroidism and hyperthyroidism.

Conclusion

Considering the decrease in iodine nutrition levels over the past decades, we were surprised by the high incidence of autoimmune thyroid disease. The findings highlight the need for continuous monitoring of thyroid disease occurrence in coastal areas of the North Atlantic Ocean.
Improving multidisciplinary management of patients living with obesity: The evaluation of seated bioimpedance measures and relationship to functional performance following targeted intervention
Authors: Ryan Elizabeth , MacLaughlin Helen , Hay Robin , Cawte Andrea , Naumann Leonie , Woodruff Gemma , Cottrell Michelle , Window Peter
Published: March 2024

Management of obesity requires a multidisciplinary approach including physical activity interventions, which have significant impacts on overall health outcomes. Greater levels of lean muscle mass are significantly associated with improved health and reduced risk of comorbidities and should be preserved where possible when undertaking rapid weight loss. This article reports on the physical and functional outcomes achieved during a 12‐week intensive multidisciplinary intervention targeting obesity and evaluates correlations between body composition and functional outcomes. We additionally aimed to investigate the test–retest reliability and levels of agreement in body composition measurements using bioimpedance spectroscopy between seated and standing positions. Of the 35 participants included in analysis, significant differences were observed between baseline and post‐intervention measures. These included weight loss of 12.6 kg, waist circumference reduction of 10.5 cm, fat mass reduction by 2.9%, muscle mass increase by 1.6%, 54.5 m improvement in the 6‐minute walk test and 3.8 rep improvement in the 30‐second sit‐to‐stand test. No significant correlations were observed between physical and functional outcome measures. Excellent test re‐test reliability was observed in bioimpedance spectroscopy seated measurements (ICC >.9). Significant differences were observed between seated and standing bioimpedance spectroscopy measurements, however they are regarded as small differences in a clinical setting.
Enriching Thinking Through Discourse
Authors: Kuhn Deanna , Bruun Sybille , Geithner Caroline
Published: March 2024

Great effort is invested in identifying ways to change people's minds on an issue. A first priority should perhaps be enriching their thinking about the issue. With a goal of enriching their thinking, we studied the views of community adults on the DACA issue—young adults who entered the United States illegally as children. A dialogic method was employed, offering dual benefits in providing participants the opportunity to further develop their own ideas and to consider differing ideas. Yet, participants engaged in dialog only vicariously by observing the talk of a pair of actors who held opposing positions on DACA. The effect on participants’ thinking was greatest in the condition in which they viewed a dialog between the two actors, rather than a comparison condition in which the actors individually expressed their positions. In control conditions, no presentation was observed. Probing questions included in all conditions encouraged a participant to examine and clarify for themselves their own position, potentially enriching it. This condition proved unsuccessful in enriching thinking; participants’ justifications for their own positions in fact became simpler and less qualified. In contrast, observing a video of a like‐minded and opposing other did enrich observers’ thinking, yet to a greater degree in the dialogic than nondialogic condition. The findings thus suggest observed dialog as a promising practical approach in promoting deeper thinking.