bluuebunny/crossref_metadata_2025 huggingface dataset:
Calcium phosphate nanoclusters modify periodontium remodeling and minimize orthodontic relapse
Authors: Cuylear Darnell L. , Fu Moyu L. , Chau Justin C. , Kharbikar Bhushan , Kazakia Galateia J. , Jheon Andrew , Habelitz Stefan , Kapila Sunil D. , Desai Tejal A.
Published: July 2024

Orthodontic relapse is one of the most prevalent concerns of orthodontic therapy. Relapse results in patients’ teeth reverting towards their pretreatment positions, which increases the susceptibility to functional problems, dental disease, and substantially increases the financial burden for retreatment. This phenomenon is thought to be induced by rapid remodeling of the periodontal ligament (PDL) in the early stages and poor bone quality in the later stages. Current therapies, including fixed or removable retainers and fiberotomies, have limitations with patient compliance and invasiveness. Approaches using biocompatible biomaterials, such as calcium phosphate polymer-induced liquid precursors (PILP), is an ideal translational approach for minimizing orthodontic relapse. Here, post-orthodontic relapse is reduced after a single injection of high concentration PILP (HC-PILP) nanoclusters by altering PDL remodeling in the early stage of relapse and improving trabecular bone quality in the later phase. HC-PILP nanoclusters are achieved by using high molecular weight poly aspartic acid (PASP, 14 kDa) and poly acrylic acid (PAA, 450 kDa), which resulted in a stable solution of high calcium and phosphate concentrations without premature precipitation.In vitroresults show that HC-PILP nanoclusters prevented collagen type-I mineralization, which is essential for the tooth-periodontal ligament (PDL)-bone interphase.In vivoexperiments show that the PILP nanoclusters minimize relapse and improve the trabecular bone quality in the late stages of relapse. Interestingly, PILP nanoclusters also altered the remodeling of the PDL collagen during the early stages of relapse. Furtherin vitroexperiments showed that PILP nanoclusters alter the fibrillogenesis of collagen type-I by impacting the protein secondary structure. These findings propose a novel approach for treating orthodontic relapse and provide additional insight into the PILP nanocluster’s structure and properties on collagenous structure repair.
Shifts in neural tuning systematically alter sensorimotor learning ability
Authors: Hayashi Takuji , Takiyama Ken , Smith Maurice A. , Nozaki Daichi
Published: July 2024

Sensorimotor learning can change the tuning of neurons in motor-related brain areas and rotate their preferred directions (PDs). These PD rotations are commonly interpreted as reflecting motor command changes; however, cortical neurons that display PD rotations also contribute to sensorimotor learning. Sensorimotor learning should, therefore, alter not only motor commands but also the tuning of neurons responsible for this learning, and thus impact subsequent learning ability. Here, we investigate this possibility with computational modeling and by directly measuring adaptive responses during sensorimotor learning in humans. Modeling shows that the PD rotations induced by sensorimotor learning, predict specific anisotropic changes in PD distributions that in turn predict a specific spatial pattern of changes in learning ability. Remarkably, experiments in humans then reveal large, systematic changes in learning ability in a spatial pattern that precisely reflects these model-predicted changes. We find that this pattern defies conventional wisdom and implements Newton’s method, a learning rule where the step size is inversely proportional rather than proportional to the learning gradient’s amplitude, limiting overshooting in the adaptive response. Our findings indicate that PD rotation provides a mechanism whereby the motor system can simultaneously learn how to move and learn how to learn.
Cell binding, uptake and infection of influenza A virus using recombinant antibody-based receptors
Authors: Adu Oluwafemi F. , Borau Milagros Sempere , Früh Simon , Karakus Umut , Weichert Wendy S. , Wasik Brian R. , Stertz Silke , Parrish Colin R.
Published: July 2024

Human and avian influenza A viruses bind to sialic acid (Sia) receptors on cells as their primary receptors, and this results in endocytic uptake of the virus. While the role of Sia on glycoproteins and/or glycolipids for virus entry is crucial, the roles of the carrier proteins are still not well understood. Furthermore, it is still unclear how receptor binding leads to infection, including whether the receptor plays a structural or other roles beyond being a simple tether. To enable the investigation of the receptor binding and cell entry processes in a more controlled manner, we have designed a protein receptor for pandemic H1 influenza A viruses. The engineered receptor possesses the binding domains of an anti-HA antibody prepared as a single chain variable fragment (scFv) fused with the stalk, transmembrane and cytoplasmic sequences of the feline transferrin receptor type-1 (fTfR). When expressed in cells that lack efficient display of Sia due to a knockout of theSlc35A1gene which encodes for the Solute Carrier Family 35 transporter (SLC35A1), the anti-H1 receptor was displayed on the cell surface, bound virus or hemagglutinin proteins, and the virus was efficiently endocytosed into the cells. Infection occurred at similar levels to those seen after Sia reconstitution, and treatment with clathrin-mediated endocytosis (CME) inhibitors significantly reduced viral entry.

IMPORTANCE.

Influenza A viruses mostly circulate among avian reservoirs, and also can jump hosts to cause epidemics in mammals, including among humans. A key interaction of the viruses is with host cell Sia, which vary in chemical form, in their linkages within the oligosaccharide, and in the attachment to surface glycoproteins or glycolipids with different properties. Here we report a new method for examining the processes of receptor binding and uptake into cells during influenza A virus infection, by use of an engineered HA-binding membrane glycoprotein, where an antibody is used as the binding domain and the transferrin receptor uptake structures mediate efficient entry, which should allow us to test and manipulate the processes of cell binding, entry, and infection.
Ca2+-driven PDIA6 phase separation to ensure proinsulin quality control
Authors: Lee Young-Ho , Saio Tomohide , Watabe Mai , Matsusaki Motonori , Kanemura Shingo , Lin Yuxi , Mannen Taro , Kuramochi Tsubura , Iuchi Katsuya , Tajiri Michiko , Suzuki Kotono , Li Yan , Heo Yunseok , Kamada Yuka , Arai Kenta , Hashimoto Mayuko , Ninagawa Satoshi , Hattori Yoshikazu , Kumeta Hiroyuki , Takeuchi Airu , Abe Hiroya , Mori Eiichiro , Muraoka Takahiro , Okiyoneda Tsukasa , Akashi Satoko , Vendruscolo Michele , Inaba Kenji , Okumura Masaki
Published: July 2024

The endoplasmic reticulum (ER) plays key roles in protein quality control1,2and dynamic Ca2+storage3,4in eukaryotic cells. However, the protein homeostasis (proteostasis) system that regulates these ER functions is still incompletely characterised. Previous study revealed the importance of oligomerization in the function PDIA1, an ER-resident disulfide isomerase and molecular chaperone, regulates oligomeric states in accordance with client folding5. This result suggests that at least some of the 20 members of other PDI family may undergo regulated self-assembly in order to optimally function. Here, we show that Ca2+triggers the phase separation of PDIA6 into liquid-like condensates. In contrast to the condensation mechanism observed for proteins containing low-complexity domains, our results indicate that transient but specific electrostatic interactions occur between the first and the third folded thioredoxin-like domains of PDIA6. We further show that the Ca2+-driven condensation of PDIA6 recruits PDIA3 and proinsulin, thus increasing their local concentrations. This process results in the 30-fold enhancement of proinsulin folding and in the inhibition of proinsulin aggregation. Our findings shed light on a condensation-driven Ca2+-mediated proteostasis cascade in the ER by revealing how the efficiency of the protein folding process can be enhanced within quality control granules.
Cryo-EM structures of ρ1 GABAAreceptors with antagonist and agonist drugs
Authors: Fan Chen , Cowgill John , Howard Rebecca J. , Lindahl Erik
Published: July 2024

The family of ρ-type GABAAreceptors includes potential therapeutic targets in several neurological conditions, and features distinctive pharmacology compared to other subtypes. Here we combine structures, recordings and simulations to characterize the binding and conformational impact of the drugs THIP (a non-opioid analgesic), CGP36742 (phosphinic acid inhibitor) and GABOB (an anticonvulsant) on a human ρ1 GABAAreceptor. We identify a distinctive binding pose of THIP in ρ1 versus neuronal α4β3δ GABAAreceptors, offering a rationale for its inverse effects on these subtypes. CGP36742 binding is similar to the canonical ρ-type inhibitor TPMPA, supporting a shared mechanism of action among phosphinic acid inhibitors. Binding of GABOB is similar to that of GABA, but produces a mixture of primed and desensitized states, likely underlying its weaker agonist activity. Together, these results elucidate interactions of a ρ-type GABAAreceptor with therapeutic drugs, offering mechanistic insights and a prospective basis for further pharmaceutical development.
Disruption of CAD oligomerization by pathogenic variants
Authors: Del Caño-Ochoa Francisco , Ramadane-Morchadi Lobna , Eixerés Lluís , Moreno-Morcillo María , Fernández-Leiro Rafael , Ramón-Maiques Santiago
Published: July 2024

CAD is a multi-enzymatic protein essential for initiating the de novo biosynthesis of pyrimidine nucleotides, forming large hexamers whose structure and function are not fully understood. Defects in CAD result in a severe neurometabolic disorder that is challenging to diagnose. We developed a cellular functional assay to identify defective CAD variants, and in this study, we characterized five pathogenic missense mutations in CAD’s dihydroorotase (DHO) and aspartate transcarbamylase (ATC) domains. All mutations impaired enzymatic activities, with two notably disrupting the formation of DHO dimers and ATC trimers. Combining crystal structures and AlphaFold predictions, we modeled the hexameric CAD complex, highlighting the central role of the DHO and ATC domains in its assembly. Our findings provide insight into CAD’s stability, function, and organization, revealing that correct oligomerization of CAD into a supramolecular complex is required for its function in nucleotide synthesis and that mutations affecting this assembly are potentially pathogenic.
Remote sensing of a levitated superconductor with a flux-tunable microwave cavity
Authors: Schmidt Philip , Claessen Remi , Higgins Gerard , Hofer Joachim , Hansen Jannek J. , Asenbaum Peter , Zemlicka Martin , Uhl Kevin , Kleiner Reinhold , Gross Rudolf , Huebl Hans , Trupke Michael , Aspelmeyer Markus
Published: July 2024

We present a cavity-electromechanical system comprising a superconducting quantum interference device which is embedded in a microwave resonator and coupled via a pickup loop to a 6-μg magnetically levitated superconducting sphere. The motion of the sphere in the magnetic trap induces a frequency shift in the SQUID-cavity system. We use microwave spectroscopy to characterize the system, and we demonstrate that the electromechanical interaction is tunable. The measured displacement sensitivity of 10−7m/Hz defines a path towards ground-state cooling of levitated particles with Planck-scale masses at millikelvin environment temperatures.

Published by the American Physical Society
2024
Flux-pulse-assisted readout of a fluxonium qubit
Authors: Stefanski Taryn V. , Andersen Christian Kraglund
Published: July 2024

Much attention has focused on the transmon architecture for large-scale superconducting quantum devices; however, the fluxonium qubit has emerged as a possible successor. With a shunting inductor in parallel to a Josephson junction, the fluxonium offers larger anharmonicity and stronger protection against dielectric loss, leading to higher coherence times as compared to conventional transmon qubits. The interplay between the inductive and Josephson energy potentials of the fluxonium qubit leads to a rich dispersive-shift landscape when tuning the external flux. Here, we propose to exploit the features in the dispersive shift to improve qubit readout. Specifically, we report on theoretical simulations showing improved readout times and error rates by performing the readout at a flux-bias point with large dispersive shift. We expand the scheme to include different error channels and show that with an integration time of 155 ns, flux-pulse-assisted readout offers about a 5-times improvement in the signal-to-noise ratio. Moreover, we show that the performance improvement persists in the presence of finite measurement efficiency combined with quasistatic flux noise and also when considering the increased Purcell rate at the flux-pulse-assisted readout point. We suggest a set of reasonable energy parameters for the fluxonium architecture that will allow for the implementation of our proposed flux-pulse-assisted readout scheme.

Published by the American Physical Society
2024
Consumer sovereignty: a systematic literature review
Authors: Borna Shaheen , Elhajjar Samer , Gu Qiannong
Published: July 2024

Purpose

The purpose of this study is to systematically review the existing literature on the concept of consumer sovereignty.

Design/methodology/approach

By leveraging a systematic literature review using a data-driven approach and quantitative methodology, this study provides an overview of the intellectual structure of consumer sovereignty research.

Findings

We explored the main topics that researchers tackled in consumer sovereignty research. Furthermore, we identified the theoretical lenses used in these studies. Finally, we proposed a research agenda to advance the scholarly debate on consumer sovereignty.

Research limitations/implications

Some limitations should be acknowledged. First, the study only studied and analyzed consumer sovereignty articles that were published in peer-reviewed academic journals. Second, our review comprised journals identified in Scopus. Third, in this study, we have taken into account only articles written in English.

Practical implications

The authors expect the current review to significantly impact the identification of theories for the main trends in the academic analysis of consumer sovereignty and consumer behavior.

Originality/value

This study is the first to provide an integrated view of the body of consumer sovereignty. This review provides a strong contribution to consumer sovereignty literature by recommending a new research agenda for the concept of consumer sovereignty.
Gamify with caution – a three-pronged model to alleviate the dark side of gamification in learning and development
Authors: Singh Swati
Published: July 2024

Purpose

The primary objective of this study is to highlight the three important aspects of effective gamification at work. The three-pronged model discussed in the study provides an opportunity to adopt a more balanced view of gamification and its use rather than just following the hype and trend concerning it.

Design/methodology/approach

While there is promising growth in the adoption of gamification in different L&D processes, the issue of the dark side of gamification cannot be ignored. This article approaches the issue with the help of a three-pronged model. This model has been developed after the review of recent studies focusing on the use of gamification in training and L&D process.

Findings

Gamification can be highly effective in engaging the upcoming generation of employees who are digital natives. However, managers should use gamification with caution. The three-pronged model discussed above can be used to evaluate the effectiveness of gamification for Learning and Development processes. The model provides a balanced view for the use of gamification. The essence of the model is to use gamification to enhance the L&D process and outcome along with enhancing employee motivation and engagement. It is vital to understand that it is a tool and its effectiveness depends upon its right use, by the right person, at the right place and time.

Originality/value

While there is promising growth in the adoption of gamification in different L&D processes, the issue of the dark side of gamification cannot be ignored. This article approaches the issue with the help of a three-pronged model.
The coevolution of corporate capabilities in intellectual property management and technological innovation
Authors: Saksupapchon Punyapat , Willoughby Kelvin W. , Scott Alistair F.
Published: July 2024

Purpose

In this study, we investigate how capability in managing intellectual property may be treated as a type of “dynamic capability,” and we seek to understand how, when it is linked to the new technology development capability of a complex technological organization, these two types of dynamic capabilities may coevolve.

Design/methodology/approach

We conducted a longitudinal empirical case study of Airbus, incorporating an abductive research methodology that required investigating theory and empirical data concurrently and iteratively. The data, ranging over a period of two decades from 2000 to 2021, was collected from four different sources, including interviews, internal company documents, publicly available information and patent data.

Findings

Our main findings are that the capabilities and roles of the Intellectual Property function in Airbus and their interaction with the company's Technology function have indeed influenced the overall innovation strategy of the organization, and that three coevolutionary phases may be identified in the interactive development of the two functions.

Research limitations/implications

Our investigation into how new technology development and intellectual property (IP) management capabilities coevolve within complex technological organizations, exemplified by Airbus, provides significant theoretical and practical implications. Theoretically, it enhances understanding of capability co-development dynamics in complex organizations, particularly in strategic IP management. Practically, it suggests aligning IP strategy with overall corporate objectives and optimizing organizational structures to promote collaboration and efficiency across IP and technology teams. This alignment may foster innovation, maximize the value of intellectual assets and strengthen collaborations, positioning organizations for long-term success in competitive landscapes.

Originality/value

This study makes a fresh contribution to the innovation studies literature by showing how if intellectual property management is treated as a core function of a complex technological organization – rather than simply as a vehicle for protecting new inventions and products after the fact or simply as a constituent part of the organization's legal function – it may contribute proactively to the organization's technological innovation performance. We also address the current gap in the academic literature for a clear understanding of the processes by which different function-specific dynamic capabilities may coevolve in a complex organization operating as part of a dynamic and complex adaptive system.
Navigating the AI horizon in hospitality: a novel classification and future research agenda
Authors: Pan Tianyu , Fu Rachel J.C.
Published: July 2024

Purpose

This study aims to evaluate Artificial Intelligence (AI) research in the hospitality industry based on the service AI framework (mechanical-thinking-feeling) and highlight prospective avenues for future inquiry in this growing domain.

Design/methodology/approach

This paper conceptualizes timely concepts supported by research spanning multiple domains.

Findings

This research introduces a novel classification for the domain of AI hospitality research. This classification encompasses prediction and pattern recognition, computer vision, NLP, behavioral research, and synthetic data generation. Based on this classification, this study identifies and elaborates upon five emerging research topics, each linked to a corresponding set of research questions. These focal points encompass the realms of interpretable AI, controllable AI, AI ethics, collaborative AI, and synthetic data generation.

Originality/value

This viewpoint provides a foundational framework and a directional compass for future research in AI within the hospitality industry. It pushes the industry forward with a balanced approach to leveraging AI to augment human potential and enrich customer experiences. Both the classification and the research agenda would contribute to the body of knowledge that will guide the industry toward a future where technology and human service coalesce to create unparalleled value for all stakeholders.
A capability assessment model for implementing digital technologies in Nigerian heavy construction firms
Authors: Oke Ayodeji Emmanuel , Aliu John , Farhana Mohd Zaini , Jesudaju Oluwatayo Timothy , Lee Hoong-Pin
Published: July 2024

Purpose

Due to the critical importance of digital transformation in enhancing industrial growth and competitiveness, especially in heavy construction, this study introduces a tailored capability assessment model and self-appraisal tool for firms in this sector. These resources enable them to gauge their readiness for adopting digital technology effectively.

Design/methodology/approach

Utilizing the Technology—Organization—Environment (TOE) and Natural Resource Dependence Theory (NRDT) frameworks, 22 markers were identified to structure a questionnaire distributed to construction professionals. Descriptive analysis and fuzzy synthetic evaluation (FSE) were used to develop the capability assessment model. A validation survey assessed the validity of both the model and the self-appraisal instrument.

Findings

The study identified the top five significant markers: (1) leadership commitment to digital transformation, (2) workforce readiness for technology integration, (3) potential ROI through efficiency gains, (4) technology maturity for construction applications and (5) complexity of integrating new technologies with existing workflows. Through FSE, the most critical factors were technology-related, organizational and resource optimization markers.

Originality/value

By employing the TOE and NRDT frameworks, the study identifies the most critical factors influencing digital adoption in heavy construction. Also, the user-friendly self-appraisal instrument developed in this study can be considered a valuable contribution, as it provides heavy construction firms with a practical tool for ongoing monitoring and improvement of their digital transformation efforts.
Ideological Constitutionalism
Authors: Duke George
Published: July 2024

A renewed interest in the concept of ideology is evident in recent constitutional theory. Ideology has featured prominently not only in restatements of traditional Marxist positions and attempted retrievals of the material conception of the constitution, but also in democratic critiques of liberal constitutionalism and theories of constitutional identity. The intention of this article is twofold. Firstly, the article defends the explanatory power of a conception of constitutional ideology that is centred on political domination and the ‘universalisation’ of contingent power relations, rather than more diffuse notions like the symbolic construction of reality or worldviews. Secondly, the article considers distinctive ideological dimensions of modern constitutionalism. An analysis of these dimensions, I contend, confirms modern constitutionalism's strong ideological ‘potential’.
A novel technique for estimating age and demography of long‐lived seabirds (genus Pterodroma) using an epigenetic clock for Gould's petrel (Pterodroma leucoptera)
Authors: Roman Lauren , Mayne Benjamin , Anderson Chloe , Kim Yuna , O'Dwyer Terence , Carlile Nicholas
Published: July 2024

Understanding the demography of wildlife populations is a key component for ecological research, and where necessary, supporting the conservation and management of long‐lived animals. However, many animals lack phenological changes with which to determine individual age; therefore, gathering this fundamental information presents difficulties. More so for species that are rare, highly mobile, migratory and those that reside in inaccessible habitats. Until recently, the primary method to measure demography is through labour intensive mark‐recapture approaches, necessitating decades of effort for long‐lived species. Gadfly petrels (genus: Pterodroma) are one such taxa that are overrepresented with threatened and declining species, and for which numerous aspects of their ecology present challenges for research, monitoring and recovery efforts. To overcome some of these challenges, we developed the first DNA methylation (DNAm) demography technique to estimate the age of petrels, using the epigenetic clock of Gould's petrels (Pterodroma leucoptera). We collected reference blood samples from known‐aged Gould's petrels at a long‐term monitored population on Cabbage Tree Island, Australia. Epigenetic ages were successfully estimated for 121 individuals ranging in age from zero (fledgling) to 30 years of age, showing a mean error of 2.24 ± 0.17 years between the estimated and real age across the population. This is the first development of an epigenetic clock using multiplex PCR sequencing in a bird. This method enables demography to be measured with relative accuracy in a single sampling trip. This technique can provide information for emerging demographic risks that can mask declines in long‐lived seabird populations and be applied to other Pterodroma populations.
Testicular ultrasonographic features predict future risk for bilateral testicular germ cell tumour: A long‐term single centre follow‐up study
Authors: Tenuta Marta , Mazzotta Paola , Sesti Franz , Angelini Francesco , Gelibter Alain J. , Speranza Iolanda , Paoli Donatella , Lombardo Francesco , Anzuini Antonella , Magliocca Fabio Massimo , Franco Giorgio , Cortesi Enrico , Santini Daniele , Lenzi Andrea , Gianfrilli Daniele , Isidori Andrea M. , Pozza Carlotta
Published: July 2024

Background

Bilateral testicular germ cell tumours (B‐GCT) are rare, with an incidence of 2–5%, and can be classified as synchronous (sB‐GCT) or metachronous (mB‐GCT). Our study aimed to identify clinical, biochemical, and radiological risk factors for mB‐GCT in a cohort of patients with GCT at a single tertiary referral centre.

Methods

This retrospective case‐control study included patients with GCT referred to Policlinico Umberto I—Sapienza University of Rome, from 2005 to 2023. We evaluated clinical history, testicular ultrasound features, hormone levels, semen analysis, histological characteristics, staging, and treatments. mB‐GCTs were compared with unilateral GCT patients with a follow‐up longer than the median time‐to‐onset of the second tumour.

Results

Of 319 patients, 52 experienced B‐GCT, with a median time‐to‐onset of the second tumour of 62 months (range: 8–229). The mB‐GCT group showed higher gonadotropin levels (FSH 13.6mUI/mL vs. 7.4mUI/mL, p < 0.001; LH 6.6mUI/mL vs. 3.9mUI/mL, p = 0.004), lower sperm concentration (27 × 106/ejaculate vs. 78 × 106/ejaculate, p = 0.009), smaller residual testis volume (10.4 mL vs. 16.3 mL, p < 0.001), more inhomogeneous echotexture [57.5% vs. 14%, p < 0.001], and presence of microlithiasis (75% vs. 19.5%, p < 0.001). Kaplan–Meier curves confirmed that ultrasound features of the residual testis increased the cumulative risk of developing a second tumour. Microlithiasis was a strong independent predictor (OR 30.712, 95% CI 3.357–280.942, p = 0.002).

Conclusions

Histological features of the first tumour or its treatment do not influence the onset of a second tumour. However, low residual testis volume, inhomogeneous echotexture, and microlithiasis significantly increase this risk. A comprehensive evaluation of the residual testis at baseline is essential for developing a personalised surveillance programme in GCT survivors, with regular ultrasound follow‐up recommended beyond the conventional 5‐year limit.
Design and simulation of a microfluidics‐based artificial glomerular ultrafiltration unit to reduce cell‐induced fouling
Authors: Saud Bhagyashree , Guha Koushik , Iannacci Jacopo , Selishchev Sergei , Sengupta Pratim , Dutta Arindam
Published: July 2024

Background

The microfluidic‐based Glomerulus‐on‐Chips (GoC) are mostly cell based, that is, 3D cell culture techniques are used to culture glomerular cells in order to mimic glomerular ultrafiltration. These chips require high maintenance to keep cell viability intact. There have been some approaches to build non‐cell‐based GoCs but many of these approaches have the drawback of membrane fouling. This article presents a structural design and simulation study of a dialysate free microfluidic channel for replicating the function of the human glomerular filtration barrier. The key advancement of the current work is addressing the fouling issue by combining a pre‐filter to eliminate cellular components and performing filtration on the blood plasma.

Methods

The Laminar Flow Mixture Model in COMSOL Multiphysics 5.6 has been utilized to simulate the behavior of blood flow in the microchannels. The geometrical effect of microchannels on the separation of the filtrate was investigated. The velocity at the inlet of the microchannel and pore size of the filtration membrane are varied to see the change in outflow and filtration fraction.

Results

The efficiency of the device is calculated in terms of the filtration fraction (FF%) formed. Simulation results show that the filtrate obtained is ~20% of the plasma flow rate in the channel, which resembles the glomerular filtration fraction.

Conclusion

Given that it is not dependent on the functionality of grown cells, the proposed device is anticipated to have a longer lifespan due to its non‐cell‐based design. The device's cost can be reduced by avoiding cell cultivation inside of it. It can be integrated as a glomerular functional unit with other units of kidney model to build a fully developed artificial kidney.
Pharmacogenetics in Oncology: A useful tool for individualizing drug therapy
Authors: Nogueiras‐Álvarez Rita , Pérez Francisco Inés
Published: July 2024

With the continuous development of genetics in healthcare, there has been a significant contribution to the development of precision medicine, which is ultimately aimed at improving the care of patients. Generally, drug treatments used in Oncology are characterized by a narrow therapeutic range and by their potential toxicity. Knowledge of pharmacogenomics and pharmacogenetics can be very useful in the area of Oncology, as they constitute additional tools that can help to individualize patients' treatment. This work includes a description of some genes that have been revealed to be useful in the field of Oncology, as they play a role in drug prescription and in the prediction of treatment response.
Establishing the capacity to monitor proteins relevant to the study of drug exposure and response using liver‐derived extracellular vesicles
Authors: Newman Lauren A. , Useckaite Zivile , Wu Ting , Sorich Michael J. , Rowland Andrew
Published: July 2024

Aims

Drug exposure and response is determined by pharmacokinetic (PK) and pharmacodynamic (PD) profiles. Interindividual differences in abundance of drug metabolizing enzymes (DMEs) and drug target proteins underpin PK and PD variability and impact treatment efficacy and tolerability. Extracellular vesicles (EVs) carry protein cargo inherited from originating cells and may be useful for defining differences in key proteins related to hepatic drug metabolism and the treatment of metabolic‐associated fatty liver disease (MAFLD). We sought to quantify these proteins in liver‐derived EVs and establish the profile relative to paired tissue.

Methods

EVs were recovered from human liver tissue samples (LT‐EV, n = 11). Targeted liquid chromatography with tandem mass spectrometry (LC–MS/MS) assays were employed for absolute quantification of proteins in EV isolates and matched liver tissue.

Results

DMEs and MAFLD drug targets were readily detected and quantified in LT‐EVs. Twelve of 15 DMEs exhibited moderate to strong correlation (Spearman ⍴ = 0.618–0.973) between tissue and EVs. Correlation in protein abundance was influenced by the extent of extra‐hepatic expression of the target.

Conclusions

This study provides evidence that key proteins related to PK and PD profiles can be measured in liver‐derived EVs and abundance of liver‐enriched DMEs are robustly correlated between paired tissue and EVs. The robust detection of protein markers related to drug PD profile in MAFLD opens the possibility to track within‐subject changes in MAFLD and lays the foundation for future development of a liver‐derived EV liquid biopsy to assess markers of drug exposure and response in vivo.
Police‐issued barring notices in Western Australia: An analysis of the type, seriousness and trajectory of associated offences
Authors: Farmer Clare , Taylor Nicholas , Baldwin Ryan , Miller Peter G.
Published: July 2024

Introduction

Police‐issued barring notices are currently used in Western Australia in response to alcohol‐related disorderly and anti‐social behaviour. This paper examines the type, severity and trajectory of the offending behaviours associated with served barring notices.

Method

WA Police Force de‐identified the data for 3815 individuals who had received one or more police‐imposed barring notice/s between 2011 and 2020. The offence category associated with each barring notice was examined to explore the overall breakdown and whether/how offending categories change for recipients of subsequent barring notices.

Results

For single and multiple barring notice recipients, the most common offence categories were fighting/physical violence and public order offences. Within a subset of the data, non‐anti‐social offences also spiked. Aggressive behaviours predominate for recipients in metropolitan areas, compared with public order offences in regional locations.

Discussion and Conclusions

For recipients of multiple barring notices, behaviours do not become more serious but neither do they moderate to any notable extent. The low number of repeat barring notices (5%) may suggest an overall beneficial effect on recipient behaviours but more analysis is needed to examine the potential confounding effects of factors, such as fly‐in/fly‐out workers, policing and locational differences.
Fenofibrate and risk of end‐stage renal disease: A nationwide cohort study
Authors: Hyun Young Youl , Kim Kyung‐Soo , Hong Sangmo , Han Kyungdo , Park Cheol‐Young
Published: July 2024

Aim

Previous studies have shown that fenofibrate improves outcomes such as albuminuria and estimated glomerular filtration rate decline. We hypothesize that fenofibrate has renoprotective effects and prevents or delays the development of end‐stage renal disease. The objective of this study is to investigate the risk of incident end‐stage renal disease in relation to fenofibrate treatment in patients who are already taking statins.

Materials and Methods

We performed a nationwide population‐based cohort study using data from the Korea National Health Information Database from 2010 to 2017. Among adults using statins, 413 715 fenofibrate users were compared with 413 715 fenofibrate non‐users after 1:1 age, sex and triglyceride matching. The endpoint of this study was incident end‐stage renal disease.

Results

During a median 3.96‐year follow‐up, the incidence per 1000 person years of end‐stage renal disease was lower in fenofibrate users than in fenofibrate non‐users (0.885 vs. 0.960, p < 0.0001). The hazard ratio for end‐stage renal disease was lower (0.763, 95% confidence interval 0.710–0.821) in fenofibrate users. This association was significant in patients with hypertension, proteinuria and an estimated glomerular filtration rate <60 mL/min/1.732.

Conclusions

Fenofibrate use in patients taking statins with either hypertension, proteinuria, or decreased estimated glomerular filtration rate is associated with a low risk of incident end‐stage renal disease. To confirm the renoprotective effect of fenofibrate in chronic kidney disease, a randomized controlled trial is warranted.
Enhancing equity, diversity and inclusion in the European Union military schools and academies through collaborative initiatives and gender policy reform
Authors: Reis João , Machado Paulo , Dragomir Isabela‐Anda , Malheiro Luís , Rosado David Pascoal
Published: July 2024

The European Union Military Schools and Academies (EUMSAs) have long grappled with persistent gender imbalances among their student body, indicative of an entrenched male‐centric culture within these institutions. In recognition of this issue, the collaborative Military Gender Studies initiative was launched under the auspices of the Erasmus+ program. This project involved partners from Bulgaria, Italy, Portugal and Romania, each offering unique insights shaped by their diverse socio‐political contexts. This research aims to go beyond mere acknowledgment of disparities and instead seeks to identify actionable strategies that can foster genuine equity, diversity and inclusivity within the EUMSAs. To this end, a comprehensive data‐gathering approach was employed, incorporating various qualitative methods including face‐to‐face interviews, face‐to‐face focus groups, direct observations and analysis of official documentation sourced from the referred EUMSAs. The resulting insights highlight the need for substantial improvements in institutional gender policies. Particularly, while efforts have been made to instill gender sensitivity within fitness assessments, their impact has been disappointingly limited. Furthermore, the practice of assigning military roles based solely on gender has been found to undermine both effectiveness and fairness within the schools/academies. Conversely, an encouraging sentiment pervades among the student body, advocating for a curriculum that incorporates gender‐related subjects into the EUMSA educational framework (curriculum). This suggests a growing recognition of the importance of addressing gender issues not only in policy but also in practice, signalling a promising shift towards a more inclusive and equitable environment within the EUMSAs.
Professional dental care and survival rates in long‐term care recipients: A cohort study of 1 459 163 individuals in South Korea
Authors: Ko Kyung‐A , Lee Bo‐A , Kim Young‐Taek , Lee Jung‐Seok
Published: July 2024

Objectives

To determine the dental care pattern and survival rates of participants who received long‐term care (LTC) and a matched control cohort in South Korea.

Background

Global ageing trends and the development of superaged societies pose healthcare challenges. South Korea's LTC system aids those with chronic illnesses and disabilities. Despite the link between oral health and systemic diseases, providing dental care in LTC facilities often reflects social neglect.

Methods

We identified 1 459 163 individuals eligible for LTC insurance in the Korean National Health Insurance Service database from July 2008 to 2015 (LTC cohort) and 1 459 544 individuals matched through propensity‐score matching (matched cohort). The LTC recipients were further categorised into subgroups based on their care type (institutional, home or mixed care). Population of utilising dental services and the average number of dental visits were counted in each cohort, and the survival rate of the LTC cohort was determined according to dental utilisation.

Results

Population of utilising dental services increased steadily in all cohorts except for institutional care, with the highest utilisation (around 30%) observed in the matched cohort. Lower independence in LTC cohorts was associated with lower dental utilisation: 18‐27% for home care, 12‐18% for mixed care, and 10% for institutional care. The survival rates in the LTC cohort were significantly lower than in the matched cohort (P < .0001), with 28.1% survival in LTC vs 59.3% in the matched cohort.

Conclusion

Long‐term care recipients experience social neglect for oral care, while higher survival rates were observed in those utilised dental services.
Flexible modeling of headache frequency fluctuations in migraine with hidden Markov models
Authors: Dumkrieger Gina M. , Ishii Ryotaro , Goadsby Peter J.
Published: July 2024

Objective

To explore hidden Markov models (HMMs) as an approach for defining clinically meaningful headache‐frequency‐based groups in migraine.

Background

Monthly headache frequency in patients with migraine is known to vary over time. This variation has not been completely characterized and is not well accounted for in the classification of individuals as having chronic or episodic migraine, a diagnosis with potentially significant impacts on the individual. This study investigated variation in reported headache frequency in a migraine population and proposed a model for classifying individuals by frequency while accounting for natural variation.

Methods

The American Registry for Migraine Research (ARMR) was a longitudinal multisite study of United States adults with migraine. Study participants completed quarterly questionnaires and daily headache diaries. A series of HMMs were fit to monthly headache frequency data calculated from the diary data of ARMR.

Results

Changes in monthly headache frequency tended to be small, with 47% of transitions resulting in a change of 0 or 1 day. A substantial portion (24%) of months reflected daily headache with individuals ever reporting daily headache likely to consistently report daily headache. An HMM with four states with mean monthly headache frequency emissions of 3.52 (95% Prediction Interval [PI] 0–8), 10.10 (95% PI 4–17), 20.29 (95% PI 12–28), and constant 28 days/month had the best fit of the models tested. Of sequential month‐to‐month headache frequency transitions, 12% were across the 15‐headache days chronic migraine cutoff. Under the HMM, 38.7% of those transitions involved a change in the HMM state, and the remaining 61.3% of the time, a change in chronic migraine classification was not accompanied by a change in the HMM state.

Conclusion

A divide between the second and third states of this model aligns most strongly with the current episodic/chronic distinction, although there is a meaningful overlap between the states that supports the need for flexibility. An HMM has appealing properties for classifying individuals according to their headache frequency while accounting for natural variation in frequency. This empirically derived model may provide an informative classification approach that is more stable than the use of a single cutoff value.
Experiences of older people with multimorbidity regarding self‐management of diseases: A systematic review and qualitative meta‐synthesis
Authors: Tian Jing , Wang Hong Yan , Peng Si Han , Tao Yan Min , Cao Jun , Zhang Xian Geng
Published: July 2024

Aim

This qualitative systematic review aimed to consolidate existing evidence on the self‐management experience of older patients with multimorbidity worldwide.

Methods

Nine databases were searched, for papers published from database inception to April 2023. The systematic review was conducted according to the systematic review method of qualitative evidence by the Joanna Briggs Institute (JBI).

Results

Seven studies were included. Finally, four themes and 12 subthemes were formed: (1) physical level: reduced physical function and lack of coordinated care; (2) psychological level: mental state of anxiety and positive attitude towards life; (3) social level: technical support, support from family, support from healthcare workers and support from others; and (4) practical level: economic burden, lifestyle changes, self‐care in daily life and compliance was much lower than expected.

Conclusions

To improve self‐management in older people with multimorbidity, nurses should provide more guidance to patients to improve their self‐management skills, and clinicians should recommend effective self‐management behaviours.
A combined interactive online simulation and face‐to‐face laboratory enable undergraduate student proficiency in hemocytometer use, cell density and viability calculations
Authors: Costabile Maurizio , Bailey Sheree , Denyer Gareth
Published: July 2024

A hemocytometer is a key piece of laboratory equipment typically used in diagnostic and immunology research laboratories to enumerate white blood cells. The accurate quantification of cell density is essential to ensure accurate numbers of cells are added to assays to generate valid data. Hence, learning to correctly use a hemocytometer is a critical skill for all undergraduate immunology students. However, this skill can be challenging to learn because of students’ unfamiliarity with correct cell identification, differentiating viable versus dead cells and mathematical proficiency in calculating cell density and viability. To address these issues, we developed an interactive computer simulation that replicated all aspects of a Neubauer‐style hemocytometer. This simulation was used to teach second‐year undergraduate immunology students before a face‐to‐face (F‐2‐F) laboratory exercise where these skills were applied. Using a mixed methods approach, student performance and feedback were collected on broad aspects of the intervention and its benefits to the F‐2‐F setting. The approach was found to be extremely successful with all measures indicating a significant impact of the virtual hemocytometer on student learning, understanding and confidence. We suggest that integrating an online simulation to teach students the fundamentals of hemocytometer use and calculations is a valuable educational aid for learning this important skill.