bluuebunny/crossref_metadata_2025 huggingface dataset:
A hypothalamus-brainstem circuit governs the prioritization of safety over essential needs
Authors: Krauth Nathalie , Sach Lara K. , Clemmensen Christoffer , Kiehn Ole
Published: September 2024

Animals continously adapt their behavior to balance survival and fulfilling essential needs. This balancing act involves prioritization of safety over the pursuit of other needs. However, the specific deep brain circuits that regulate safety-seeking behaviors in conjuction with motor circuits remain poorly understood. Here we identify a class of glutamatergic neurons in the lateral hypothalamic area (LHA) that target the midbrain locomotor-promoting pedunculopontine nucleus (PPN). Upon activation, this LHA-PPN pathway orchestrates context-dependent locomotion, prioritizing safety-directed movement over other essential needs such as foraging or mating. Remarkably, the neuronal activity of these circuits correlates directly with safety-seeking behavior. These circuits may respond to both intrinsic and external cues, playing a pivotal role in ensuring survival. Our findings uncover a circuit motif within the lateral hypothalamus that when recruited, prioritizes critical needs through the recruitment of an appropriate motor action.
ADAR1 orchestrates the ZBP1-mediated PANoptosis and heart transplant rejection
Authors: Lu Haitao , Jiang Jifu , Huang Xuyan , Haig Aaron , Gunaratman Lakshman , Jevnikar Anthony M. , Zhang Zhu-Xu
Published: September 2024

Background

PANoptosis is an integrated form of cell death that combines features of pyroptosis, apoptosis, and necroptosis and is regulated by a complex network of signaling proteins. The roles of ADAR1 (adenosine deaminase acting on RNA 1) and RIPK1 (receptor-interacting serine/threonine-protein kinase 1) in orchestrating the ZBP1 (Z-DNA binding protein 1)-RIPK3 complex to mediate PANoptosis is not fully understood, particularly in the context of heart transplantation.

Objective

This study investigated how ADAR1 and RIPK1 coordinate the activation of the ZBP1-RIPK3 complex to mediate PANoptosis and its implications in mouse heart transplantation.

Methods

Using both in vitro and in vivo models, we analyzed the interactions between ADAR1, RIPK1, ZBP1, and RIPK3. We employed western blotting, and siRNA to elucidate the dynamics of these interactions. Additionally, we assessed the impact of ZBP1 on mouse heart transplantation outcomes.

Results

Our studies revealed that ADAR1 regulates the activation of the ZBP1-RIPK3 complex for PANoptosis. The interaction of ADAR1 with ZBP1 protected against Z-DNA-induced cell death by limiting activations of ZBP1 and RIPK3. In mouse heart transplantation study, we found that ZBP1 and its ligand Z-DNA/Z-RNA were significantly increased in the graft post-transplantation. Furthermore, ZBP1 deficiency in the heart graft inhibited cardiac PANoptosis, attenuated acute graft injury, and induced long-term graft survival.

Conclusion

This study elucidates the role of ADAR1 in ZBP1-mediated PANoptosis. Inhibition of ZBP1 can prevent heart graft injury and rejection. Understanding these mechanisms provides valuable insights into the regulation of cell death and may inform the development of novel therapeutic strategies to improve transplant outcomes.
Mitochondrial topoisomerase I (Top1MT) prevents the onset of metabolic dysfunction-associated steatohepatitis (MASH) in mice
Authors: Baechler SA , Saha LK , Factor VM , Chitnis C , Dhall A , Becker D , Marquardt JU , Pommier Y
Published: September 2024

High fat (HF) diet is a major factor in the development of metabolic dysfunction-associated steatotic liver disease (MASLD) and steatohepatis (MASH), and mitochondria have been proposed to play a role in the pathogenesis of HF diet-induced MASH. Because Mitochondrial topoisomerase I (Top1MT) is exclusively present in mitochondria and Top1MT knock-out mice are viable, we were able to assess the role of Top1MT in the development of MASH. We show that after 16 weeks of HF diet, mice lacking Top1MT are prone to the development of severe MASH characterized by liver steatosis, lobular inflammation and hepatocyte damage. Mice lacking Top1MT also show prominent mitochondrial dysfunction, ROS production and mitochondrial DNA (mtDNA) release, accompanied by hepatic inflammation and fibrosis. In summary, our study demonstrates the importance of Top1MT in sustaining hepatocyte functions and suppressing MASH.
Honey bee egg composition changes seasonally and after acute maternal virus infection
Authors: Chapman Abigail , McAfee Alison , Kenzie L. C. C , Magaña Armando Alcazar , Tarpy David R. , Fine Julia D. , Rempel Zoe , Peters Kira , Currie Rob W. , Hoover Shelley E. R. , Foster Leonard J.
Published: September 2024

Honey bee (Apis mellifera) colonies depend on the reproductive output of their queens, which in turn is contingent on the care provided by worker bees. Viral infections in queens can compromise reproductive output, while worker infections can inhibit the successful functioning of a colony and its ability to care for the queen. Transgenerational immune priming (TGIP) occurs when queens transfer immune-related compounds or immune elicitors to their offspring, enhancing the ability of subsequent generations to resist infections. These maternal effects on offspring could positively impact colony health and resilience to viral infections, but little is currently known about TGIP for viruses. In this study, we investigate how viral infections affect the proteomic composition of eggs laid by virus-challenged queens (injected with a mixture of black queen cell virus and deformed wing virus B), both in controlled experimental settings and natural field conditions. Our results showed that virus-challenged queens upregulated immune effectors in their eggs and ovaries. In contrast, naturally infected queens from field surveys did not; there were no significant differences in egg protein, lipid, or metabolite composition related to maternal viral load or ovary size. However, egg collection date strongly influenced egg composition, likely reflecting seasonal variations in pollen resources. These findings highlight that while viral infections can induce transgenerational effects on egg proteomes under short-term experimental conditions, such effects are less apparent in natural settings and can be overshadowed by seasonal and other ecological factors.
Unique Signatures of Highly Constrained Genes Across Publicly Available Genomic Databases
Authors: Schmitz-Abe Klaus , Li Qifei , Greene Sunny , Borrelli Michela , Luo Shiyu , Ramesh Madesh C. , Agrawal Pankaj B.
Published: September 2024

Publicly available genomic databases and genetic constraint scores are crucial in understanding human population variation and the identification of variants that are likely to have a deleterious impact causing human disease. We utilized the one of largest publicly available databases, gnomAD, to determine genes that are highly constrained for only LoF, only missense, and both LoF/missense variants, identified their unique signatures, and explored their causal relationship with human conditions. Those genes were evaluated for unique patterns including their chromosomal location, tissue level expression, gene ontology analysis, and gene family categorization using multiple publicly available databases. Those highly constrained genes associated with human disease, we identified unique patterns of inheritance, protein size, and enrichment in distinct molecular pathways. In addition, we identified a cohort of highly constrained genes that are currently not known to cause human disease, that we suggest will be candidates to pursue as novel disease-associated genes. In summary, these insights not only elucidate biological pathways of highly constrained genes that expand our understanding of critical cellular proteins but also advance research in rare diseases.
Kinesin-8 motors dimerize by folding their proximal tail domain into a compact helical bundle
Authors: Trofimova Daria , Doubleday Caitlin , Hunter Byron , Arevalo Jesus Serrano , Davison Emma , Wen Eric , Munro Kim , Allingham John S.
Published: September 2024

Kinesin-8 motor proteins help align and segregate chromosomes during mitosis by regulating the dynamics of kinetochore-attached microtubules and the length and position of the mitotic spindle. Some kinesin-8 isoforms accomplish these roles by operating as multifunctional mechanoenzymes that can traverse microtubules, accumulate at the microtubule plus-ends, and then remove terminal αβ-tubulin subunits. While these activities are mainly powered by the motor domain, whose unique structure-function relationships have been recently reported, the non-motor tail domain contains integral functional elements that have not been structurally illuminated. Using theCandida albicansKip3 protein as a kinesin-8 model system, we present an X-ray crystal structure and hydrodynamic data showing how the motor domain-proximal segment of the tail directs the assembly of two kinesin-8 polypeptides into a homodimer that forms the stalk of this motor. Unlike the extended coiled coil-forming helices of most other motile kinesin stalks, the proximal tail ofCaKip3 folds into a compact 92 Å-long four-helix bundle that dimerizes. The first and third helices provide most of the surface area for the dimer interface, while the other two helices brace the folded stalk structure. The upper and lower lobules of the helical bundle are separated by a flexible hinge that gives the exterior faces of the stalk slightly different shapes when bent. We propose that these unique characteristics provide structural rigidity to the kinesin-8 stalk, as well as sites for transient interactions with kinesin-8-associated proteins or other regulatory regions of the motor.
Non-random segregation of mitochondria during asymmetric cell division contributes to cell fate divergence in daughter cells
Authors: Segos Ioannis , Van Eeckhoven Jens , Berger Simon , Mishra Nikhil , Lambie Eric J. , Conradt Barbara
Published: September 2024

The non-random segregation of organelles has been proposed to be an intrinsic mechanism that contributes to cell fate divergence during asymmetric cell division; however,in vivoevidence is sparse. Using super-resolution microscopy, we analysed the segregation of organelles during the division of the neuroblast QL.p inC. eleganslarvae. QL.p divides to generate a daughter that survives, QL.pa, and a daughter that dies, QL.pp. We found that mitochondria segregate unequally by density and morphology and that this is dependent on mitochondrial fission and fusion. Furthermore, we found that mitochondrial density in QL.pp correlates with the time it takes QL.pp to die. We propose that low mitochondrial density in QL.pp promotes the cell death fate and ensures that QL.pp dies in a highly reproducible and timely manner. Our results provide the firstin vivoevidence that the non-random segregation of mitochondria can contribute to cell fate divergence during asymmetric cell division.
Design and test of an
X
-band constant gradient structure
Authors: Gao Qiang , Zha Hao , Shi Jiaru , Lin Xiancai , Du Yingchao , Feng Boyuan , Li Hongyu , Deng Heng , Hu Fangjun , Gao Jian , Li Qingzhu , Gu Weihang , Liu Jiayang , Huang Wenhui , Tang Chuanxiang , Chen Huaibi
Published: September 2024

A light source project named very compact inverse Compton scattering gamma-ray source (VIGAS) is under development at Tsinghua University. VIGAS aims to generate monochromatic high-energy gamma rays by colliding 350-MeV electron beams with 400-nm laser photons within a 12-m beamline. To produce a high-energy electron beam in such a compact space, the system consists of an S-band high-brightness injector and six X-band high-gradient accelerating structures. The goal of the X-band structure is to operate at a high gradient of 80  MV/m. Therefore, we adopts the constant gradient traveling wave approach, where the iris from the first cell to the end cell is tapered. The structure has 72 cells, including 70 cells and 2 couplers, so we named it XT72. The frequency of XT72 is selected to 11.424 GHz, and the 2π/3 mode is adopted. In this paper, we present a comprehensive study covering the detailed design, fabrication, rf tuning, and high-power test results of the first XT72. Additionally, we compare the performance of this structure to that of the previous constant impedance structure. Our results demonstrate that the XT72 is capable of operating at an 80−MV/m gradient with a lower breakdown rate. This advancement paves the way for the development of VIGAS project and contributes to the wider application of X-band room-temperature high-gradient structures in compact accelerator facilities.

Published by the American Physical Society
2024
Target-field design of surface permanent magnets
Authors: Hobson Peter J. , Morley Chris , Davis Alister , Smith Thomas , Fromhold Mark
Published: September 2024

We present a target-field approach to analytically design magnetic fields using permanent magnets. We assume that their magnetization is bound to a two-dimensional surface and is composed of a complete basis of surface modes. By posing the Poisson’s equation relating the magnetic scalar potential to the magnetization using Green’s functions, we derive simple integrals that determine the magnetic field generated by each mode. This approach is demonstrated by deriving the governing integrals for optimizing axial magnetization on cylindrical and circular-planar surfaces. We approximate the governing integrals numerically and implement them into a regularized least-squares optimization routine to design permanent magnets that generate uniform axial and transverse target magnetic fields. The resulting uniform axial magnetic field profiles demonstrate more than a tenfold increase in uniformity across equivalent target regions compared to the field generated by an optimally separated axially magnetized pair of rings, as validated using finite element method simulations. We use a simple example to examine how two-dimensional surface magnetization profiles can be emulated using thin three-dimensional volumes and determine how many discrete intervals are required to accurately approximate a continuously varying surface pattern. Magnets designed using our approach may enable higher-quality bias fields for electric machines, nuclear fusion, fundamental physics, magnetic trapping, and beyond.

Published by the American Physical Society
2024
Nonadiabatic nonlinear non-Hermitian quantized pumping
Authors: Ezawa Motohiko , Ishida Natsuko , Ota Yasutomo , Iwamoto Satoshi
Published: September 2024

We analyze a quantized pumping in a nonlinear non-Hermitian photonic system with nonadiabatic driving. The photonic system is made of a waveguide array, where the distances between adjacent waveguides are modulated. It is described by the Su-Schrieffer-Heeger model together with a saturated nonlinear gain term and a linear loss term. A topological interface state between the topological and the trivial phases is stabilized by the combination of a saturated nonlinear gain term and a linear loss term. We study the pumping of the topological interface state. We define the transfer-speed ratio ω/Ω by the ratio of the pumping speed ω of the center of mass of the wave packet to the driving speed Ω of the topological interface. It is quantized topologically as ω/Ω=1 in the adiabatic limit. It remains to be quantized dynamically unless the driving is not too fast even in the nonadiabatic regime. On the other hand, the wave packet collapses and there is no quantized pumping when the driving is too fast. In addition, the stability against disorder is more enhanced by stronger nonlinearity.

Published by the American Physical Society
2024
Stabilizing Remote Entanglement via Waveguide Dissipation
Authors: Shah Parth S. , Yang Frank , Joshi Chaitali , Mirhosseini Mohammad
Published: September 2024

Distributing entanglement between remote sites is integral to quantum networks. Here, we demonstrate the autonomous stabilization of remote entanglement between a pair of noninteracting superconducting qubits connected by an open waveguide on a chip. In this setting, the interplay between a classical continuous drive—supplied through the waveguide—and dissipation into the waveguide stabilizes the qubit pair in a dark state, which, asymptotically, takes the form of a Bell state. We use field-quadrature measurements of the photons emitted to the waveguide to perform quantum state tomography on the stabilized states, where we find a concurrence of 0.504−0.029+0.007 in the optimal setting with a stabilization time constant of 56±4 ns. We examine the imperfections within our system and discuss avenues for enhancing fidelities and achieving scalability in future work. The decoherence-protected steady-state remote entanglement offered via dissipative stabilization may find applications in distributed quantum computing, sensing, and communication.

Published by the American Physical Society
2024
(E)-1-(3,4-Dimethoxyphenyl)-3-(1,3-diphenyl-1H-pyrazol-4-yl)prop-2-en-1-one
Authors: Sung Jiha
Published: September 2024

In the title compound, C26H22N2O3, the dihedral angle between the benzene and pyrazole rings of the chalcone unit is 88.3 (1)°. The pyrazole ring has two attached phenyl rings that form dihedral angles with the pyrazole ring of 22.6 (2) and 40.0 (1)°. In the crystal, pairwise C—H...O hydrogen bonds generate R
2
2(20) inversion dimers.
Top management team heterogeneity and peer effects in investment decision-making: based on the social learning perspective
Authors: Qian Shuai , Wen Yipeng
Published: September 2024

Purpose

The purpose of this paper is to form propositions about the relationship between top management team (TMT) heterogeneity and peer effects in investment decision-making and explore the mediating role of social learning processes.

Design/methodology/approach

To investigate the correlations between TMT heterogeneity and investment peer effects, we considered the TMT heterogeneity category, team process and contextual factors. With a sample of 8,467 firm-year observations from Chinese listed companies, we used the mean linear model and instrumental variable method to empirically examine their relationships. To identify the mediating role of social learning processes, we introduced a social learning model to find out the contextual factors influencing corporate social learning demands from three aspects and subsequently used comparative statics analysis to explore the variations in the main effect under these contextual factors.

Findings

For task-oriented heterogeneity (e.g. functional background, education and tenure heterogeneity), the opposite effects of information elaboration and social categorization processes make it a nonlinear multiplex correlation with investment peer effects. For relation-oriented heterogeneity (e.g. age and gender heterogeneity), the sole effect of social categorization processes leads to a negative linear correlation. Further, we identify the mediating role of social learning processes. In summary, we established a connection from the TMT heterogeneity, to information elaboration theory or social categorization theory, to social learning processes and ultimately to investment peer effects.

Originality/value

The results of this study provide a comprehensive perspective to predict the decision-making outcomes of team heterogeneity and contribute to heterogeneity research and practice.
Influence of coconut and castor oil coating on engine intake non-woven filter performance
Authors: Nallathambi Gobi , Akasaperumal Rajalekshmi , Robert Berly
Published: September 2024

Purpose

This research focuses on the development and characterization of oil-wetted spun-bonded polypropylene (PP) non-woven filters for improved air intake systems in automobiles. The study aims to enhance engine performance, durability, fuel economy and emission reduction by addressing key aspects such as contaminants filtration efficiency, loading capacity, pressure drop, temperature performance and longevity.

Design/methodology/approach

The research methodology involves the utilization of textile fabrics, particularly oil-wetted spun-bonded PP non-woven filters, renowned for their effective particle collection capability from intake air. Experiments were conducted using a Box–Behnken design with three variables – oil concentration, areal density and dust quantity – each at three different levels to establish correlations with the filter’s dust holding capacity (DHC) and pressure drop.

Findings

The findings indicate that immersing particles in oil-coated medium significantly enhances the filter’s DHC. Notably, castor oil as a coating demonstrates remarkable results, with a 97.53% increase in DHC and a high particulate matter filtration efficiency of 94.12%.

Originality/value

This study contributes to the originality of research by emphasizing the importance of oil density in determining the filter’s DHC and filtration efficiency. Furthermore, it highlights the superiority of castor oil over coconut oil-coated filter media, advancing air intake and/or filter systems for automotive engines.
Examining hotel characteristics and facilities influencing customer satisfaction using decision tree analysis
Authors: Pişirgen Ali , Erdoğan Ali Mert , Peker Serhat
Published: September 2024

Purpose

This study aims to identify the key hotel characteristics and facilities that significantly influence customer satisfaction based on Google review scores. By applying decision tree analysis, the research seeks to determine which aspects, such as service quality, hotel facilities and location, play pivotal roles in shaping customer experiences. The objective is to provide professional with practical recommendations to improve service quality and cultivate enduring customer loyalty.

Design/methodology/approach

The research used a data set collected from Hotels.com, featuring various characteristics of 802 hotels in Izmir Province. Decision tree analysis was conducted using Classification and Regression Tree algorithm to explore the relationship between hotel characteristics and facilities with customer satisfaction.

Findings

The analysis revealed that the number of rooms is the primary factor influencing hotel ratings, with proximity to the airport and hotel classification also being significant. Additional factors such as public transportation distance and laundry services were important, while facilities such as ATMs, beach access and spas showed no significant impact on customer satisfaction. These findings emphasize the importance of core facilities and accessibility.

Originality/value

This study contributes to the literature by offering a novel approach, using decision tree analysis to assess hotel customer satisfaction with structured data. It provides practical implications for hotel managers, enabling them to make data-driven improvements to achieve customer satisfaction. The integration rules created by the decision tree model into hotel management systems can enhance operational efficiency and competitive advantage in the hospitality industry.
Exploring metaverse: affordances and risks for potential users
Authors: Bao Xueqi , Yu Jie , Shou Minghuan
Published: September 2024

Purpose

This article aims to develop and validate a theoretical model via survey data to identify the affordances and challenges influencing metaverse adoption. We specifically examine the impact of immersion on users' adoption decisions and identify which affordances predict this immersion. Additionally, this paper assesses the importance of perceived risks in users' decision-making processes regarding future metaverse engagement.

Design/methodology/approach

Using regression models applied to 198 survey responses, we tested our proposed model. To deepen our insights, we also conducted a qualitative analysis.

Findings

The findings confirm that users' perceptions of immersion and perceived risks are critical determinants in adoption decisions. Social presence, influenced by factors such as ubiquity and interoperability, emerges as a key component of immersion. From the qualitative data, we identified two potential strategies to enhance metaverse immersion: technical improvements and offline device-assisted strategies.

Originality/value

Our study contributes to the literature on information systems (IS) adoption and provides practical insights for practitioners on crucial considerations in metaverse design.
Financial instruments with characteristics of equity: outcomes and value relevance
Authors: Flores Eduardo , Fasan Marco
Published: September 2024

Purpose

This study aims to investigate the motivations behind the issuance of financial instruments with characteristics of equity (FICE), economic consequences associated with their issuance and accounting classifications based on a value-relevance approach.

Design/methodology/approach

Using a sample of 169 financial and nonfinancial firms from 10 jurisdictions that adopted International Financial Reporting Standards, the authors use a difference-in-differences econometric approach.

Findings

The findings reveal that FICE issuers are more leveraged companies with higher costs of equity and, in some cases, lower effective tax rates. This evidence corroborates the hypothesis that issuers of FICEs seek to increase their book values of equity (accounting treatment as equity) and, simultaneously, generate deductible expenses for tax purposes (tax treatment as liability).

Practical implications

This finding suggests that market participants do not treat these instruments as regular equity but rather as quasi-equity. The findings suggest that a binary classification of FICE as debt or equity may not be the accounting treatment that best represents the underlying economic substance of these contracts. Furthermore, this study reinforces the IASB indication regarding to increase the FICE disclosure to allow stakeholders to better understand the economic essence of these bonds.

Originality/value

This study assesses the economic outcomes and market evaluation of a specific type of FICE that has not been previously studied, which is similar to the examples provided by the IASB in their materials on the subject.
Corporate governance and firm performance: in Qatari non-financial firms
Authors: Al-Shaer Basel , Aldboush Hassan H.H. , H. Alnajjar Ahmad Hisham
Published: September 2024

Purpose

This paper aims to examine the relationship between corporate governance mechanisms and firm performance in Qatari non-financial firms over a nine-year period, including the period of high uncertainty caused by the COVID-19 pandemic.

Design/methodology/approach

The study uses data from Refinitiv and employs panel data econometric techniques, namely generalized least squares (GLS), to analyze the impact of board characteristics (board size, board meetings, board gender diversity, board-specific skills, board independence), audit committee features (existence of audit committee, audit committee independence), CEO duality and management scores on both accounting and market performance of Qatari firms. Control variables include firm size, age, leverage and industry classifications.

Findings

The findings suggest that board-specific skills positively influence firm performance, while board size and gender diversity exhibit a non-significant impact. Audit committee independence enhances accounting performance but does not significantly affect market performance. Surprisingly, management scores show a significant yet negative impact on certain financial measures, indicating the need for further investigation.

Practical implications

These insights provide valuable guidance for policymakers, investors and corporate leaders, emphasizing the importance of tailored governance practices in Qatar's unique business landscape.

Originality/value

This study provides unique insights into the governance-performance relationship in the context of Qatar, a region with limited existing research. The inclusion of the COVID-19 period adds a contemporary dimension to the analysis, highlighting the resilience and adaptability of corporate governance practices during times of crisis.
The cascading role of leader-induced defensive cognitions and citizenship pressures in navigating employee silence
Authors: Tahir Muhammad Zohaib , Awan Tahir Mumtaz , Mughal Farooq , Waheed Aamer
Published: September 2024

Purpose

The study aims to attain insights into the impact of destructive leadership and citizenship pressures in inducing employee silence through the lens of social exchange and the conservation of resources theory. The research further relies on Friedkin’s attitude-behaviour linkage framework (2010), while taking into account the role of employees’ defensive cognitive evaluations, as against the previously accented emotion-focused explanations.

Design/methodology/approach

In order to corroborate the pertinence and contextual relevance of the framework, a survey-based study was conducted with a purposively selected sample of 133 full-time employees from the systemically important banks. The sample size was determined through an a-priori power analysis using G*Power, and the hypothesized serial mediation model was tested using PLS-SEM in SmartPLS v_4.0.

Findings

The findings accentuate the significance of destructive leadership in navigating employees’ silence directly and serially through continuance commitment and compulsory citizenship behaviours. The study also underlines that rather than being portrayed as unidimensional outcomes centered on attitudes, employee behaviours ought to be considered contingent retorts under attitude-behaviour cascades.

Originality/value

The study contributes to strategic human resource management literature by offering a cognition-based explanation for employees’ silence, taking Pakistan’s cultural and contextual orientation into cognizance. Extending on the attitude-behaviour linkage framework, the study provides that attitudes shaped by defensive cognitive evaluations may concurrently foster involuntary (citizenship) as well as voluntary (silence) behaviours.
Preventing Postpartum Venous Thromboembolism With Low‐Molecular‐Weight Heparin: The PP‐HEP Pilot Randomised Controlled Trial
Authors: Blondon Marc , Claver Marine , Celetta Emilienne , Righini Marc , de Tejada Begoña Martinez
Published: September 2024

Objective

Uncertainty surrounds the risk–benefit of low‐molecular‐weight heparin to prevent postpartum venous thromboembolism (VTE). Data from randomised clinical trials (RCT) are critically needed, but recent feasibility studies in North America yielded low participation rates, with <1 enrolment per month per centre. Our aim was to assess the feasibility of a trial of postpartum short‐term enoxaparin in Europe.

Design

Pragmatic, open‐label pilot randomised controlled trial (RCT).

Setting

Swiss tertiary hospital.

Population

Postpartum women, within 48 h of delivery, deemed at intermediate risk of VTE with at least one major risk factor (morbid obesity, thrombophilia, emergency caesarean section, pre‐eclampsia, preterm delivery, intrauterine growth restriction or systemic peripartum infection) and/or at least two minor risk factors.

Methods

Participants were randomised to enoxaparin 40–60 mg once daily for 10 days or no treatment, with a 90‐day follow‐up.

Main Outcome Measures

Participation rate and study acceptance (randomised participants among women in whom informed consent was sought).

Results

Recruitment was open for 25 weeks in 2022. Among 1504 postpartum women, 480 were eligible and 77 were randomised. The recruitment rate was 3.1 per week (13.3 per month) and the study acceptance was 23.8%. At 3 months, there was no VTE event, but one major, one nonmajor obstetrical bleeding and one surgical site complication, all in the enoxaparin group.

Conclusions

This pilot RCT of postpartum thromboprophylaxis set in Switzerland yielded greater participation rate and acceptance than previous attempts in North America. It calls for a large, international, collaborative trial to guide this important clinical decision.

Trial Registration

ClinicalTrial.gov identifier: NCT05878899 and NCT04153760.
How to Analyze the Practical Relevance of Costing Methods? The Example of Hospital Cost Accounting in France
Authors: Mériade Laurent
Published: September 2024

Analyses of the practical relevance of costing methods are based on a narrow range of evaluative factors, progressively distancing themselves from the technical essence of these methods. This article examines how a better understanding of the foundational technical underpinnings can enrich the analysis of the practical relevance of a costing method. To do this, we draw on interventionist research in a French cancer centre, where the costing method, prescribed and transposed from private management methods, is widely criticized by its users and rarely analyzed in‐depth. From a theoretical point of view, the results of this article propose a model for analyzing the practical relevance of a costing method. By progressively modifying the calculation techniques of this costing method, the application of this model to the costing method studied highlights four criteria for the technical analysis of the practical relevance of this method, two of which have already been identified in the literature (cost traceability and causality), and two of which have not yet been identified (exhaustiveness of cost centres and cost/value articulation). These four criteria represent the characteristics of this method by which any change in its calculation technique also modifies its practical relevance. From a methodological point of view, this article also shows how a better knowledge of the elements of practical relevance of a costing method can facilitate the success of interventionist research in management accounting. To this end, we propose a three‐step interventionist research approach for analyzing the practical relevance of a costing method.
The Mycobacterium tuberculosis Cell Wall: An Alluring Drug Target for Developing Newer Anti‐TB Drugs—A Perspective
Authors: Chauhan Monica , Barot Rahul , Yadav Rasana , Joshi Karan , Mirza Sadaf , Chikhale Rupesh , Srivastava Vijay Kumar , Yadav Mange Ram , Murumkar Prashant R.
Published: September 2024

The Mycobacterium cell wall is a capsule‐like structure comprising of various layers of biomolecules such as mycolic acid, peptidoglycans, and arabinogalactans, which provide the Mycobacteria a sort of cellular shield. Drugs like isoniazid, ethambutol, cycloserine, delamanid, and pretomanid inhibit cell wall synthesis by inhibiting one or the other enzymes involved in cell wall synthesis. Many enzymes present across these layers serve as potential targets for the design and development of newer anti‐TB drugs. Some of these targets are currently being exploited as the most druggable targets like DprE1, InhA, and MmpL3. Many of the anti‐TB agents present in clinical trials inhibit cell wall synthesis. The present article covers a systematic perspective of developing cell wall inhibitors targeting various enzymes involved in cell wall biosynthesis as potential drug candidates for treating Mtb infection.
Compound heterozygosity for two variants in BMP5 in human skeletal dysostosis with atrioventricular septal defect
Authors: Gregersen Pernille Axél , Hammarsjö Anna , Graversen Lise , Brix Nis , Lindelöf Hillevi , Jensen Uffe Birk , Farholt Stense , Rubak Sune , Bjerre Jesper , Piticchio Serena G. , Terkelsen Thorkild , Nishimura Gen , Hellfritzsch Michel Bach , Grigelioniene Giedre
Published: September 2024

The growth and development of the skeleton is regulated by bone morphogenetic proteins of which several are linked to genetic skeletal disorders. So far, no human skeletal malformations have been associated with variants in BMP5. Here, we report a patient with biallelic loss of function variants in BMP5 and a syndromic phenotype including skeletal dysostosis, dysmorphic features, hypermobility, laryngo‐tracheo‐bronchomalacia and atrioventricular septal defect. We discuss the phenotype in relation to the known tissue‐specific expression of Bmp5 and similar morphological abnormalities previously reported in experimental animal models. Our findings suggest a new association between BMP5 variants and a range of developmental anomalies, involving ears, heart and skeleton, thereby increasing understanding of BMP5's role in human development.
Betulin ameliorates neuronal apoptosis and oxidative injury via DJ‐1/Akt/Nrf2 signaling pathway after subarachnoid hemorrhage
Authors: Lu Xiaoyang , Yang Shu , Lu Qixiong , Zhang Yuansheng , Cha Zaihong , Huang Wei , Li Tao
Published: September 2024

Aims

We aimed to resolve the uncertainty as to whether betulin exerted neuroprotection on early brain injury (EBI) caused by subarachnoid hemorrhage (SAH), and to investigate the related molecular mechanisms.

Methods

Bioinformatic analysis was performed to pre‐study the differently expressed genes (DEGs) and the possible signaling pathways. Rat and cellular model of SAH were introduced in this study, and betulin, an activator of DJ‐1 protein, was administered to reveal the effect. Gross assessment regarding mortality, neurofunctions, SAH grade, brain water content (BWC) along with multiple cellular and molecular studies in vivo or/and in vitro such as immunofluorescence (IF) staining, western blot (WB), reactive oxygen species (ROS) assay, and flow cytometry (FCM) were all conducted after SAH induction to verify the protective effect and the relevant mechanisms of DJ‐1 in diverse levels. In addition, MK2206 (selective inhibitor of Akt) and iRNADj‐1 (interfering RNA to Dj‐1) were utilized to confirm the mechanisms of the effect.

Results

The data from our study showed that DJ‐1 protein was moderately expressed in neurons, microglia, and astrocytes; its level in brain tissue elevated and peaked at 24–72 h after SAH induction. Betulin could efficaciously induce the expression of DJ‐1 which in turn activated Akt and Bcl‐2, and anti‐oxidative enzymes SOD2 and HO‐1, functioning to reduce the activation of cleaved caspase‐3 (c‐Casp‐3) and reactive oxygen species (ROS). The induced DJ‐1 could upregulate the expression of Nrf2. However, Akt seemed no direct effect on elevating the expression of Nrf2. DJ‐1 alone could as well activate Akt‐independent antiapoptotic pathway via suppressing the activation of caspase‐8 (Casp‐8).

Conclusions

Betulin which was a potent agonist of DJ‐1 had the ability to induce its expression in brain tissue. DJ‐1 had neuroprotective effect on EBI through comprehensive mechanisms, including facilitating intrinsic and extrinsic antiapoptotic pathway, and reducing oxidative injury by upregulating the expression of redox proteins. Betulin as an inexpensive drug showed the potential for SAH treatment.
The concurrent validity of a portable ultrasound probe for muscle thickness measurements
Authors: Homer Kai A. , Cross Matt R. , Jukic Ivan
Published: September 2024

Ultrasound imaging is extensively used by both practitioners and researchers in assessing muscle thickness (MT); however, its use in the field is constrained by the transportability of stationary devices. New portable ultrasound probes pose as a cost‐effective and transportable alternative for field‐based assessments. This study evaluated the concurrent validity of a portable probe (Lumify) against a laboratory‐based device (Vivid S5) in measuring MT. Eighteen participants (nine males and nine females) visited the laboratory and their MT measurements were collected using each device at five different sites (anterior and posterior arm, anterior and posterior thigh, and posterior lower leg). Bland‐Altman plots (systematic and proportional bias, random error, and 95% limits of agreement), Pearson's product–moment correlation coefficient (r), and paired samples t‐tests with Cohen's d effect sizes (ES) were used to assess the concurrent validity of the Lumify device. Systematic bias was low at all sites ( ≤ 0.11 cm) while proportional bias was detected only at the posterior lower leg (r2 = 0.217 [r = 0.466]). The difference in MT between devices was significant only at the anterior thigh (p < 0.05); however, ES for all sites were considered trivial (ES ≤ 0.131). Linear associations were found between the devices at each site of measurement (r ≥ 0.95). These results highlight that the Lumify probe can be used interchangeably with the Vivid S5 for MT measurements, providing practitioners and researchers with a more cost‐effective and portable alternative for field‐based assessments.
The endless reform process: Realities behind Jordan's political modernization efforts
Authors: Salameh Mohammed Torki Bani , Alakayleh Moath , Emambocus Washad
Published: September 2024

The latest royal committee headed by Samir Al‐Rifai to modernize Jordan's political system is often portrayed as a significant step toward political reform. However, this narrative overestimates the committee's impact and overlooks historical limitations and institutional obstacles to reform in Jordan. This study highlights how political reform initiatives in Jordan can be manipulated to serve the regime's objectives rather than the people's will. Historically, despite public pressure for genuine political reform, the regime's responses have been minimal. Royal committees and initiatives have rarely produced tangible results, serving more to provide the regime with narratives of superficial reform than to achieve real change.
A New Strategy for Adult T‐Cell Leukemia Treatment Targeting Glycogen Synthase Kinase‐3β
Authors: Ishikawa Chie , Mori Naoki
Published: September 2024

Objectives

The role of glycogen synthase kinase (GSK)‐3β in adult T‐cell leukemia (ATL) caused by human T‐cell leukemia virus type 1 (HTLV‐1) is paradoxical and enigmatic. Here, we investigated the role of GSK‐3β and its potential as a therapeutic target for ATL.

Methods

Cell proliferation/survival, cell cycle, apoptosis, and reactive oxygen species (ROS) generation were examined using the WST‐8 assay, flow cytometry, and Hoechst 33342 staining, respectively. Expression of GSK‐3β and cell cycle/death‐related proteins, and survival signals was analyzed using RT‐PCR, immunofluorescence staining, and immunoblotting.

Results

HTLV‐1‐infected T‐cell lines showed nuclear accumulation of GSK‐3β. GSK‐3β knockdown and its inhibition with 9‐ING‐41 and LY2090314 suppressed cell proliferation/survival. 9‐ING‐41 induced G2/M arrest by enhancing the expression of γH2AX, p53, p21, and p27, and suppressing the expression of CDK1, cyclin A/B, and c‐Myc. It induced caspase‐mediated apoptosis by decreasing the expression of Bcl‐xL, Mcl‐1, XIAP, c‐IAP1/2, and survivin, and increasing the expression of Bak and Bax. 9‐ING‐41 also induced ferroptosis and necroptosis, promoted JNK phosphorylation, and suppressed IKKγ and JunB expression. It inhibited the phosphorylation of IκBα, Akt, and STAT3/5, induced ROS production, and reduced glycolysis‐derived lactate levels.

Conclusion

GSK‐3β functions as an oncogene in ATL and could be a potential therapeutic target.
Real‐world effectiveness and safety of switching to dolutegravir/lamivudine among people living with HIV‐1 aged over 50 years who are virologically suppressed
Authors: Piñeiro C. , Policarpo S. , Caldas C. , Santos L. , Augusto I. , DiMondi V. P. , Serrão R.
Published: September 2024

Objectives

People living with HIV face several challenges as they age, including the potential for polypharmacy and increased susceptibility to drug‐related adverse effects. Thus, effective and well‐tolerated regimens with minimal or no drug interactions would be useful in this population. We present real‐world effectiveness and safety data for individuals aged >50 years who achieved virological suppression (HIV‐1 RNA <50 copies/mL) and switched to dolutegravir/lamivudine (DTG/3TC).

Methods

This retrospective, observational, single‐centre study conducted in Portugal included individuals aged >50 years who switched to DTG/3TC while virologically suppressed and had ≥12 months of follow‐up. Proportions of individuals maintaining virological suppression were described at 12 months; CD4+ cell counts were described at baseline and 12 months. Descriptive subgroup analyses were performed based on age, sex assigned at birth, and availability of historical genotypic resistance results.

Results

Overall, 538 individuals aged >50 years were included (74% male; mean age, 62 years; mean time on previous therapy, 160 months). High proportions (intention‐to‐treat population, 97%; on‐treatment population, 98%) of individuals who switched to DTG/3TC maintained virological suppression through 12 months of follow‐up. CD4+ cell counts remained stable (mean baseline: 727 cells/mm3 [range 94–2371]; mean month 12: 742 cells/mm3 [range 99–2659]). No individuals experienced virological failure. Nine (2%) individuals discontinued DTG/3TC for non–treatment‐related reasons. Proportions with virological suppression at month 12 were similar between on‐treatment subgroups by age, sex assigned at birth, and historical genotypic resistance results availability.

Conclusions

DTG/3TC demonstrated robust effectiveness and a good safety profile in individuals aged >50 years with virological suppression in Portugal.
The use of herbs and spices in fish preservation at chilled temperature storage: opportunities and challenges
Authors: Parmar Bhaviksinh K. , Mohite Ashish S. , Pathan Dabir I. , Desai A. S. , Wasave Suhas M.
Published: September 2024

Fish can justify a healthy human diet. Spoilage is caused due to microbial degradation and oxidative rancidity. Herbs and spices (H&S) are common ingredients in fish marination to improve quality and appeal to consumers globally. The given review delves into the potential of H&S to extend the freshness of fish while also addressing challenges in maximising their effectiveness for preservation and proposing innovative solutions. H&S with antimicrobial (AM) and antioxidative (AO) effects reduce biogenic amine (BA) formation by inhibiting the decarboxylation of free amino acids through microbial reduction and retarding lipid oxidation of free fatty acids by countering free radicals. Combining organoleptically standardised H&S with diverse microbial hurdle techniques supports extensive domestic utilisation, extending the shelf life of fish significantly compared to using them alone. The present findings recommend that H&S can maintain fish quality for 6–20 days, depending on the fish species, packaging, and AO/AM potential in refrigeration conditions. Thyme, garlic, ginger, stevia, turmeric, laurel, sage, cinnamon, cumin, mint, and rosemary are found to be the most potent preservatives that could be utilised commercially to increase fish's shelf life. Variations in H&S extracts and fish muscle composition pose challenges in optimising the effectiveness of bioactive compounds in fish preservation. Innovative approaches for utilising H&S essential oils (EOs) and advanced delivery techniques offer solutions to these challenges, leading to improved fish quality and limited shelf life.
Effect of dry aging on quality parameters, protein profile and protein oxidation level of beef
Authors: Savas Adem , Oz Emel , Elbir Zeynep , Oz Fatih
Published: September 2024

The effect of dry aging process (15 and 30 days) on some quality parameters, protein profile and formation of protein oxidation products of beef was investigated. The maximum weight and trim loss were calculated to be 47.07% and 23.06%, respectively. The meat dry‐aged for 30 days had higher dry matter, pH and protein content, but lower L* and a* values than those of the unaged meats. There was a significant decrease in actin protein band density in the meat dry‐aged for 30 days and a new protein band of 32 kDa appeared in the myofibrillar protein fraction. The dry aging process caused an insignificant increase in the total carbonyl content (P > 0.05). However, the γ‐glutamic semialdehyde (GGS), α‐aminoadipic semialdehyde (AAS) and total GGS and AAS contents were higher in the dry‐aged meats for 30 days. Total GGS and AAS contents ranged from 15.36% to 31.87% of the total carbonyl content. It was found that there was no significant difference between control group (unaged) meats and the meat dry‐aged for 15 days in terms of protein oxidation products.