bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simulation of Conducted Responses in Microvascular Networks: Role of Gap Junction Current Rectification
Authors: Djurich Sara , Lee Grace V. , Secomb Timothy W. 
Published: February 2025

ABSTRACTObjectiveLocal control of blood flow depends on signaling to arterioles via upstream conducted responses. Here, the objective is to examine how electrical properties of gap junctions between endothelial cells (EC) affect the spread of conducted responses in microvascular networks of the brain cortex, using a theoretical model based on EC electrophysiology.MethodsModeled EC currents are an inward‐rectifying potassium current, a non‐voltage‐dependent potassium current, a leak current, and a gap junction current between adjacent ECs. Effects of varying gap junction conductance are considered, including asymmetric conductance, with higher conductance for forward currents (positive currents from upstream to downstream, based on blood flow direction). The response is initiated by a local increase in extracellular potassium concentration. The model is applied to a 45‐segment synthetic network and a 4881‐segment network from mouse brain cortex.ResultsThe conducted response propagates preferentially to upstream arterioles when the conductance for forward currents is at least 20 times that for backward currents. The response depends strongly on the site of stimulation. With symmetric gap junction conductance, the network acts as a syncytium and the conducted response is dissipated.ConclusionsUpstream propagation of conducted responses may depend on the asymmetric conductance of EC gap junctions.
Interactions between macro‐ and micro‐climate: Effects on phenolic compound production in Nardus stricta at high elevations
Authors: Moreira X. , Durán J. , Rodríguez A. , Cao A. , Correia M. , Serôdio J. , Rodríguez‐Echeverría S. 
Published: February 2025

Abstract
Phenolic compounds are key to plant defence, offering protection as antioxidants, UV shields, and antimicrobials. Their production is largely shaped by environmental conditions. It is believed that plants at lower elevations increase phenolic content to counter herbivory, while those at higher elevations rely on phenolics to manage abiotic stresses, such as climate variability. Microhabitat warming also affects phenolic levels, but responses differ, depending on broader climatic contexts: plants in warmer, lower‐elevation environments show limited adaptability, whereas high‐elevation plants demonstrate greater plasticity. Despite the importance of these environmental interactions, many small‐scale abiotic studies lack sufficient spatial replication across broader gradients like elevation or latitude, while large‐scale studies frequently overlook microscale factors.
This study investigated the effects of macroclimate factors and microhabitat warming on phenolic production in Nardus stricta across five semi‐natural grassland sites (1546–1875 m a.s.l.) in Portugal's Serra da Estrela. Warming was simulated using open‐top chambers over two growing seasons, after which leaf samples were analysed for phenolic compounds, and soil nutrients were measured.
The N. stricta plants at the highest elevation site contained significantly higher leaf flavonoid concentrations. Microhabitat warming led to a significant decrease in flavonoid concentrations, but only at the highest elevation site. These effects occurred independently of soil nutrient levels, suggesting direct thermal effects or stress responses might be involved.
Our findings highlight the complex interactions between macro‐ and microenvironmental factors in shaping plant chemistry, underscoring critical considerations for plant resilience in the face of climate change. This understanding is essential for developing strategies to support plant and ecosystem adaptation to changing climates.
Fossil Capital in the Caribbean: The Toxic Role of “Regulatory Havens” in Climate Change
Authors: Atiles Jose , Whyte David 
Published: February 2025

ABSTRACTSecrecy jurisdictions play a crucial role in the legal framework perpetuating climate change. This paper demonstrates how these jurisdictions sustain the dynamics of climate change by enabling capital accumulation rooted in environmental degradation. A regulatory approach to law and climate change must address the global nature of the legal structure that upholds exploitative and ecocidal social relationships. This paper argues that secrecy jurisdictions are a pivotal yet under‐analyzed element of the global legal architecture that facilitates climate change. It, therefore, proposes the term regulatory havens to describe their purpose more adequately. Our analysis includes a case study of the Caribbean, as this geographical region operates as the epicenter for externalizing legal liabilities and extra‐legal activities that contribute to climate change while also disproportionately suffering its impacts. The paper outlines how the corporate organizational structure prevalent in regulatory havens enable fossil fuel companies to shield themselves from liability, thus allowing them to detoxify fossil fuel assets. It then sets out a typology of “mechanisms of avoidance” that enable fossil fuel companies to secure key commercial advantages and operate under the radar of regulatory constraints. It briefly analyses the need to dismantle regulatory havens as a prerequisite for building a sustainable economy.
Impact of trailing edge damage on nozzle guide vane aerodynamic performance
Authors: Raduev Zelimhan , Jackson Dougal , Chowdhury Nafiz , Povey Thomas 
Published: February 2025

Abstract
In this paper we consider the impact of trailing edge burn-back on the aerodynamic performance of cooled transonic high-pressure nozzle guide vanes. We consider four levels of burn-back ranging from new parts to severely damaged parts. High-fidelity experimental aerodynamic performance data was taken in the Engine Component AeroThermal facility at the University of Oxford, at engine matched conditions of Mach number, Reynolds number, and coolant-to-mainstream pressure ratio. Experimental data are compared to results of computational fluid dynamics simulations to provide further insights into the mechanisms affecting performance. We find that for fixed row pressure ratio, increasing burn-back leads to: both increased loading, and increased forward loading; increased film cooling flow due to re-loading and increased trailing edge flow due to slot area increase; increased overall boundary layer loss; a significant increase in exit secondary kinetic energy associated with newly formed counterrotating vortices at the edges of the burn-back region; and increased variation in exit whirl angle. We quantify these effects and consider implications for whole-life engine performance.
Multicentre cross-sectional study to assess nursing workload in Belgian emergency departments
Authors: Ganty Thomas , Szecel Julien , Diep Anh , Ghuysen Alexandre , Paquay Méryl 
Published: February 2025

BackgroundExcessive workload in emergency departments (ED) negatively affects patient safety, often leading to missed critical tasks due to time constraints. The Workload Assessment of Nurses on Emergency (WANE) scale developed in Belgium offers a detailed measurement of nursing workload, but its complexity makes it hard to use in practice. Our study aims to find a simpler method for assessing nursing workload in EDs.MethodsA multicentre cross-sectional study was performed in four Belgian EDs between September 2022 and March 2023. Nursing workload was assessed using the WANE scale in each hospital, during 4-hour time periods. The associations between WANE scores, and nurses’ subjective workload assessment, number of patients, patient triage levels, post-triage destination area and the Jones Dependency Tool Score were examined employing multiple linear regression models.Results161 nurses, caring for 591 patients, were included. 67% of the variation in ‘direct’ care time could be explained with a model based on triage level and two items of the Jones Dependency Tool (ABC perturbation and mobility). The number of new patients admitted and nurses’ perceived workload were also highly associated with the total nursing care time TNCT. The actual number of patients in the ED at any time explained 78% of the variation in TNCT. Each additional patient increases the TNTC by 45.22 min.ConclusionsSimple indicators might be used to evaluate the nursing care time in Belgian EDs. A retrospective method is suggested, using the total number of patients over a defined period of time. This study reveals a path to a predictive method to calculate the direct care time for each patient with three simple indicators, available from nursing triage stage.
Claudin18.2 expression in gallbladder cancer correlates with immune activation and a favourable prognosis
Authors: Ni Shu-Juan , Wang Xin , Yuan Lin , Dong Hui , Sun Hui , Tan Cong , Cai Xu , Jiang Wenhua , Sheng Weiqi , Xu Midie , Huang Dan 
Published: February 2025

AimsGallbladder carcinoma (GBC) is frequently diagnosed and treated in advanced stages and has a poor prognosis. Recent studies have identified claudin18.2 (CLDN18.2) as a promising target in digestive system cancer. In this study, we aimed to determine the expression of CLDN18.2 and its correlation with clinicopathological characteristics in patients with GBC.MethodsThe expression of CLDN18.2 of 228 patients with GBC was studied via immunohistochemistry. Immunostained samples were evaluated according to the H-score. The samples were divided into low/negative (H-score=0–49) and high/positive (H-score=50–300) expression groups. The correlations between CLDN18.2 and various clinicopathological characteristics, including survival, were assessed. Multiplex immunofluorescence and image acquisition were used to analyse the relationship between CLDN18.2 expression and the immune microenvironment.ResultsThe overall positive CLDN18.2 staining rate was 39.91% (91/228); 137 (60.08%) were given 0 points, 30 (13.15%) were given 1 point, 28 (12.28%) were given 2 points and 33 (14.47%) were given 3 points. Low CLDN18.2 expression was correlated with adverse prognostic factors, including poor differentiation, deep infiltration depth, lymph node metastasis and distant metastasis. High CLDN18.2 expression was associated with better survival. Furthermore, the distribution of immune cell subsets significantly differed between the high and low CLDN18.2 expression groups.ConclusionsThe correlations between the expression of CLDN18.2 and clinicopathological characteristics and prognosis suggest that early-stage patients could benefit more from future anti-CLDN18.2 treatment and that CLDN18.2 may function as a pivotal regulatory molecule in patients with GBC. The underlying mechanism may be related to immune activation caused by high CLDN18.2 expression.
Income in epidemiological research: a guide to measurement and analytical treatment with a case study on mental disorders and mortality
Authors: Ejlskov Linda , Plana-Ripoll Oleguer 
Published: February 2025

BackgroundIncome is one of the most widely used indicators of socioeconomic position in studies of health inequalities. Despite its frequent use, no empirical-driven guidelines exist on how to operationalise and analytically handle income. In this study, we develop straightforward step-by-step graphical guidelines based on a comprehensive comparative examination.MethodsWe followed the entire population aged 30–65 residing in Denmark in 2010 (n=2 699 296) until death, diagnosis of either severe mental disorder or neurotic, stress-related somatoform or depressive disorders, respectively, or censoring. Adjusted HRs were estimated for four tax-reported income measures, examining variations due to the handling of extreme values, income categorisation and reference categories, both overall and stratified by sex.ResultsAcross all income measures and handling strategies, lower baseline incomes were consistently associated with an elevated risk of experiencing adverse health outcomes with reversed patterns at the lowest end of the income spectrum. At these low-income levels, lower income was associated with a steep increase in corresponding household assets, with very high asset values observed at both ends of the income spectrum. Associations varied mainly for the lowest income categories with some differences in these patterns between males and females depending on the handling of extreme values, income categorisation and choice of reference category.ConclusionThe findings indicate a misclassification of financial capability for the lowest tax-reported incomes and emphasise the need for methodological clarity in income-based health research. The step-by-step graphical guidelines, informed by the findings, offer a methodological framework aiming to enhance the precision, comparability and relevance of future studies.
Oligogenic structure of amyotrophic lateral sclerosis has genetic testing, counselling and therapeutic implications
Authors: Iacoangeli Alfredo , Dilliott Allison A , Al Khleifat Ahmad , Andersen Peter M , Başak Nazlı A , Cooper-Knock Johnathan , Corcia Philippe , Couratier Philippe , deCarvalho Mamede , Drory Vivian E , Glass Jonathan D , Gotkine Marc , Lerner Yosef M , Hardiman Orla , Landers John E , McLaughlin Russell L , Pardina Jesus S Mora , Morrison Karen , Pinto Susana , Povedano Monica , Shaw Christopher E , Shaw Pamela J , Silani Vincenzo , Ticozzi Nicola , van Damme Philip , van den Berg Leonard H , Vourc'h Patrick , Weber Markus , Veldink Jan Herman ,   Project MinE ALS Sequencing Consortium, Dobson Richard , Rouleau Guy A , Al-Chalabi Ammar , Farhan Sali M K 
Published: February 2025

BackgroundDespite several studies suggesting a potential oligogenic risk model in amyotrophic lateral sclerosis (ALS), case–control statistical evidence implicating oligogenicity with disease risk or clinical outcomes is limited. Considering its direct clinical and therapeutic implications, we aim to perform a large-scale robust investigation of oligogenicity in ALS risk and in the disease clinical course.MethodsWe leveraged Project MinE genome sequencing datasets (6711 cases and 2391 controls) to identify associations between oligogenicity in known ALS genes and disease risk, as well as clinical outcomes.ResultsIn both the discovery and replication cohorts, we observed that the risk imparted from carrying multiple ALS rare variants was significantly greater than the risk associated with carrying only a single rare variant, both in the presence and absence of variants in the most well-established ALS genes. However, in contrast to risk, the relationships between oligogenicity and ALS clinical outcomes, such as age of onset and survival, did not follow the same pattern.ConclusionsOur findings represent the first large-scale, case–control assessment of oligogenicity in ALS and show that oligogenic events involving known ALS risk genes are relevant for disease risk in ~6% of ALS but not necessarily for disease onset and survival. This must be considered in genetic counselling and testing by ensuring to use comprehensive gene panels even when a pathogenic variant has already been identified. Moreover, in the age of stratified medication and gene therapy, it supports the need for a complete genetic profile for the correct choice of therapy in all ALS patients.
Lifestyle factors associated with benign multiple sclerosis
Authors: Guo Jie , Olsson Tomas , Hillert Jan , Alfredsson Lars , Hedström Anna Karin 
Published: February 2025

BackgroundBenign multiple sclerosis (MS), characterised by minimal disability despite long disease duration, remains poorly understood in terms of its determinants and prognostic implications. While lifestyle factors have been implicated in modifying disease progression, their role in distinguishing benign and non-benign MS remains unclear.MethodsWe conducted a comparative analysis of patients with benign (n=2040) and non-benign MS (n=4283) using data from Swedish nationwide case-control studies with long-term follow-up. Logistic regression models were used to analyse associations between a history of infectious mononucleosis (IM) and lifestyle factors (smoking, body mass index, fish consumption and sun exposure habits) and the likelihood of benign MS. Additionally, Cox regression was used to follow patients with benign MS from the 15-year mark onward, identifying factors associated with the transition to non-benign MS over time.ResultsThe odds of having benign MS were reduced in association with a history of IM (OR 0.54, 95% CI 0.45 to 0.65), adolescent overweight and obesity (OR 0.69, 95% CI 0.56 to 0.85 and 0.46, 95% CI 0.32 to 0.66, respectively) and infrequent fish consumption (OR 0.72, 95% CI 0.60 to 0.88). Similar associations were observed for the risk of transitioning from benign to non-benign MS over time.ConclusionsA history of IM and modifiable lifestyle factors significantly influence the probability of a benign disease course in MS. These findings underscore the potential for targeted lifestyle interventions to improve MS outcomes. Further research is needed to elucidate the mechanisms by which a past IM infection can continue to influence MS progression long after the initial infection.
Accelerated black holes in (2 + 1) dimensions: quasinormal modes and stability
Authors: Fontana R. D. B. , Rincon Angel 
Published: February 2025

Abstract
We investigate the propagation of a scalar field in a

$$(2+1)$$

(
2
+
1
)

-dimensional accelerated black hole, recently revisited in Arenas-Henriquez et al. (J High Energy Phys https://doi.org/10.1007/jhep05(2022)063, 2022). We briefly describe how the conformal configuration renders a trivial scalar perturbation with a rescaling of the field mass. On the contrary, the free scalar field propagation presents an intricate dynamic, whose equation may be reduced through the use of Israel junction conditions and a non-trivial ansatz. In this case, using two different methods we calculate the quasinormal modes of the solution also obtaining unstable field profiles delivered by the linear scalar perturbation to the background geometry. We examine the parameter space of angular eigenvalues of the field and accelerations under which such instabilities occur.
Restoring Vascular Smooth Muscle Cell Mitochondrial Function Attenuates Abdominal Aortic Aneurysm in Mice
Authors: Liu Yaozhong , Yu Minzhi , Wang Huilun , Dorsey Kristen Hong , Cheng Yalun , Zhao Ying , Luo Yonghong , Zhao Guizhen , Zhao Yang , Lu Haocheng , Deng Yongjie , Mu Wenjuan , Liu Hongyu , Wu Xiaokang , Wang Zhenguo , Zhang Jifeng , Chang Lin , Chen Y. Eugene , Schwendman Anna , Guo Yanhong 
Published: February 2025

BACKGROUND:
Abdominal aortic aneurysm (AAA) is a complex vascular pathology without pharmaceutical interventions. This study aimed to evaluate whether restoring vascular smooth muscle cell (VSMC) mitochondrial function could prevent AAA development.

METHODS:

Ang II (angiotensin II)–induced AAA was established in
Ldlr
-deficient mice, and the gene expression profiles in abdominal aortic tissues exhibiting varying degrees of severity were analyzed. Synthetic high-density lipoprotein (sHDL) formulated with Apoa1 mimetic peptide and phospholipids was evaluated for the protective effects on VSMC mitochondria. The therapeutic efficacy of sHDL was further investigated in Ang II–infusion and PPE (porcine pancreatic elastase)-induced AAA models.

RESULTS:

VSMC mitochondrial damage intensified gradually during AAA development, which was confirmed in distinct AAA animal models and human tissues. sHDL accumulated in the aneurysmatic lesions and restored mitochondrial DNA levels and the expression of genes related to oxidative phosphorylation following Ang II infusion. In mouse primary VSMCs, sHDL maintained mitochondrial homeostasis by suppressing the upregulation of DRP1 (dynamin-related protein 1), a protein involved in mitochondrial fission, reducing the generation of reactive oxygen species, preventing the loss of mitochondrial membrane potential, and preserving mitochondrial respiratory capacity. Administration of sHDL decreased Ang II–induced AAA incidence (control versus treatment, 76% versus 40%;
P
<0.05) and maximum aortic diameters. The protective effects of sHDL were further validated in the PPE model, with reductions observed in maximum aortic diameters and aortic mitochondrial DNA loss. Post-Ang II infusion, administration of sHDL improved VSMC mitochondrial function and suppressed aneurysm growth in Apoe-deficient mice. Human AAA is characterized by mitochondrial dysfunction, and liver-derived HDL (high-density lipoprotein) components play a pivotal role in regulating gene expression in aortic tissues.

CONCLUSIONS:
VSMC mitochondrial damage is a pivotal factor in the development of AAA. The utilization of sHDL nanoparticles represents a promising novel therapeutic approach for AAA, aimed at restoring VSMC mitochondrial function.
Cardiovascular Disease in Anabolic Androgenic Steroid Users
Authors: Windfeld-Mathiasen Josefine , Heerfordt Ida M. , Dalhoff Kim Peder , Trærup Andersen Jon , Andersen Michael Asger , Johansson Karl Sebastian , Biering-Sørensen Tor , Olsen Flemming Javier , Horwitz Henrik 
Published: February 2025

BACKGROUND:
Use of anabolic androgenic steroids (AASs) is associated with increased mortality, and case reports have suggested that some of these deaths are due to cardiovascular disease. However, the epidemiology of cardiovascular disease in AAS users is still relatively unexplored. This study aimed to measure the incidence of cardiovascular disease in male AAS users and to compare these rates with those of a cohort from the general population matched by age and sex.

METHODS:
Men sanctioned in an antidoping program for AAS use in Danish fitness centers between 2006 and 2018 were included and matched for age and sex with 50 times as many controls from the general Danish population. The cohort was followed until June 30, 2023. Using the nationwide registries, we obtained information on admissions, prescriptions, educational length, and occupational status for both the AAS users and controls. This study investigated the incidence of acute myocardial infarction, percutaneous coronary intervention, or coronary artery bypass graft, venous thromboembolism, ischemic stroke, arrhythmia, cardiomyopathy, heart failure, and cardiac arrest during the follow-up period.

RESULTS:
During an average of 11 years of follow-up, AAS users (n=1189) demonstrated a significantly higher incidence of several cardiovascular events compared with controls (n=59 450). Correspondingly, AASs were associated with an increased risk of acute myocardial infarction (adjusted hazard ratio [aHR] 3.00 [95% CI, 1.67–5.39]), percutaneous coronary intervention or coronary artery bypass graft (aHR 2.95 [95% CI, 1.68–5.18]), venous thromboembolism (aHR 2.42 [95% CI, 1.54–3.80]), arrhythmias (aHR 2.26 [95% CI, 1.53–3.32]), cardiomyopathy (aHR 8.90 [95% CI, 4.99–15.88]), and heart failure (aHR 3.63 [95% CI, 2.01–6.55]). Due to the limited number of ischemic stroke and cardiac arrest cases among AAS users, these outcomes were not reportable.

CONCLUSIONS:
AAS use is associated with a substantially increased risk of cardiovascular disease in a large cohort with a long follow-up period.