bluuebunny/crossref_metadata_2025_split huggingface dataset:
Three’s a Crowd: Essence, Concept, and Language in Jurisprudential Methodology
Authors: Liu Ziyu 
Published: February 2025

Abstract
This paper evaluates new developments in the debate on essentialism in jurisprudential methodology and contributes to this debate in the following ways: First, it interprets Hillary Nye’s challenge to Razian essentialism as an integration challenge of reconciling the metaphysics of law couched in terms of necessary truths with a proper epistemology to attain those truths. Second, drawing upon Julie Dickson’s recent defense of Razian essentialism and Frank Jackson’s account of conceptual analysis, it argues that Nye’s criticism—which exploits the potential gap between the nature of law and our concept of law—misses the mark, because it conflates two kinds of essentialism. Third, it sheds new light on the relation between Raz’s project of conceptual explanation and Frank Jackson’s project of conceptual analysis, by explaining why the congeniality between these two projects has been overlooked by both sides of the debate on Razian essentialism.
Functional neuroimaging in disorders of consciousness: towards clinical implementation
Authors: Kazazian Karnig , Monti Martin M , Owen Adrian M 
Published: February 2025

Abstract
Functional neuroimaging has provided several new tools for improving both the diagnosis and prognosis in patients with DoC. These tools are now being used to detect residual and covert awareness in behaviourally non-responsive patients with an acquired severe brain injury and predict which patients are likely to recover. Despite endorsement of advanced imaging by multiple clinical bodies, widespread implementation of imaging techniques such as functional MRI (fMRI), electroencephalography (EEG), and positron emission tomography (PET) in both acute and prolonged disorders of consciousness patients has been hindered by perceived costs, technological barriers, and lack of expertise needed to acquire, interpret, and implement these methods. In this review we provide a comprehensive overview of neuroimaging in DoC, the different technical approaches employed (i.e. fMRI, EEG, PET), the imaging paradigms used (active, passive, resting state) and the types of inferences that have been made about residual cortical function based on those paradigms (e.g., perception, awareness, communication). Next, we outline how these barriers might be overcome, discuss which select patients stand to benefit the most from these neuroimaging techniques, and consider when during their clinical trajectory imaging tests are likely to be most useful. Moreover, we make recommendations that will help clinicians decide which advanced imaging technologies and protocols are likely to be most appropriate in any particular clinical case. Finally, we describe how these techniques can be implemented in routine clinical care to augment current clinical tools and outline future directions for the field as a whole.
Could immunotherapy and regulatory T cells be used therapeutically to slow the progression of Alzheimer’s disease?
Authors: Abbott Victoria , Housden Benjamin E , Houldsworth Annwyne 
Published: February 2025

Abstract
Alzheimer’s disease and other cognitive impairments are a growing problem in the healthcare world with the ageing population. There are currently no effective treatments available, however it has been suggested that targeting neuroinflammation may be a successful approach in slowing the progression of neurodegeneration. Reducing the destructive hyperinflammatory pathology to maintain homeostasis in neural tissue is a promising option to consider. This review explores the mechanisms behind neuroinflammation and the effectiveness of immunotherapy in slowing the progression of cognitive decline in Alzheimer’s disease patients. The key components of neuroinflammation in Alzheimer’s disease researched are microglia, astrocytes, cytokines and CD8+ effector T cells. The role of oxidative stress on modulating regulatory T cells and some of the limitations of regulatory T cell-based therapies are also explored. Increasing regulatory T cells can decrease activation of microglia, proinflammatory cytokines and astrocytes, however it can also increase levels of inflammatory cytokines. There is a complex network of regulatory T cell interactions that reduce Alzheimer’s disease pathology which is not fully understood.
Exploring the current literature, further research into the use of immunotherapy in Alzheimer’s disease is vital to determine the potential of these techniques, however there is sufficient evidence to suggest that increasing regulatory T cells count does prevent Alzheimer’s disease symptoms and pathology in Alzheimer’s disease patients. Some exciting innovative therapies are muted to explore in the future. The function of regulatory T cells in the presence of reactive oxygen species, and oxidative stress should be investigated further in patients with neurogenerative disorders to ascertain if combination therapies could reduce oxidative stress while also enhancing regulatory T cells function. Could methods of immunotherapy infuse exogenous functional Tregs or enhance the immune environment in favour of endogenous regulatory T cells differentiation thus reducing neuroinflammation in neurodegenerative pathology, inhibiting the progression of Alzheimer’s disease?
Infective endocarditis with perforation of the anterior mitral valve leaflet due to mild aortic regurgitation: A case report
Authors: Yamanaka Tetsuo , Higashitani Michiaki , Ichinohe Yoshimaro , Fukatsu Toru , Kunihara Takashi 
Published: February 2025

Abstract

Background
It has been reported that mechanical damage occurs when regurgitant flow from aortic regurgitation (AR) directly impinges on the anterior mitral valve leaflet (AML). However, only a few cases of mitral valve perforation have been reported. Previous reports suggest that AR in such cases tends to be grade 3 or higher and that hemodynamic damage to the mitral valve due to AR may be proportional to its severity. On the contrary, no cases of mitral valve perforation due to mild AR have been reported.

Case summary
In 2011, a 56-year-old man presented with mild AR towards the AML, revealed on a transthoracic echocardiogram. In 2016, 3 months before admission, the patient had been experiencing intermittent fevers of over 40 °C, which did not improve, and was referred to our hospital. A detailed examination revealed a vegetation on the AML where the aortic valve was displaced, and the site was perforated. The AR was mild to moderate. Blood cultures were positive for Streptococcus oralis. From these results, a definitive diagnosis of infective endocarditis (IE) was made. The patient had cerebral infarction and underwent semi-emergency surgery.

Discussion
This case indicates that even mild AR directed at the AML can damage the AML, raising IE risk. Consequently, mild AR deviation towards the AML should be considered a potential risk factor for AML IE.
Remnant cholesterol, plasma triglycerides and risk of cardiovascular disease events in young adults: a prospective cohort study
Authors: Aaseth Eirik , Halvorsen Sigrun , Helseth Ragnhild , Gravning Jørgen A 
Published: February 2025

Abstract

Aim
To investigate if elevated levels of cholesterol carried in triglyceride-rich lipoproteins, marked by remnant cholesterol or plasma triglycerides, are associated with increased risk of premature cardiovascular disease (CVD) events in young adults.

Methods
Prospective cohort study. In year 2000, all 30-year-old inhabitants living in Oslo, Norway, were invited to the “Oslo Health Study” including a clinical examination and routine blood tests. Follow-up with respect to CVD events (cardiovascular death, non-fatal myocardial infarction, non-fatal ischemic stroke, coronary revascularization, or hospitalization for unstable angina) was obtained by linkage with national mandatory registries through 2022. We estimated the risk of CVD events in relation to levels of remnant cholesterol and plasma triglycerides at inclusion using Cox regression analysis. The risk of CVD events in relation to LDL cholesterol (LDL-C) levels was estimated as comparison.

Results
A total of 5939 participants were included (median age 31 years, 56% women). During a median follow-up time of 22 years, a CVD event occurred in 107 (1.8%) participants. The adjusted hazard ratio (aHR) for CVD events per 0.5 mmol/L increase in remnant cholesterol concentrations was 1.3 (95% CI: 1.1-1.5). Per 1 mmol increase in plasma triglycerides and LDL-C concentrations, the aHR for CVD events was 1.2 (95% CI: 1.1-1.4) and 1.3 (95% CI: 1.1-1.6), respectively.

Conclusion
Already at 31 years of age, higher concentrations of remnant cholesterol and plasma triglycerides were associated with increased risk of premature CVD events. We suggest that remnant cholesterol or plasma triglycerides are included in the risk assessment of young adults.
Content Hubs, Information Flows, And Reactions for Pesticide-Related Discussions On Twitter
Authors: Zhou Tiancheng , Huang Yu , Avanasi Raghavendhran , Brain Richard A , Prosperi Mattia , Bian Jiang 
Published: February 2025

Abstract
Pesticides are essential in modern agriculture for controlling pests and enhancing food production. However, concerns about their human and environmental health impacts have broadened discussions on their use, regulation, ethics, and sustainability. Scientific research, media coverage, input from corporations, governments, and non-governmental organizations (NGOs) shape public opinions and potentially influence regulatory decisions. This project analyzed pesticide-related discussions on Twitter/X from 2013 to 2022, focusing on information influence and propagation among individuals and organizations, advancing over prior research that looked at topic frequency, trends, and geography. Using a validated snowball sampling method, we collected over 3 million tweets from 1 million users and identified key network influencers, ie, information hubs, analyzing their content, popularity, and characteristics. Machine learning and a tailored information flow score were used to explore the dynamics of information flow and sentiment across hubs. Our analysis revealed that organizational hubs, particularly NGOs and media, were more active and had higher follower-to-following ratios than individual influencers. NGOs and media also dominated the pesticide-related discourse, while individual influencers had a lesser role. Information sources were unevenly distributed, with a dominance of retweets, news, and media posts, and a low prevalence of scientific sources. Information flow was high through NGOs, academia, and individuals, but poor from government accounts. Pesticide-focused hubs were more active and targeted in their information dissemination, with public sentiment largely negative. By delving deeper into the dynamics of information dissemination and influence networks, this study provides insights that emphasize 1) the need for better communication strategies to integrate diverse stakeholder perceptions and values, and 2) prioritizing the dissemination of credible scientific information, while also addressing sectoral disparities. Together, they can help policymakers and industry stakeholders build trust, promote transparency, and advance sustainable pesticide regulation.
Bioavailability and risk assessment of metals in freshwaters: is global regulatory implementation keeping pace with scientific developments?
Authors: Merrington Graham , Gensemer Robert W , Gilron Guy , Wilson Iain , Peters Adam , Van Dam Rick , Golding Lisa A , Stauber Jenny , Gadd Jennifer , Smith Ross , DeForest David , Garman Emily , Middleton Ellizabeth , Ryan Adam , Cooper Christopher A , Smith Erin , Baken Stijn 
Published: February 2025

Abstract
The scientific knowledge that enables the prediction of potential aquatic ecological risks due to exposure of metals based on freshwater chemistry data have been available for several decades. As a result, ecosystems can be protected, using frameworks and procedures incorporated into regulatory approaches. Yet, when evaluating how freshwater risks from metals are assessed globally, it is apparent that regulatory jurisdictions differ in their progress, and approaches, when accounting for bioavailability. It is entirely reasonable and appropriate for there to be a lag in time between the development of the science and its incorporation into routine regulatory environmental protection. We openly acknowledge that this is not just a regulatory challenge and take a more holistic view of the implementation of the science that informs metal bioavailability. Implementation comprises the steps required to utilize science and knowledge to enable its practical, beneficial, and routine application in regulatory decision making. Different regulatory jurisdictions have taken varied approaches to account for metal bioavailability. We have made specific use of frameworks that utilize limit values, such as water quality guidelines, criteria and quality standards, to illustrate the similarities and differences in the implementation of bioavailability. Approaches taken in Europe, Canada, Australia and New Zealand, and the United States were reviewed and evaluated. While some of these approaches, or parts thereof, have been successful, other aspects have been less so. In this evaluation, we have identified key commonly encountered obstacles and challenges in these approaches to the implementation of metal bioavailability. Finally, we provide an evidence-driven ‘road map’ to the successful regulatory implementation of metal bioavailability in risk assessment, drawn from successful components of the approaches reviewed. The application of this framework will enable regulatory jurisdictions to readily keep pace with the science pertaining to metal bioavailability and avoid the challenges experienced by others.
Investigating metrics of discrete-individual repeatability of the stress response
Authors: Beattie Ursula K , Romero L Michael , Reed J Michael 
Published: February 2025

Abstract
There is currently no consensus on the most biologically meaningful way to calculate discrete-individual repeatability of stress response curves. In the current study, we compared three metrics of discrete-individual repeatability that incorporate the whole stress response curve: profile repeatability, Kullback-Leibler (KL) divergence, and hypothalamic-pituitary-adrenal (HPA) flexibility. As part of this work, we present a new R package for computing profile repeatability, “profrep”. Using three datasets (one synthetic and two corticosterone datasets from live birds), our objectives were (1) to compare how these metrics correlate with one another and (2) to determine how representative repeatability scores of fewer replicates were to the “consensus” score (i.e., the score of the full dataset). We found that (1) these three discrete-individual repeatability metrics do not consistently correlate with one another; (2) KL divergence and HPA flexibility are poor at distinguishing individuals from each other, i.e., they give similar scores for each individual regardless of perceived repeatability; and (3) that profile repeatability tends to overestimate repeatability when fewer replicates are available, and the consensus score is low. Despite this drawback of profile repeatability, we suggest that it may be the most well-suited metric for assessing discrete-individual repeatability.
Valuable predictive power of prognostic nutritional index in metastatic breast cancer patients treated with CDK4/6 inhibitors
Authors: Önder Tuğba , Öner İrem , Karaçin Cengiz , Ateş Öztürk 
Published: February 2025

Abstract

Aims and Objectives
The prognostic value of nutritional status in HR+/HER2- metastatic breast cancer (mBC) patients treated with CDK4/6 inhibitors (CDK4/6is) and endocrine therapy (ET) is unclear.

Methods/Materials
The effect of PNI values before starting CDK 4/6i on patient prognosis was retrospectively analyzed.

Results
A total of 431 patients were evaluated. After 35.7 months of follow-up, the median overall survival (mOS) was 46.3 months (95% CI, 29.7–62.8). The PNI-low group had decreased progression-free survival compared to the PNI-high group [16.6 vs. 30.5 months; univariate HR = 1.640, 95% confidence interval (CI): 1.281–2.099, P &lt; .001]. The PNI-low group's mOS was noticeably shorter than the PNI-high group (35.0 months vs. not reached; multivariate-adjusted HR: 2.082, 95% CI: 1.398–3.102, P &lt; .001). When stratified by CDK4/6i line: In patients using CDK4/6i as the first line, mPFS for the PNI-low and PNI-high group was 24.6 vs. 35.6 months (P = .026), and survival probabilities at 24, 36, and 48 months in the PNI-low and PNI-high groups were 75%, 62%, 57%, and 88%, 80%, and 72%, respectively (P = .002). In patients using CDK4/6i as the second line and after, mPFS was 8.2 vs.12.0 months (P = .014), and mOS was 18.6 vs. 39.6 months (P = .001) for the PNI-low and PNI-high group, respectively. The ORR and DCR were significantly lower in the low-PNI group than in the high-PNI group (P = .018 and P = .017, respectively). The incidence of grade 3–4 side effects due to CDK4/6is (39.8% vs. 30.7%, P = .046) was significantly greater in the PNI-low group than in the PNI-high group.

Conclusions
This study's results suggest that PNI is an easily measured and reliable indicator of prognosis in mBC patients treated with CDK4/6i and ET.
Critical Thinking: Stress-testing Competing Reasons in the Practical Domain
Authors: Dunne Gerry 
Published: February 2025

Abstract
Harvey Siegel has argued that successful critical thinking requires both a critical mindset and expertise in evaluating reasons. In this paper, I focus on the latter, the business of accurately appraising competing reasons in the practical domain. More specifically, I critically examine the limitations inherent in two commonly used epistemic frameworks: the balance account and reasons-for-and-against. I argue neither is suitable for scenarios requiring especially nuanced appraisals or complex metrics. This is because they primarily deal with somewhat crude approximations and/or binary choices. I will propose a new framework to address this concern. I dub this the stress-testing-critique-support-explanationist account (STCSEA). STCSEA is engineered to handle complex practical epistemic situations, ones where determining what to do is not straightforward or immediately calculable. To fully understand the accurate and reliable determination of competing reasons’ strengths and weaknesses, educators require sophisticated tools. Such tools can help us fully to grasp the concept and mechanics of rational defeat—that being figuring out the strength of competing reasons. To do so, we must also formulate and continuously refine an operationalized defeasibility taxonomy.
I proceed as follows. In Section 1, I provide a brief overview of the critical thinking debate. I then survey John Pollock’s work on defeaters. This work is germane to the conversation yet remains something of a lacuna in the contemporary philosophy of education literature. In Section II, I discuss the balance account and reasons-for-and-against, specifically their evident limitations. In Section III, I make a case for the superiority of STCSEA when it comes to handling ‘hard cases’. These are cases where what we should, must, or may do, involves a complex computation. Such computations often exceed the mathematical or epistemic resources associated with ‘balancing metaphors’ and ‘for and against’ determinations.
Legal framework for hydrogen production in Austria using the specific example of a company site in Tyrol
Authors: Monsberger Carolin , Thaler Bernhard , Steinlechner Sebastian , Fina Bernadette 
Published: February 2025

Abstract
This article examines the legal framework for hydrogen production in Austria within the broader context of European Union (EU) regulations, focusing on a company site in Tyrol. At the EU level, the Industrial Emissions Directive, the EU Hydrogen Strategy, the REPower EU Plan, and the Delegated Acts to the Renewable Directive are addressed. For the national regulation in Austria, regulations for electrolyzers (e.g. licensing and safety regulations) as well as the regulation of hydrogen networks—or the absence thereof—are examined. The study assesses the impact of these regulations on an operating location in Tyrol. This analysis reveals the intricate legal landscape shaping hydrogen production in the EU and, specifically, in Austria, highlighting challenges for project development and compliance. The study underscores the need for clarity and harmonization in regulations to support the growth of a sustainable hydrogen economy.
Bioremediation potential of Pseudomonas aeruginosa to counteract Arsenite-induced phytotoxicity in Solanum lycopersicum cultivated within a contaminated agroecosystem
Authors: Patel Vivek , Supriya G Naga Rathna 
Published: February 2025

Abstract
Trivalent arsenic (AsIII) is the most toxic form of arsenic, accumulates in plant systems through aquaporins, and inhibiting plant growth. This study focuses on mitigating the bioavailability of arsenite (AsIII) in agricultural soils through biological approaches. A potential AsIII tolerant bacterium Pseudomonas aeruginosa VS3 was isolated from contaminated soil. Subsequent analysis revealed that this strain can produce EPS and biofilms. Additionally, the strain exhibited production of plant growth promoting traits (IAA, gibberellins, and solubilisation of Si). Biotransformation assay demonstrated that strain can oxidize AsIII to the less toxic arsenate (AsV) with conversion efficiency of 51%. Findings from the field trial proven that P. aeruginosa significantly reduced AsIII toxicity in S. lycopersicum and boosted plant growth under AsIII stress conditions. Additionally, inoculation with P. aeruginosa enhanced the activities of antioxidant enzymes (40% increase in peroxidase and a 17% increase in PAL) compared to untreated controls under AsIII stress. The bacterial treatment reduced arsenic accumulation in root tissues, demonstrating P. aeruginosa VS3’s potential as a bioremediation agent to alleviate arsenite stress and enhance plant growth.
RTFAST-Spectra: Emulation of X-ray reverberation mapping for active galactic nuclei
Authors: Ricketts Benjamin J , Huppenkothen Daniela , Lucchini Matteo , Ingram Adam , Mastroserio Guglielmo , Ho Matthew , Wandelt Benjamin 
Published: February 2025

Abstract
Bayesian analysis has begun to be more widely adopted in X-ray spectroscopy, but it has largely been constrained to relatively simple physical models due to limitations in X-ray modelling software and computation time. As a result, Bayesian analysis of numerical models with high physics complexity have remained out of reach. This is a challenge, for example when modelling the X-ray emission of accreting black hole X-ray binaries, where the slow model computations severely limit explorations of parameter space and may bias the inference of astrophysical parameters. Here, we present RTFAST-Spectra: a neural network emulator that acts as a drop in replacement for the spectral portion of the black hole X-ray reverberation model RTDIST. This is the first emulator for the reltrans model suite and the first emulator for a state-of-the-art x-ray reflection model incorporating relativistic effects with 17 physically meaningful model parameters. We use Principal Component Analysis to create a light-weight neural network that is able to preserve correlations between complex atomic lines and simple continuum, enabling consistent modelling of key parameters of scientific interest. We achieve a $\mathcal {O}(10^2)$ times speed up over the original model in the most conservative conditions with $\mathcal {O}(1\%)$ precision over all 17 free parameters in the original numerical model, taking full posterior fits from months to hours. We employ Markov Chain Monte Carlo sampling to show how we can better explore the posteriors of model parameters in simulated data and discuss the complexities in interpreting the model when fitting real data.