bluuebunny/crossref_metadata_2025_split huggingface dataset:
Platelet Activation Pathways Controlling Reversible Integrin αIIbβ3 Activation
Authors: Zou Jinmi , Sun Siyu , De Simone Ilaria , ten Cate Hugo , de Groot Philip G. , de Laat Bas , Roest Mark , Heemskerk Johan W.M. , Swieringa Frauke 
Published: June 2024

Abstract
Background Agonist-induced platelet activation, with the integrin αIIbβ3 conformational change, is required for fibrinogen binding. This is considered reversible under specific conditions, allowing a second phase of platelet aggregation. The signaling pathways that differentiate between a permanent or transient activation state of platelets are poorly elucidated.
Objective To explore platelet signaling mechanisms induced by the collagen receptor glycoprotein VI (GPVI) or by protease-activated receptors (PAR) for thrombin that regulate time-dependent αIIbβ3 activation.
Methods Platelets were activated with collagen-related peptide (CRP, stimulating GPVI), thrombin receptor-activating peptides, or thrombin (stimulating PAR1 and/or 4). Integrin αIIbβ3 activation and P-selectin expression was assessed by two-color flow cytometry. Signaling pathway inhibitors were applied before or after agonist addition. Reversibility of platelet spreading was studied by microscopy.
Results Platelet pretreatment with pharmacological inhibitors decreased GPVI- and PAR-induced integrin αIIbβ3 activation and P-selectin expression in the target order of protein kinase C (PKC) > glycogen synthase kinase 3 > β-arrestin > phosphatidylinositol-3-kinase. Posttreatment revealed secondary αIIbβ3 inactivation (not P-selectin expression), in the same order, but this reversibility was confined to CRP and PAR1 agonist. Combined inhibition of conventional and novel PKC isoforms was most effective for integrin closure. Pre- and posttreatment with ticagrelor, blocking the P2Y12 adenosine diphosphate (ADP) receptor, enhanced αIIbβ3 inactivation. Spreading assays showed that PKC or P2Y12 inhibition provoked a partial conversion from filopodia to a more discoid platelet shape.
Conclusion PKC and autocrine ADP signaling contribute to persistent integrin αIIbβ3 activation in the order of PAR1/GPVI > PAR4 stimulation and hence to stabilized platelet aggregation. These findings are relevant for optimization of effective antiplatelet treatment.
Anarchism: war, violence and scapegoating
Authors: Stevens Simon , Kinna Ruth 
Published: June 2024

Abstract
This article gives an anarchist account of politics as war to theorise an anarchist Realpolitik. Mikhail Vereshchagin’s killing in War and Peace provides the springboard to review the claim that sovereign power secures peace and to explore the merit of scapegoating. We elaborate the anarchist account of politics as war by juxtaposing Foucault’s and Proudhon’s interpretations of Hobbes’ sovereign and adopt the term ‘reverse ethics’ to describe the proposal that citizens retain the philosophical right to forcefully disrupt the state’s supposed peace. The anarchist embrace of war conflicts with the common view that anarchism’s alignment of the means and ends of political action commits anarchists to reject violence. To meet this objection, we discuss Frazer and Hutchings’ theorisation of anarchist ambivalence. We argue that reverse ethics complicates tensions between the presumption of non-violence and the critique of state violence. To consider the use of force in liberal democracy, we connect reverse ethics to Hyams’ anarchist defence of upward scapegoating and targeted assassination. Considering applications in contemporary politics, we argue that reverse ethics constructively redirects attention from the need to justify political violence to the demand to hold sovereign power to its contractual obligation. This is anarchist Realpolitik.
Deference in Human Rights Adjudication
Authors: Chan Cora 
Published: June 2024

Abstract
In human rights adjudication, courts sometimes face issues that they lack the expertise or constitutional legitimacy to resolve. One way of dealing with such issues is to ‘defer’, or accord a margin of appreciation, to the judgments of public authorities. Although there is a rich literature on the subject of deference, two important questions remain unresolved: what devices courts should use to exercise deference, and how deference can be made more workable for judges and predictable for litigants. This book offers the first comprehensive analysis of these questions. It introduces six devices for deference (namely, the burden of proof, standard of proof, standard of review, giving of weight, choice of interpretation, and choice of remedy), analyses how courts should choose amongst them, and proposes techniques for rendering deference practicable. The book’s arguments will enable human rights adjudication to be more principled and more in line with the rule of law and separation of powers. The book has two distinctive features. First, it engages with the jurisprudence of six common law jurisdictions that apply a structured proportionality test in rights adjudication, namely, Canada, Hong Kong, Ireland, Israel, New Zealand, and the United Kingdom. Second, the book offers guidelines for judges who wish to apply its theoretical arguments. Combining theory with practice in a broad range of jurisdictions, the book will be an important reference for researchers and students of constitutional theory, comparative constitutional law, and human rights law around the world. It will also assist practitioners, judges, and policymakers who have to grapple with issues of deference in adjudication.
Introduction
Authors: Chan Cora 
Published: June 2024

Abstract
This chapter sets out the two core questions that this book seeks to explore: what devices courts should use to exercise deference, and how deference can be made more workable for judges and predictable for litigants. The chapter then defines judicial deference as a court granting leeway to the legislature or executive—leeway that it would not have granted if it had merely considered the balance of reasons bearing on the rights issue at hand—for reasons arising from the comparative institutional positions of the court and the political branches of government. The chapter further explains the scope, methodology, and significance of the book, situates the book within the relevant literature, and addresses possible objections to the book’s ambitions.
Reasons for Deference
Authors: Chan Cora 
Published: June 2024

Abstract
This chapter draws a distinction between grounds for deference (which are tied to the fulfilment of objective values) and factors for considering whether such grounds exist. It argues that in polities that satisfy certain background conditions (as do the jurisdictions on whose case law the book draws), the courts have three sets of grounds for exercising deference: grounds that relate to arriving at the correct outcome in the case at hand, to respect for constitutional legitimacy, and to other considerations that the court should take into account in adjudication. The chapter maps out the relationship between such grounds and the main factors for considering whether they exist.
Devices for Deference
Authors: Chan Cora 
Published: June 2024

Abstract
This chapter explains that the courts have at their disposal the following six devices for exercising deference: the burden of proof, standard of proof, standard of review, giving of weight to views, choice of interpretation (ie adopting an interpretation of a constitutional provision that affords the government a broader permissible scope of action), and choice of remedy. The chapter illustrates how the devices can be used at the various stages of rights adjudication—ie rights definition, limitation, and remedial stages—and does so by drawing on case law from Canada, Hong Kong, Ireland, Israel, New Zealand, and the United Kingdom.
Choice of Device I: Type of Reasons
Authors: Chan Cora 
Published: June 2024

Abstract
The chapter explores how courts should choose a device to fulfil a certain reason for deference. It dissects the nature of each device and highlights situations where the use of a particular device is needed to express a particular reason for deference. For example, the standard of review cannot be used to express the imperative to minimize the social costs of an erroneous ruling, which should instead be expressed using the burden and standard of proof. Where the facts that give rise to reasons for deference discriminate between deference on various issues, the court should determine which issue to defer on according to which set of facts exists. For example, if the public authority has superior expertise on the third, but not the second, limb of the proportionality test, the court should defer on the former not the latter to give effect to the expertise reason for deference.
Choice of Device III: Practicability
Authors: Chan Cora 
Published: June 2024

Abstract
Chapter 6 explores how the methods of determining when, how, and how much to defer can be made more workable and predictable without undue compromise of those methods’ ability to reflect the normative reasons for deference in a particular case. Noting that there is an inevitable trade-off between making methods of deference more practicable and making them more flexible to account for variations in the degree and means of deference across contexts, the chapter expounds the factors that determine where the balance between these two considerations should lie and introduces four sets of techniques for striking that balance: (1) using rules, presumptions, and factorial analysis; (2) mapping certain normative considerations onto specific deference devices; (3) developing clear and reliable indicators of deference; and (4) developing finite scales for various devices and levels of scrutiny that combine various devices.
Thinking like a pathologist: Morphologic approach to hepatobiliary tumors by ChatGPT
Authors: Laohawetwanit Thiyaphat , Apornvirat Sompon , Namboonlue Chutimon 
Published: June 2024

Abstract

Objectives
This research aimed to evaluate the effectiveness of ChatGPT in accurately diagnosing hepatobiliary tumors using histopathologic images.

Methods
The study compared the diagnostic accuracies of the GPT-4 model, providing the same set of images and 2 different input prompts. The first prompt, the morphologic approach, was designed to mimic pathologists’ approach to analyzing tissue morphology. In contrast, the second prompt functioned without incorporating this morphologic analysis feature. Diagnostic accuracy and consistency were analyzed.

Results
A total of 120 photomicrographs, composed of 60 images of each hepatobiliary tumor and nonneoplastic liver tissue, were used. The findings revealed that the morphologic approach significantly enhanced the diagnostic accuracy and consistency of the artificial intelligence (AI). This version was particularly more accurate in identifying hepatocellular carcinoma (mean accuracy: 62.0% vs 27.3%), bile duct adenoma (10.7% vs 3.3%), and cholangiocarcinoma (68.7% vs 16.0%), as well as in distinguishing nonneoplastic liver tissues (77.3% vs 37.5%) (Ps ≤ .01). It also demonstrated higher diagnostic consistency than the other model without a morphologic analysis (κ: 0.46 vs 0.27).

Conclusions
This research emphasizes the importance of incorporating pathologists’ diagnostic approaches into AI to enhance accuracy and consistency in medical diagnostics. It mainly showcases the AI’s histopathologic promise when replicating expert diagnostic processes.
The seed morphospace, a new contribution towards the multidimensional study of angiosperm sexual reproductive biology
Authors: Carta Angelino , Vandelook Filip , Ramírez-Barahona Santiago , Chen Si-Chong , Dickie John , Steinbrecher Tina , Thanos Costas A , Moles Angela T , Leubner-Metzger Gerhard , Mattana Efisio 
Published: June 2024

Abstract

Background
The evolutionary success of flowering plants is associated with the vast diversity of their reproductive structures. Despite recent progress in understanding angiosperm-wide trends in floral structure and evolution, a synthetic view of the diversity in seed form and function across angiosperms is lacking.

Scope
Here we present a roadmap to synthesize the diversity of seed forms in extant angiosperms, relying on the morphospace concept, i.e. a mathematical representation which relates multiple traits and describes the realized morphologies. We provide recommendations on how to broaden the range of measurable traits beyond mass, by using key morphological traits representative of the embryo, endosperm and seed coat but also fruit attributes (e.g. dehiscence, fleshiness). These key traits were used to construct and analyse a morphospace to detect evolutionary trends and gain insight into how morphological traits relate to seed functions. Finally, we outline challenges and future research directions, combining the morphospace with macroevolutionary comparative methods to underline the drivers that gave rise to the diversity of observed seed forms.

Conclusions
We conclude that this multidimensional approach has the potential, although still untapped, to improve our understanding of covariation among reproductive traits, and further elucidate angiosperm reproductive biology as a whole.
The Invisible Sainthood of Mariana de Jesús Paredes y Flores
Authors: Friedman Hannah Joy 
Published: June 2024

Abstract
What did it mean for portrait images to generate recognition of early modern individuals as saints? Did images make sainthood visible through a person’s particularities or their conformity to perfect models? To be recognisable as an historical individual was not necessarily compatible with being recognised as a saint, either officially by Rome, or experientially by devotees. Early images of Quito’s most prominent candidate for sainthood, Mariana de Jesús Paredes y Flores (1618–1645), throw into sharp relief the pressure that posthumous candidacy for sainthood brought to bear on portrait images, especially of women. Mariana’s imagery reconfigures the relationship among visibility, individuality and recognition that posed a common problem for aspiring saints’ portraits. Far from being transparent post-Tridentine propaganda, Mariana’s early iconography works against the grain of the portrait genre, creatively addressing the tensions between individual likeness and conformity to perfect models, and between concealing sainthood and making it visible.
Enhancing power generation via an adaptive neuro-fuzzy and backstepping maximum-power-point tracking approach for photovoltaic single-ended primary inductor converter system
Authors: Chnini Khalil , Jouini Houda , Allagui Hatem , Mami Abdelkader 
Published: June 2024

Abstract
The distinct characteristics of photovoltaic generators related to power and current present a complex problem in terms of optimizing their power output. To tackle this, maximum-power-point tracking techniques such as the adaptive neuro-fuzzy inference system are frequently utilized for their swift adaptability and reduced fluctuations. In addition, the backstepping controller is often selected to handle both linear and non-linear systems due to its exceptional reliability. The purpose of this research is to propose an innovative method that merges the adaptive neuro-fuzzy inference system and backstepping controller to refine the tracking of the optimal power point and to bolster the stability of the photovoltaic system in the face of unpredictable scenarios, such as those presented by the Ropp irradiance examination, which utilizes a single-ended primary inductor converter as a stage for power electronics adaptation. Simulations conducted using MATLAB®/Simulink® demonstrate that the combination of adaptive neuro-fuzzy inference system and backstepping controller achieves an impressive efficiency of 99.6% and exhibits fast, robust, and accurate responses compared with other algorithms such as artificial neural networks combined with the backstepping controller and conventional perturb and observe algorithm.
Association between magnesium, erythropoietin resistance and mortality: the Japanese Dialysis Outcomes and Practice Patterns Study (J-DOPPS)
Authors: Kato Sawako , Wang Jui , Onishi Yoshihiro , Nangaku Masaomi 
Published: June 2024

ABSTRACT

Background
Limited data are now available to evaluate the relationship between serum magnesium level, anemia and mortality in the dialysis population.

Methods
Using data from the Japanese Dialysis Outcomes and Practice Patterns Study (J-DOPPS) phases 5 and 6, we analyzed the association between serum magnesium (s-Mg) levels and the erythropoiesis-stimulating agents resistance index (ERI) as the primary outcome. To estimate the longitudinal relationship, a mixed-effect model was used with ERI at each 4-month period as the dependent variable and quintiles of s-Mg at the previous 4-month period as the independent variable. We also examined incidence of infectious events, and the all-cause and cardiovascular disease (CVD)-related deaths as secondary outcomes by Cox regression with quintiles of s-Mg at baseline.

Results
Of the 4776 participants in J-DOPPS, 1650 were included in the analysis. The median of s-Mg at baseline was 2.5 mg/dL. A significant linear association of s-Mg with ERI (P for trend &lt;.001) was revealed. Low and high s-Mg levels were not associated with the clinical outcomes of interest, except for the highest quintile of s-Mg being significantly associated with lower incidence of all-cause mortality and CVD-related deaths compared with the middle (reference) quintile.

Conclusions
We observed that lower s-Mg levels subsequently induced higher ERI and that mild higher s-Mg levels were possibly associated with good rather than poor outcomes in Japanese hemodialysis patients. Adjustment of s-Mg levels may be proposed as a new strategy at a low cost and risk to reduce the risk of premature mortality.
Machine Learning-Based Prediction of Hemoglobinopathies Using Complete Blood Count Data
Authors: Schipper Anoeska , Rutten Matthieu , van Gammeren Adriaan , Harteveld Cornelis L , Urrechaga Eloísa , Weerkamp Floor , den Besten Gijs , Krabbe Johannes , Slomp Jennichjen , Schoonen Lise , Broeren Maarten , van Wijnen Merel , Huijskens Mirelle J A J , Koopmann Tamara , van Ginneken Bram , Kusters Ron , Kurstjens Steef 
Published: June 2024

Abstract

Background
Hemoglobinopathies, the most common inherited blood disorder, are frequently underdiagnosed. Early identification of carriers is important for genetic counseling of couples at risk. The aim of this study was to develop and validate a novel machine learning model on a multicenter data set, covering a wide spectrum of hemoglobinopathies based on routine complete blood count (CBC) testing.

Methods
Hemoglobinopathy test results from 10 322 adults were extracted retrospectively from 8 Dutch laboratories. eXtreme Gradient Boosting (XGB) and logistic regression models were developed to differentiate negative from positive hemoglobinopathy cases, using 7 routine CBC parameters. External validation was conducted on a data set from an independent Dutch laboratory, with an additional external validation on a Spanish data set (n = 2629) specifically for differentiating thalassemia from iron deficiency anemia (IDA).

Results
The XGB and logistic regression models achieved an area under the receiver operating characteristic (AUROC) of 0.88 and 0.84, respectively, in distinguishing negative from positive hemoglobinopathy cases in the independent external validation set. Subclass analysis showed that the XGB model reached an AUROC of 0.97 for β-thalassemia, 0.98 for α0-thalassemia, 0.95 for homozygous α+-thalassemia, 0.78 for heterozygous α+-thalassemia, and 0.94 for the structural hemoglobin variants Hemoglobin C, Hemoglobin D, Hemoglobin E. Both models attained AUROCs of 0.95 in differentiating IDA from thalassemia.

Conclusions
Both the XGB and logistic regression model demonstrate high accuracy in predicting a broad range of hemoglobinopathies and are effective in differentiating hemoglobinopathies from IDA. Integration of these models into the laboratory information system facilitates automated hemoglobinopathy detection using routine CBC parameters.
Potential exposure of honey bees to neonicotinoid seed treatments in US rice
Authors: Bateman Nicholas Ryan , Thrash Benjamin C , Crow Whitney D , Towles Tyler B , Cook Don R , Lorenz Gus M , Gore Jeffrey 
Published: June 2024

Abstract
Neonicotinoid insecticide seed treatments are commonly used in rice (Oryza sativa) production to control rice water weevil (Lisorhoptrus oryzophilus). With the use of neonicotinoid seed treatments, there is potential that honey bees (Apis mellifera) could be exposed to neonicotinoids through translocation to the pollen. Studies were conducted in 2015 and 2016 to determine the level of neonicotinoids present in flag leaves, pollen, and grain of rice. Thiamethoxam was applied as a seed treatment and foliar prior to flooding. Clothianidin was applied as a seed treatment and as a foliar at a preflood and postflood timing. Subsamples of flag leaves, pollen, and grain were analyzed for positive neonicotinoid detections and abundance. Thiamethoxam was detected in 8.9% of samples and clothianidin was detected in 1.4% of samples. For both thiamethoxam and clothianidin, more positive samples were observed in flag leaf samples than in pollen or grain. An average of 4.30 ng/g of thiamethoxam was detected in flag leaves from seed-applied thiamethoxam. An average of 1.25 ng/g of clothianidin was found in flag leaves from a preflood application of clothianidin. A survey of honey bees present in rice fields was conducted in Mississippi and Arkansas to determine the abundance of honey bees present in rice fields based on the time of day. Honey bee densities were low in rice, with less than 5% and 3% positive detections observed in Mississippi and Arkansas, respectively. More positive detections and higher densities of honey bees were observed for mid-day sampling than for morning or evening sampling.
Spatial disparities in access to NHS dentistry: a neighbourhood-level analysis in England
Authors: Clark Stephen D 
Published: June 2024

Abstract
Over the past decade, access to National Health Service (NHS) dentistry in England has been problematic. There are increasing media reports of patients being unable to find treatment at a local NHS dentist. However, the extent of this issue varies by location and by the characteristics of the neighbourhood. The study uses official data sources on NHS dental provision and population. Travel accessibility is measured using car journey times. An advanced form of Floating Catchment Area accessibility is used, which accounts for supply competition, varying catchments, and distance decay. Spatial availability and accessibility indices are calculated. Ways in which the method can be used to explore various types of ‘what-if’ scenarios are outlined. Both availability and accessibility vary by the level of neighbourhood deprivation and the urban/rural nature of the neighbourhood. A case study, based on a real-world situation, shows the impact on the local neighbourhood of the closure of a dental practice. For all neighbourhoods, NHS dental provision is generally less than would be needed to provide basic dental care. The interpretation of outputs needs to take account of edge-effects near to Scotland and Wales. Possible improvements include the inclusion of other modes of travel and the exclusion of the population that does not want to access NHS care.