bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimal dosing regimen of CD73 blockade improves tumor response to radiotherapy through iCOS downregulation
Authors: Meziani Lydia , Gerbé de Thoré Marine , Clémenson Céline , Liu Winchygn , Laurent Pierre-Antoine , Mondini Michele , Vozenin Marie-Catherine , Deutsch Eric 
Published: June 2023

BackgroundIrradiation (IR) and immune checkpoint inhibitor (ICI) combination is a promising treatment modality. However, local and distance treatment failure and resistance can occur. To counteract this resistance, several studies propose CD73, an ectoenzyme, as a potential target to improve the antitumor efficiency of IR and ICI. Although CD73 targeting in combination with IR and ICI has shown attractive antitumor effects in preclinical models, the rationale for CD73 targeting based on CD73 tumor expression level deserves further investigations.MethodsHere we evaluated for the first time the efficacy of two administration regimens of CD73 neutralizing antibody (one dose vs four doses) in combination with IR according to the expression level of CD73 in two subcutaneous tumor models expressing different levels of CD73.ResultsWe showed that CD73 is weakly expressed by MC38 tumors even after IR, when compared with the TS/A model that highly expressed CD73. Treatment with four doses of anti-CD73 improved the TS/A tumor response to IR, while it was ineffective against the CD73 low-expressing MC38 tumors. Surprisingly, a single dose of anti-CD73 exerted a significant antitumor activity against MC38 tumors. On CD73 overexpression in MC38 cells, four doses of anti-CD73 were required to improve the efficacy of IR. Mechanistically, a correlation between a downregulation of iCOS expression in CD4+T cells and an improved response to IR after anti-CD73 treatment was observed and iCOS targeting could restore an impaired benefit from anti-CD73 treatment.ConclusionsThese data emphasize the importance of the dosing regimen for anti-CD73 treatment to improve tumor response to IR and identify iCOS as part of the underlying molecular mechanisms. Our data suggest that the selection of appropriate dosing regimen is required to optimize the therapeutic efficacy of immunotherapy–radiotherapy combinations.
Increased risk of congenital malformations in offspring born to women with systemic lupus erythematosus in South Korea: a nationwide population-based study
Authors: Jung Young Mi , Park Jin Kyun , Oh Min-Jeong , Park Chan-Wook , Park Joong Shin , Jun Jong Kwan , Lee Seung Mi , Cho Geum Joon 
Published: June 2023

ObjectivesThe aim of this study was to determine the risk of congenital malformations in offspring born to women with systemic lupus erythematosus (SLE).MethodsThis nationwide population-based study included Korean women who had a singleton pregnancy. The risk of congenital malformations in women with SLE was compared with those without SLE. Multivariable analyses were performed to estimate the OR of congenital malformations. In a sensitivity analysis, the risk of malformation was compared between the offspring of women with SLE and those of propensity-matched women without SLE.ResultsOf a total of 3 279 204 pregnant women, 0.1% had SLE and their offspring had a higher frequency of congenital malformations (17.13% vs 11.99%, p<0.0001). After adjustment for age, parity, hypertension, diabetes, and fetal sex, the SLE group was found to be associated with an increased risk of congenital malformations in the nervous system (adjusted OR (aOR, 1.90; 95% CI, 1.20 to 3.03), eye, ear, face, and neck (aOR, 1.37; 95% CI, 1.09 to 1.71), circulatory system (aOR, 1.91; 95% CI, 1.67 to 2.20), and musculoskeletal system (aOR, 1.26; 95% CI, 1.05 to 1.52). Even after propensity matching, some of the tendencies were maintained.ConclusionsThis nationwide population-based study in South Korea indicates that compared with the general population, neonates born to SLE mothers have a slightly increased risk of congenital malformations affecting the nervous system, head and neck, cardiovascular system, and musculoskeletal system. When a woman with lupus becomes pregnant, careful fetal ultrasound and newborn screening can be helpful in identifying the risk of potential malformations.
The MDM2–p53 Antagonist Brigimadlin (BI 907828) in Patients with Advanced or Metastatic Solid Tumors: Results of a Phase Ia, First-in-Human, Dose-Escalation Study
Authors: LoRusso Patricia , Yamamoto Noboru , Patel Manish R. , Laurie Scott A. , Bauer Todd M. , Geng Junxian , Davenport Teffany , Teufel Michael , Li Jian , Lahmar Mehdi , Gounder Mrinal M. 
Published: June 2023

Abstract

Brigimadlin (BI 907828) is an oral MDM2–p53 antagonist that has shown encouraging antitumor activity in vivo. We present phase Ia results from an open-label, first-in-human, phase Ia/Ib study investigating brigimadlin in patients with advanced solid tumors (NCT03449381). Fifty-four patients received escalating doses of brigimadlin on day 1 of 21-day cycles (D1q3w) or days 1 and 8 of 28-day cycles (D1D8q4w). Based on dose-limiting toxicities during cycle 1, the maximum tolerated dose was selected as 60 mg for D1q3w and 45 mg for D1D8q4w. The most common treatment-related adverse events (TRAE) were nausea (74.1%) and vomiting (51.9%); the most common grade ≥3 TRAEs were thrombocytopenia (25.9%) and neutropenia (24.1%). As evidence of target engagement, time- and dose-dependent increases in growth differentiation factor 15 levels were seen. Preliminary efficacy was encouraging (11.1% overall response and 74.1% disease control rates), particularly in patients with well-differentiated or dedifferentiated liposarcoma (100% and 75% disease control rates, respectively).

Significance:
We report phase Ia data indicating that the oral MDM2–p53 antagonist brigimadlin has a manageable safety profile and shows encouraging signs of efficacy in patients with solid tumors, particularly those with MDM2-amplified advanced/metastatic well-differentiated or dedifferentiated liposarcoma. Further clinical investigation of brigimadlin is ongoing.
See related commentary by Italiano, p. 1765.
This article is highlighted in the In This Issue feature, p. 1749
Versions of Local Time
Authors: Michon John A. 
Published: June 2023

Abstract
In the interdisciplinary study of time we see a shift from a physicalistic paradigm, as we know it from Julius T. Fraser’s work, to a rather more cognitive-theoretical approach, as advanced, for instance, by Allen Newell, who takes mental activity to consist of a complex, active search through a problem space. In this article, I compare some recent efforts of physically oriented researchers Prigogine and Barbour with the cognitive approach taken by chronopsychologists Lakoff, Gibson, Jones, Leyton and others. It stipulates that the classical notion of temporality as an absolute property of the universe has in fact been replaced by versions of local time. Recent examples of timing on the basis of local time include temporal information processing according to the demands of metaphor, scripts, dynamic attention, and more. The common ground appears to be that time is a derived entity, based on embodied (inborn) as well as situated (acquired) processing activity.
The Temporal Challenge of Hope
Authors: Ostovich Steve 
Published: June 2023

Abstract
Hope informs and inspires our actions. We look to succeed at achieving what we hope for, and this orients our hope towards the future in which time is conceived linearly. The connection between hope as success and linear time creates several difficulties when we seek to defend our hope. This is especially the case regarding past hopes and the dead, who can no longer hope for themselves. J. T. Fraser’s hierarchical theory of time’s conflicts is a complex theory of time that makes possible thinking through hope more critically.
Towards an Interdisciplinary Approach to Time in Fiction
Authors: Ksenofontova Alexandra 
Published: June 2023

Abstract
The paper surveys five major perspectives on studying time in fiction: narratology, history of temporal regimes, temporal pluralism, aesthetics of time, and politics of time. It argues that these approaches have so far remained largely unintegrated, leading to a separation between areas of literary criticism that are in reality closely linked. In particular, some approaches separate time as subject from time as the principal element of narratives. Some approaches disregard the transhistorical plurality of temporal experiences, while others turn a blind eye to larger historical changes in the perception of time. Finally, some scholars choose to focus only on temporal aesthetics, while others explore only the fictional politics of time. Scrutinizing these three schisms of studying time in literary criticism, the paper argues for a re-integrated approach that accommodates insights from various disciplines and adopts a broader perspective on time and temporality in fiction.
Time, Conflicts and Chance
Authors: Lestienne Rémy 
Published: June 2023

Abstract
After having briefly introduced the circumstances by which J. T. Fraser was led to build his theory of Time as Conflicts and the way this notion takes consistency through several levels, according to the abilities of the inert or living beings that populate the world, I try to analyze and comment upon them. At each of these levels, the complexity of time is manifested by concepts that oppose each other: permanence and change, movement and rest, divisibility and atomicity, chance and irreversibility, increasing entropy and local decreases, etc. In Fraser’s view, as in mine, the most important issues concern the division of time into past, present, and future, and the irreversibility of the world’s course. Fraser writes that these concepts become consistent only with the appearance of life, because only living beings (and even more so the human race) perceive these things in their Umwelt. Without disagreeing with him on this point, I emphasize the dominant role that Chance plays in the evolution of the world, at all levels considered by Fraser (except atemporality), even if living systems learned, sooner and better than any others, how to take advantage of their position as thermodynamically open systems. I use this argument to suggest, after Alfred North Whitehead, that next to the time of the living we must posit the existence of an objective motor of the world, restoring the ontology of the division of events into past, present, and future, as well as the specificity of the present.
A Different Cup of Time
Authors: Turner Frederick 
Published: June 2023

Abstract
This essay provides a poetic picture of the author’s experience of the International Society for the Study of Time, of which he has been a member since the 1970s. It includes excerpts from the author’s poetry, including from “Turn Again,” an unpublished work of “semantic autobiography” that charts the process by which the meanings of words emerge and deepen over a lifetime. The word “Time,” especially as characterized by the founder of the Society, J. T. Fraser, is the central actor in the Society’s social and intellectual drama.
Obstetric Violence: Sterilisation without Consent. The Case of Y.P. v. Russian Federation
Authors: den Exter André 
Published: June 2023

Abstract
On 20 September 2022, the European Court of Human Rights (ECtHR) delivered its judgment in a remarkable case on sterilisation without the patient’s consent, Y.P. v Russian Federation (ECtHR, application no. 43399/13, 20 September 2022). According to the Court, there is no inhuman and degrading treatment, but it was a justified medical procedure. However, the Court did conclude a violation of the right to private life, under Article 8 ECHR. This outcome is at odds with an earlier sterilisation case without consent, V.C. v Slovakia (V.C. v. Slovakia, ECtHR application no. 18968/07, 8 November 2011). The question is how both rulings can be understood, especially the legal consideration regarding the prohibition of torture. After all, both cases lacked the patient’s consent.
Bringing Together the Criminologies of Atrocity and Serious Economic Crimes
Authors: Aydın-Aitchison Andy 
Published: June 2023

Abstract
The paper reflects on the value of linking criminological research on atrocity with that on serious economic crime. The two areas of criminological research are outlined briefly, before common challenges around complexity and interdependence are set out. An example of a criminal career encompassing both atrocity and serious economic criminality is put forward to support claims that atrocity and economic crime can usefully be studied together. Three further examples of research are discussed to show the possible merits of bringing together two criminological strands. Ultimately, studying the two forms of criminality together would respect the lived experience of victims, who see firsthand how atrocity and serious economic crime go hand in hand.
How many co-authors had Perpetua and Saturus?
Authors: Braginskaya Nina V. , Lebedev Pavel N. 
Published: June 2023

Abstract
The early Christian work “The Passion of Saints Perpetua and Felicity” consists of different parts combined into a single book. Three parts are generally accepted: 1) Perpetua’s Notes, 2) Saturus’s Vision, 3) the Eyewitness story and the Prologue and Epilogue written by the same author. We argue that the Prologue plus Epilogue and the Eyewitness story had different authors and there was one more person, who was neither a participant nor a contemporary of the Carthaginian martyrdom. The results of his activity can be found in short sentences connecting the parts, as well as in violations of the structure of the narrative and a serious mistake made in the enumeration of the arrested catechumens. The authors claim also that this kind of collection as in The Passion had no analogues in ancient classical literature and followed the model of the New Testament.
Muslims’ Experience with Islamophobia in Slovakia
Authors: Kosárová Dominika 
Published: June 2023

Abstract
In several European countries, Slovakia included, Islamophobia has been shaped by the challenges faced by Europe (an influx of refugees, terrorism, rise of the far right) since circa 2015. Anti-Muslim narratives have penetrated politics as well as the media and are shared by a significant part of the Slovak population. This article aims at contributing to the existing research on Islamophobia in Slovakia through an exploratory case study focusing on a different perspective, Muslims themselves. The main objective of the research is to identify the magnitude and character of Islamophobia experienced by Muslims in Slovakia since 2015. Data were gathered using an online survey. The findings revealed not only the extent but also the most common features of Islamophobia experienced by Muslims, including the type of incidents, the places of their occurrence, and the nexus between Islamophobic incidents and origin of respondents (Slovak or foreign), external manifestation of their faith, and sex.
Franz Brentano’s Conception of the Object and its Intentional Inexistence
Authors: Antonelli Mauro 
Published: June 2023

Abstract
In line with earlier works, this article argues for a “continuist” interpretation of Brentano’s conception of intentionality. It maintains that Brentano’s conception of intentionality rests on a complex set of notions, which are reduced to a minimal core or applied more fully depending on the complexity of the mental phenomenon under consideration and perspective from which it is analyzed. The article positions this conceptual structure in relation to theories of objects developed within the framework of late- and Neo-Scholastic philosophy where, since the psychic act can relate to its object in different ways, the different types and roles of objects must be distinguished. This theory of objects enables Brentano to reinterpret Aristoteles’s idea of the intentionality of mental phenomena in light of the commentaries and interpretations of Thomas Aquinas while also giving space to other medieval texts.
Brentanians against Relationalism about Colours
Authors: Taieb Hamid 
Published: June 2023

Abstract
The aim of my article is to present the critique by Brentanians – more precisely, by Brentano himself and his students Stumpf and Marty – of the thesis that colours are properties that are relational to a perceiver. For Brentanians, colours are monadic physical properties. Brentanians, I will show, think that colours do not exhibit a relationality to perception when we experience them, and that the concepts of them do not contain any mark representing a relation to perception; this phenomenological and logical non-relationality, they think, allows them to hold that colours are not relational by nature. Despite arguing that colours are monadic and physical, Brentanians also hold that colours do not exist in reality, and in their opinion these two theses are perfectly compatible. I will further show that although Brentanians (especially Marty) claim that colours are monadic, they nonetheless allow for a loose relationality of colours to perception which is, however, identical to that of any other physical property. I will conclude by discussing some interesting consequences of the Brentanian theory for contemporary debates about colours.
Uganda’s Post-War Transitional Justice Process
Authors: Kirabira Tonny Raymond , Choukroune Leïla 
Published: June 2023

Abstract
This article examines the existing post-war recovery framework employed in Uganda to address concerns with housing, land and property (hlp) rights, particularly in Uganda’s post-war recovery period. It explores the integration of special categories of victims, i.e., internally displaced persons (idp s) and children born of war (cbw), with a key focus on how hlp rights are integrated into – or left out of – the transitional justice (tj) process. hlp rights fit within the broader pictures of customary practices and tj, since they enable idp s and cbw to integrate into the post-war communities. Our findings from the Uganda case study cast some doubt on the current process and aim to influence future interventions by emphasising that progress with securing hlp rights for those affected by war and violence is an integral part of any legitimate post-war recovery process and tj interventions.
The Practical Reality and Efficacy of International Humanitarian Law: Some Reflections
Authors: Greenwood Christopher 
Published: June 2023

Abstract
This article considers certain aspects of the reality and efficacy of ihl. It looks at problems concerning the scope of ihl, including the question of what constitutes an armed conflict, the difficulties of disentangling international and non-international elements in some armed conflicts and debates about the application of ihl in United Nations peacekeeping. The article also examines whether ihl has acquired detail at the expense of practicality and calls for training of military personnel aimed at the development of a humanitarian reflex. It discusses the relationship between ihl and human rights law. Finally, it considers some of the problems in securing compliance with ihl.
Rules of Engagement and the Situation of Individual Self-Defence: Applicable Law and Coherence with Operational Context
Authors: McLaughlin Rob 
Published: June 2023

Abstract
Within a broader discussion as to the place and role of self-defence within Rules of Engagement, this article seeks to describe some of the drafting and application issues that often present when employing Rules of Engagement – as a distillation of law, policy, operational context, and capability – to resolve, or to encapsulate the resolution achieved, in each mission-specific dialogue between operational context and the law of individual self-defence. To this end, the analysis will focus primarily (but not exclusively) upon the availability to military members of the ‘right’ of individual self-defence in otherwise law of armed conflict-governed operations.
Johanna Eleonora Petersens Gespräche des Hertzens mit GOTT (1689) zwischen Gebet, Selbstgespräch und Dialog
Authors: Müller Sarah 
Published: June 2023

Abstract
J. E. Petersen’s Gespräche des Hertzens mit GOTT (Conversations of the Heart with GOD) is a soliloquy in the form of prayer that stages dialogue. Its complexity can be illustrated by two communication complexes. A first communication complex comprises the triadic dialogue between the Ego and an inner corresponding You – immanent in a single individual –, mediated by God. It can offer a moment of contemplation to the readers. In a scheme based on the religious history of Pietism the Ego in the confession of the Bible word turns equally to its inner You and to God. Mediated by the Holy Spirit, a personal experience of the scriptural word is evoked, leading to self-conviction. During this praxis pietatis, the reader takes over the position of the praying person – that is the Ego and the You. Petersen’s ‘Heart-Conversations’ are paradigmatic for a connection of literary studies and religious studies: on the one hand, for a communication scheme-based justification of the dialogical in the soliloquy and, on the other hand, as a communication complex of the staged, performative dialogue in pietistic written prayer.
Haec revolutionis ars
Authors: Ramos Grané Marta 
Published: June 2023

Abstract
This article aims to shed some light on the functioning of the quadrangle, a combinatorial mnemonic mechanism devised by Iacobus Publicius and of great tradition in the artes memorativae. The absence of an explanation of how it works in Publicius’ text has meant that many scholars have not approached this quadrangle. We believe that such an explanation can now be provided by an early 16th century treatise writer, Iohannes Romberch, who not only included this mental instrument in his Congestorium, but also tried to explain it and make it functional. This same author also proposed a second mechanism, very similar to the previous one, to give form to a specific type of images, the inscriptiones.
Paleocene fossil wood from Patagonia with storied rays and comments on the fossil record of this character
Authors: Ruiz Daniela P. , Pujana Roberto R. , Brea Mariana 
Published: June 2023

Summary
The storied structure in wood anatomy is considered derived and highly specialized, and is present in some related families. The first records of this character are from the Cretaceous, but it is scarce in the Cretaceous and Paleocene, and apparently absent until the Eocene in the temperate Southern Hemisphere. Using standard methodology, we describe the anatomy of a fossil wood from the early Paleocene of Patagonia (Salamanca Formation). The fossil wood, assigned to a new genus and species Elizabethiaxylon patagonicum related to the Malvaceae, is characterized by its diffuse-porous wood, solitary vessels, simple perforation plates, apotracheal banded axial parenchyma, and mostly biseriate storied rays. The storied structure in this wood is one of the oldest records from Gondwana.
Notes on a Renaissance Bestiary by Ulisse Aldrovandi
Authors: Acciarino Damiano 
Published: June 2023

Abstract
A unique codex in the University of Bologna, crafted as a single monographic volume, transmits an extremely interesting treatise by the naturalist and antiquary Ulisse Aldrovandi (1522–1605). Entitled Discorso sopra alcuni animali quadrupedi per i quali si possono esprimere i 7 peccati capitali, literally ‘discourse about those animals through which it is possible to [symbolically] express the seven mortal sins,’ it was completed, according to an earlier copy (BUB Aldrov. 91, cc. 472r–482v), on 12 August 1578. The work was dedicated to Alessandro degli Orsi, a nobleman of the city and infantry commander in Hungary, who was honored in 1585 with the gran croce. This article suggests a reconstruction of lost decorations in one of the Orsi family mansions, either the Palazzo Orsi or the Villa Orsi. It also considers the moral implications of virtues versus vice represented by four-legged animals.