bluuebunny/crossref_metadata_2025 huggingface dataset:
The Christmas Eve Dialogue
Authors: Packman Andrew , Dole Andrew C.
Published: December 2023

Schleiermacher’s Christmas Eve Dialogue has long been viewed as providing a crucial window into Schleiermacher’s own life and theological commitments. Its vivid depiction of a Prussian family’s Christmas celebration provides insight into his social and historical context, and the characters’ reflections on the nature and meaning of Christmas shed light on Schleiermacher’s early christological views. The dialogical structure of the work has generated interesting puzzles of interpretation, including questions concerning the relationship of this work to the Platonic dialogues, with which Schleiermacher was heavily engaged at the time, and also questions concerning the relationship between Schleiermacher’s own views and those expressed by his characters. This chapter offers an overview of the Dialogue, engages three important trajectories in its reception history, and explores one possible avenue for extracting theological meaning from the work.
Schleiermacher and the Politics of Anglophone Religious Studies
Authors: Dole Andrew C.
Published: December 2023

Over the past generation a description of Schleiermacher as an “antireductionist,” “protectivist” theorist of “religious experience” has been in circulation within English secondary literature. In this chapter I reconstruct the history of the rise and promulgation of this portrayal. It seems fairly clear that the impetus for its development and circulation was the desire by some North American scholars to claim exclusive legitimacy for a “scientific” approach to the study of religion, and to fix an unbridgeable chasm between this and theological or “crypto-theological” approaches. Although this understanding of Schleiermacher now has few subscribers, I think the episode interesting because it is an example of the difficulties that scholars given to polarized thinking have in grappling with “mediating” positions like his in the historical record.
The Reformed Tradition
Authors: Rohls Jan
Published: December 2023

Schleiermacher was born into a Reformed family living in Breslau, and his father was a Reformed army chaplain in Silesia. Despite his support of the union between Lutherans and Reformed in one church in Prussia, he consistently regarded himself as a Reformed theologian. As an ordained minister of the Reformed church he signed the Reformed confessions valid at that time in Prussia. Yet he was also convinced that the main confessions for both the Lutherans and the Reformed did not stand in conflict but expressed a common Protestant spirit. The differences between Lutherans and Reformed in doctrine and ritual were no reason for the separation of the churches. The doctrinal differences concerning the Lord’s Supper, and closely connected with it Christology, played no decisive role for Schleiermacher, but regarding the doctrine of predestination he followed a Reformed line. The manner in which the Prussian king interfered in the order of worship contradicted his conviction that the church is a congregation independent from the state, its best constitution being the government by presbyteries and synods.
Friedrich Schleiermacher and the Postsecular
Authors: Robinson Matthew Ryan
Published: December 2023

The secular and the postsecular refer to sociopolitical challenges arising simultaneously due to the functional differentiation of modern societies and the co-presence of different religious groups in a single body politic. Friedrich Schleiermacher conducted groundbreaking empirical research on quite similar challenges in his own day, documented in his lectures on church geography and statistics. Furthermore, in both his early Letters on the Occasion and his mature lectures on a theory of the state, he outlined his views on peoplehood, religion, and the state in relation to social solidarity as well the consequences of this understanding for managing pluralism. If Schleiermacher’s empirical work is markedly innovative, his theory of the state leaves largely unclear how governance might adapt to shifting demographics and religious diversification.
Adverbs
Authors: Hengeveld Kees
Published: December 2023

The class of adverbs contains a large number of subcategories, ranging from adverbs of manner and degree to modal and illocutionary adverbs. What all adverbs have in common is that they modify a non-nominal head. This head may be lexical in nature, such as an adjective modified by a degree adverb, or syntactic, such as a full clause modified by an evidential adverb. In this chapter, adverbs are classified in terms of the types of head they modify, which will lead to a systematic classification of adverb classes that have been identified individually in the literature. It is furthermore shown that this classification provides the basis for a series of generalizations concerning the form and behaviour of classes of adverbs. These generalizations are formulated using the theoretical framework of Functional Discourse Grammar.
Word Classes in Mande Languages
Authors: Creissels Denis
Published: December 2023

The Mande language family includes about 70 languages which show a high degree of typological homogeneity in most respects. In particular, all Mande languages have extremely rigid word order patterns, which facilitates the use of distributional criteria in the recognition of word classes. By contrast, most of them (but not all) have very reduced inflectional morphology, which may favour the development of lexical polycategoriality, in particular as regards the distinction between nouns and verbs. In some Mande languages, all the lexemes that can be used as verbs can also be used in the same underived form as action nominalizations (but not vice versa: all Mande languages have lexemes that can only be used as nouns in their underived form). Mande languages also provide interesting data about the possible criteria that can be used to delimit classes of adjectives, adverbs, postpositions, or copulas. Finally, in Mande languages, the so-called predicative markers (a kind of auxiliaries) constitute a highly salient class of grammatical words expressing TAM, polarity, sometimes also subject indexation and distinctions related to transitivity and/or information structure.
Word Classes in Australian Languages
Authors: Louagie Dana
Published: December 2023

This chapter discusses word classes in Australian languages, covering the large Pama–Nyungan family as well as several smaller families. Australian languages are often described as generally lacking a noun–adjective distinction. This is true for part of the languages: they have a flexible class of nominals that can function both referentially and attributively. Other languages, however, have a distinct adjective class, which in some languages is both morphologically and distributionally defined, and in others only distributionally (e.g. by their position in the NP). Verbs, by contrast, are generally a clearly distinct class on morphosyntactic grounds, with minor morphological overlap with other parts of speech. In fact, several northern languages have two verbal word classes, viz. inflecting verbs and uninflecting verbs, which serve different predicational (and other) functions. Manner adverbs, finally, are also a distinct word class in most languages, although they may show morphological similarities with nominals (e.g. case marking) or verbs (e.g. TAM marking). Only some languages have lexemes that are flexible between adverbial and adjectival functions.
Word Classes in Eskimo–Aleut Languages
Authors: Mithun Marianne
Published: December 2023

It was once claimed that languages of the Eskimo–Aleut family contain just one lexical category: Nouns. The history of this claim is detailed in Sadock (1999) and further discussed in Woodbury (1985) and Mithun (2009, 2017b), among others. In fact, these languages show robust, distinct Noun and Verb categories (in addition to particles) at both the stem and word levels. Here the criteria that distinguish them are presented, then some subtleties reflecting deeper issues of lexical classification are examined, issues emerging from some major diachronic developments. First, the family is described; second, the features distinguishing Nouns and Verbs in the family are enumerated; third, the issue of flexibility is discussed; fourth, lexical subcategories are surveyed; fifth, the extension of nominalization to higher levels of structure is traced. This last step ultimately explains why it might have once been thought that there was just one lexical category.
Introduction
Authors: van Lier Eva
Published: December 2023

This introductory chapter presents the aims and scope of this handbook. It also outlines the contents of its constituent parts on fundamental issues, theoretical approaches, specific word classes, word classes across languages families, and across linguistic subdisciplines, respectively. In the process, this chapter identifies a number of overarching themes, which include the connection between language diversity and universals, the relationship between different types of word-class criteria (functional and formal), the nature of the category boundaries they define, and the (diachronic) link between major content word classes and grammatical word classes. A recurrent theme also concerns the methods that can be used to study the behaviour of word classes in and across languages and language users.
Word Classes in Formal Semantics
Authors: Winter Yoad
Published: December 2023

This chapter focuses on the formal semantics of nouns and its theoretical implications for other categories. This chapter introduces uniform semantic types of ‘extrinsic’ function–argument relations between categories in English and Warlpiri. By contrast, categories also have specialized ‘intrinsic’ semantic arguments. Other than exceptional cases like incorporation in Chamorro, only ‘intrinsic’ arguments can be modified in non-nominal categories. Nouns, by contrast, use their extrinsic argument for modification as well. Nouns also restrict quantificational domains, which are illustrated here by analysing unspecified nouns/verbs in Hebrew. The chapter discusses challenges to the idea that nouns are introducers of identity criteria, and review possible solutions. Lastly, the chapter reviews nominal reference to kinds and mass substances. This shows intimate relations between mass terms and property expressions, which affect the choices that languages make when manifesting property meanings as adjectival (most European languages) or nominal (Bisa, Hausa, and Basaá, among other languages).
Verbs
Authors: Letuchiy Alexander
Published: December 2023

This chapter focuses on verbs; their characteristic and distinguishing properties and phenomena. It shows that on the morphological level, verbs are characterized by paradigms with complex structure (often including several subparadigms with different set of categories and techniques of expression). The differentiation of inflection and derivation is often problematic, because some forms (e.g. infinitives) are necessary paired with elements intermediate between the root and the inflectional suffix. Another property of verbs is their ability to express many predicative categories. This fact is related to the opposition between finite and non-finite forms. Even if predicative categories are present in non-finite and embedded verb forms, they can have a special interpretation, based on their relation to the main (independent and finite) verb. Nonverbal predicates are less canonical than verbal ones, which is manifested in the fact that some predicative categories (such as tense and aspect) are sometimes not obligatory if the predicate is nonverbal. Finally, structures that do not have any explicit predicate (e.g. copula constructions) often behave syntactically in a noncanonical way.
Irish English in Today’s World
Authors: Hickey Raymond
Published: December 2023

At the beginning of the twentieth century the conception of Irish English as a distinctive variety of English began to emerge, with scholars dedicated to the subject active in the early decades. In the decades after the Second World War, further studies appeared in which the relationship of the Irish language to forms of English in Ireland loomed large, and most of the specific features of Irish English were traced to the historic language shift from Irish to English. Scholarship in the 1980s moved away from this ‘transfer’ position in favour of ‘retentionist’ views. At the same time, urban varieties formed a new focus, with different levels of language receiving increasing attention—above all pragmatics, a level on which Irish English differs clearly from other varieties. In addition, new corpora have been compiled which have broadened the database for linguistic investigations.
Mid-Ulster English and Ulster Scots
Authors: Maguire Warren
Published: December 2023

The northern Irish province of Ulster is home to two distinctive dialects not spoken elsewhere in Ireland: Mid-Ulster English (MUE) and Ulster Scots (USc). This chapter examines their historical origins, their linguistic features, and the relationship between them. Both MUE and USc have their origins in the Plantation of Ulster and associated settlements in the seventeenth and early eighteenth centuries. This period saw immigration of many English and Scottish settlers, which dramatically altered the province’s demographic and linguistic landscape giving rise to intense contact between Irish and dialects of English and Scots in a relatively small geographical area. This chapter explains how MUE and USc emerged through processes of language shift and new dialect formation which resulted from this contact. It furthermore discusses the common features shared by the two sets of varieties and outlines avenues for future research.
Urban English in Northern Ireland
Authors: Hickey Raymond
Published: December 2023

This chapter examines English as spoken in three main urban centres of Northern Ireland—Belfast, Derry, and Coleraine. The description and analysis of Belfast English begins with the nineteenth-century commentaries on vocabulary in the city, before moving forward to the social network studies carried out by James and Lesley Milroy in the 1970s and early 1980s. The insights of these seminal studies are discussed, including what they tell us about English in Northern Ireland as a whole. English in Derry contrasts with Belfast in a number of ways, not least in how it reacts to influence from the larger city and how some small but not insignificant differences in language use align along ethnic lines, correlating with Catholic or Protestant usage. English in Coleraine is also considered as an urban centre in which key linguistic variables, like (t), vary in their gender-specific realizations.
Politeness in Irish English
Authors: Vaughan Elaine
Published: December 2023

This chapter presents a concise overview of trends in the study of politeness, in order to contextualize selected key findings from studies that focus on (or at least include) considerations of politeness phenomena in Irish English. It considers how (im)politeness is conceptualized and explored in Irish English contexts, focusing on the ‘Irishness’ of language use in a variety of studies. These range from those situated in highly intimate domains of discourse such as the family to those which harvest language data from interaction amongst virtual strangers in Irish-based computer-mediated communication. The pragmatic turn in the study of Irish English coincided with the compilation of corpora representing the variety, and has resulted in corpus pragmatic research that illuminates the nature of (im)politeness across diverse interactional contexts in Irish English.
Irish Influence on Australian English
Authors: Musgrave Simon , Burridge Kate
Published: December 2023

Throughout the nineteenth century, people of Irish origin (including those born in Australia to Irish parents) were the second largest ethnic group in the Australian population, after those of English origin. This suggests that Irish people should have made a substantial contribution to Australian English, but the themes of this chapter will be that the contribution was rather small and very difficult to establish with any certainty. Research to date has uncovered surprisingly few lexical and grammatical items that can definitely be traced to the influence of Irish English; phonology remains an area in which Irish English may have had more of an impact on the emergence of Australian English, but the Irish contribution here has yet to be properly assessed. Here, we draw on a variety of different sources, including early linguistic commentary, to better understand the Irish impact on the formation of Australian English.
From Prototype to Genre
Authors: Schmidt Gabriela
Published: December 2023

The trajectory of Thomas More’s Utopia in early modern German showcases the book’s remarkable ability to adapt to very different sets of social and political circumstances. In responding to different aspects of Utopia’s multigeneric literary texture, the early modern German translations explored in this chapter helped to initiate reading traditions that gradually converged with other European responses into distinct generic strands of utopian writing. While the 1524 Basel version inserted the text into ongoing discussions of social, legal, and religious reform among Upper Rhinish urban and academic elites, Gregor Wintermonat’s 1612 translation coupled More’s text in a volume with Joseph Hall’s satirical anti-utopia Mundus Alter et Idem (Leipzig, 1613). Wintermonat’s publication is not only one of the first versions to clearly privilege the fictional aspects of More’s text over its non-fictional ones, it also helped generate a cluster of literary responses that gave later utopian fiction its characteristic satirical verve.
Utopia in Sixteenth-Century Italy
Authors: Shrank Cathy
Published: December 2023

This chapter examines Ortensio Lando’s anonymous translation of Utopia (1548)—the first posthumous translation and the first to include both books—and Francesco Sansovino’s revised translation of Book Two (1561), which appeared as the final part of Sansovino’s influential and much reprinted Del governo. As the chapter traces the role of the Bonvisis, a family of merchant bankers, in the posthumous stories of both Utopia and Thomas More, it highlights the importance of transnational networks and the way in which Reformation and Counter-Reformation shaped the reception of the book and its author. Where Lando’s translation, ushered into print by Anton Francesco Doni, is strongly associated with evangelical circles, Sansovino’s reworking—in a volume dedicated to Cardinal Pier Francesco Ferrero—aligns with religious orthodoxy. Further to that, the chapter explores the impact of seemingly small semantic changes, and the way in which Sansovino’s revisions reflect contemporary debates about the ‘proper’ form of written Italian.
Dialogue, Debate, and Orality in Ralph Robinson’s Utopias
Authors: Cavanagh Dermot
Published: December 2023

Ralph Robinson produced the first English translation of Utopia in 1551; the work was revised and reissued in 1556. This chapter will consider the style and mode of these two versions of More’s text. It emphasizes that both author and translator were citizens of London and that the primary intention of Robinson’s resourceful use of tone and idiom is to make Utopia’s civic concerns accessible. It also proposes that the revised edition expands, rather than constrains, its commitment to promoting debate on ‘the beste state of a publyque weale’. Robinson’s translation is both a major contribution to the dissemination of Utopia and a forceful articulation of its public concerns.
From Humanism to Enlightenment
Authors: Verhaart Floris
Published: December 2023

This chapter discusses the translation of Utopia by Nicolas Gueudeville (1652–1721?) and first published by Pieter van der Aa (1659–1733) in 1715. Following a summary of Gueudeville’s life and work and a description of the relevant political and cultural context, the chapter analyses the structure, themes, and (stylistic) characteristics of the translation, as well as its reception among eighteenth-century readers. It demonstrates that Gueudeville’s interpretation of More’s masterpiece was strongly influenced by the translator’s own concerns and interests. Stylistically, the translation is characterized by digressions and a predilection for bringing out burlesque and humorous elements in More’s work. For Pieter van der Aa, the translation constituted a relatively low-cost investment that offered reliable returns and a means of more prestigious multi-volume publications, such as the Thesaurus antiquitatum romanarum (1694–9) and an edition of Erasmus’ Opera Omnia (1703–6). In short, Gueudeville’s translation of Utopia was a product of his Huguenot background and Dutch publishing culture and popularized More’s work for an eighteenth-century readership.
More and the Republics of Plato
Authors: Hobbs Angela
Published: December 2023

More explicitly situates both Utopia and the Utopia it describes at least partly in relation to, and in playful competition with, Plato’s Republic. However, it is the main contention of this chapter that More’s knowledge of Greek, and understanding of Greek thought and methodologies, allows him to engage much more deeply with the Republic—and Plato’s corpus overall—than is immediately obvious from the surface resemblances, and that it richly repays the reader to consider afresh Plato’s not one but two imagined communities in the Republic, in order better to understand More’s own deliberately elliptical approach. Such a perspective enables the reader to see how the uses of serio-comedy and dialogue interconnect in Utopia to form an exploratory pedagogic work which is More’s deepest debt to Plato of all. Adapting Plato’s model, More converses with all those who have speculated and will continue to speculate on the nature of the ideally organized community, and the extent to which such communities either can or should be put into practice.
False Friends (and Their Uses)
Authors: Waithe Marcus
Published: December 2023

Many Victorian commentators were led astray in imagining Thomas More’s Utopia to be a kind of manifesto, and they often neglected its ludic elements. In exploring such distortions, this chapter refers to the semantic trap known in language learning as ‘the false friend’ or faux ami, which applies when ‘a word or expression in one language [ … ] has the same or similar form in another’ (OED). Rather than conceive these effects as matters of error, the focus is on their productive consequences. The last decades of the century witnessed an unusual convergence of Radical, conservative, and socialist elements whose affinities and divergences depended on matters not just lost, but also gained, in this broader sense of ‘translation’. In surveying this terrain, the chapter devotes close attention to the critical, imaginative, and editorial contributions of John Ruskin, William Morris, and H. G. Wells.
Not Just a Light-Hearted Joke
Authors: Nethercott Frances
Published: December 2023

This chapter charts the sequence of Russian translations of Utopia from the late eighteenth century to Brezhnev’s ‘stagnation’ in the 1970s. The backstories to the translations (1789, 1901, 1903, 1935, 1978) are revelatory of the shifts in the broader sociopolitical climate and instructive as contextual frames for understanding More’s chequered reception in tsarist Russia and his importance after 1917. Among the key points of reference are the strengthening of absolute rule in response to revolutions in continental Europe (1789 and 1848), the emergence of a nativist socialism in the second half of the nineteenth century, and the introduction of Marxism thereafter. The later translations also spotlight issues related to scholarship, university politics, and, from around 1900, the ethos of mass education, a phenomenon which would anchor Bolshevik policy. Translated, then, for the masses, Utopia entered the Soviet canon, its legacy secured as a template for the workers’ liberation.
Utopia, the Imperial Settler Utopia, and Imperial Settler Science Fiction
Authors: Weaver-Hightower Rebecca , Bajaber Musab
Published: December 2023

This chapter argues that Utopia is groundbreaking because it established the notion of ‘imperial settler utopias’ that influence attempted and fantasized manifestations of utopianism. Unlike settler utopias that are isolated and focused on inward development, imperial settler utopias—whether real or fictional—are settler colonies so entranced by their own ideals that they envision themselves as predestined to be dominant on the merit of their superiority. The interaction between fictional and attempted imperial settler utopias is cyclical. More’s Utopia influenced the development of real-world imperial settler utopian colonies and in return these colonies, combined with the legacy of Utopia, contributed to the rise of literary genres that extrapolate on imperial settler colonialism. These rising literary genres, again, continue to feed fantasies of imperialism. This chapter illustrates this cyclical interaction by, first, examining More’s influence on the development of settler colonies that eventually made up the United States. Then, it explains how, in return, the United States’ imperial settler utopian foundations led to the development of science fiction that fantasizes expansion into space as exemplified in Star Trek. These science fiction fantasies, again, affect actual attempts to explore space. This cycle of influence is one of the best examples illustrating More’s remarkable influence on the direction of history and literature since the publication of Utopia.
Away from the Ancestral Home
Authors: Siebers Johan
Published: December 2023

Ernst Bloch was credited by Adorno with having restored dignity to the idea of utopia in a century that saw modernity end in barbaric totalitarianism. In Bloch’s philosophy the sociopolitical origins of utopian thinking (Plato and especially More) form no more than the historically contingent starting point for an exploration of utopian motifs in all areas of human activity and even in the natural world. This chapter explores what happens to our conception of philosophy and philosophical method when we follow the expansive notion of utopia that animates Bloch’s work. The consequence is a radical reorientation in thought, which provides signposts for contemporary modes of thought that inherit and transform the cultural institution called ‘philosophy’. This chapter, therefore, is as much a study of the disruptive idea of utopia in modern philosophy as an exercise in utopian thinking.
‘Nothing is private anywhere’
Authors: Paul Joanne
Published: December 2023

This chapter seeks to shed light on the central message of More’s Utopia by examining it within the context of More’s concerns throughout his literary career. It maintains that one of More’s fundamental recurring arguments is the moral priority of what is held in common, which he connects to concepts such as death, pride, and politics in a variety of his works, both from the period before he wrote Utopia and after. With this reading, the reader is able to see the same themes at work in Utopia and form a better understanding of More’s intentions in writing it. In Utopia, More creates a fantastic island that represents the eternal ideals that he sees in operation beneath the worldly ‘stage play’ of pride and socially constructed inequality, not as a prescriptive programme, but as a reminder. Utopia, by this reading, operates like the memento mori of More’s earlier works, and is broadly consistent with the message of his later religious polemics.
The Religions of the Utopians
Authors: Sacks David Harris
Published: December 2023

In describing the diverse religions of the Utopians, Hythloday, More’s protagonist in Utopia, emphasized that in founding the island’s regime, Utopus had ‘prescribed that everyone may cultivate the religion of his choice’, and decreed against the use of coercion to impose religious uniformity. However, More’s later attacks on heretics as Lord Chancellor appear contrary to Utopian toleration. Did the Utopian rule ‘that no one should suffer for his religion’ represent More’s own view in 1516? Did he later change his mind? Or does Hythloday’s description already imply the existence of religious error among the Utopians and the possibility of sanctioning it? If the latter, on what grounds? This chapter, analysing More’s account of Utopian religions, reveals them to have been theologically flawed and sets strict limits to the toleration they could be afforded once Christianity was introduced among the Utopians.
Utopia and Travel Writing
Authors: Hadfield Andrew
Published: December 2023

This chapter explores how More makes use of the debates generated by the European discovery of the ‘New World’ (as well as older debates about other cultures) to represent the Utopians’ understanding of their interaction with other peoples, in particular, their thinking about colonial expansion. Raphael’s voyages with Amerigo Vespucci are represented as part factual and part mythical, enabling More to represent Utopia as an island that is in part real, in part fictitious. More’s strategies and the purpose of his fiction are various. At times Utopia is represented as a particular place, specifically Ireland, the island colonized by the English crown. The Utopians are sometimes seen as very similar to the peoples of the Americas, notably in their religious beliefs, as they lack revelation; in others, they are seen as akin to Europeans, working hard to solve problems and plan for the future. In the famous passage on sheep More uses the Utopians’ diligence to satirize what he saw as the idleness of the upper classes and their complacent exploitation of the people they should govern well.
Heritable changes of epialleles near genes in maize can be triggered in the absence of CHH methylation
Authors: Liu Beibei , Yang Diya , Wang Dafang , Liang Chun , Wang Jianping , Lisch Damon , Zhao Meixia
Published: December 2023

Trans-chromosomal interactions resulting in changes in DNA methylation during hybridization have been observed in several plant species. However, little is known about the causes or consequences of these interactions. Here, we compared DNA methylomes of F1 hybrids that are mutant for a small RNA biogenesis gene, Mop1 (Mediator of paramutation1), with that of their parents, wild-type siblings, and backcrossed progeny in maize (Zea mays). Our data show that hybridization triggers global changes in both trans-chromosomal methylation (TCM) and trans-chromosomal demethylation (TCdM), most of which involved changes in CHH methylation. In more than 60% of these TCM differentially methylated regions (DMRs) in which small RNAs are available, no significant changes in the quantity of small RNAs were observed. Methylation at the CHH TCM DMRs was largely lost in the mop1 mutant, although the effects of this mutant varied depending on the location of these DMRs. Interestingly, an increase in CHH at TCM DMRs was associated with enhanced expression of a subset of highly expressed genes and suppressed expression of a small number of lowly expressed genes. Examination of the methylation levels in backcrossed plants demonstrates that both TCM and TCdM can be maintained in the subsequent generation, but that TCdM is more stable than TCM. Surprisingly, although increased CHH methylation in most TCM DMRs in F1 plants required Mop1, initiation of a new epigenetic state of these DMRs did not require a functional copy of this gene, suggesting that initiation of these changes is independent of RNA-directed DNA methylation.
Stiffness-induced cancer-associated fibroblasts are responsible for immunosuppression in a platelet-derived growth factor ligand-dependent manner
Authors: Gamradt Pia , Thierry Kevin , Masmoudi Melissa , Wu Zhichong , Hernandez-Vargas Hector , Bachy Sophie , Antonio Tiffanie , Savas Berkan , Hussain Zainab , Tomasini Richard , Milani Pascale , Bertolino Philippe , Hennino Ana
Published: December 2023

Pancreatic ductal adenocarcinoma (PDAC) is associated with a vast stromal reaction that arises mainly from cancer-associated fibroblasts (CAFs) and promotes both immune escape and tumor growth. Here, we used a mouse model with deletion of the activin A receptor ALK4 in the context of the KrasG12D mutation, which strongly drives collagen deposition that leads to tissue stiffness. By ligand–receptor analysis of single-cell RNA-sequencing data, we identified that, in stiff conditions, neoplastic ductal cells instructed CAFs through sustained platelet-derived growth factor (PDGF) signaling. Tumor-associated tissue rigidity resulted in the emergence of stiffness-induced CAFs (siCAFs) in vitro and in vivo. Similar results were confirmed in human data. siCAFs were able to strongly inhibit CD8+ T-cell responses in vitro and in vivo, promoting local immunosuppression. More importantly, targeting PDGF signaling led to diminished siCAF and reduced tumor growth. Our data show for the first time that early paracrine signaling leads to profound changes in tissue mechanics, impacting immune responses and tumor progression. Our study highlights that PDGF ligand neutralization can normalize the tissue architecture independent of the genetic background, indicating that finely tuned stromal therapy may open new therapeutic avenues in pancreatic cancer.
IL-10 and IFN-γ as markers for early recognition of pediatric systemic lupus erythematosus complicated with macrophage activation syndrome
Authors: Qian Yanjie , Lu Meiping , Zheng Qi
Published: December 2023

Objectives

To compare the clinical and laboratory characteristics of pediatric-onset systemic lupus erythematosus (pSLE), pSLE with macrophage activation syndrome (MAS), and pSLE with recurrent MAS, and to find biomarkers for the differential diagnosis of these diseases.

Methods

Demographic, clinical, laboratory and radiological data were analysed for three groups of patients: 18 cases of pSLE with MAS, 48 age- and sex-matched cases of active pSLE without MAS and 40 age- and sex-matched cases of pSLE with inactive disease. One case of a 9-year-old girl with recurrent MAS as the primary manifestation of SLE also was recorded.

Results

IL-10 and IFN-γ levels were significantly higher in pSLE patients with MAS than in pSLE patients without MAS, and were significantly correlated with SLE and MAS laboratory features. Levels of IL-10 > 7.25 pg/ml had a high sensitivity and levels of IFN-γ  > 6.7 pg/ml had a high specificity for predicting MAS in pSLE. Constitutional symptoms were evident in the case of recurrent MAS in pSLE, and traditional immunosuppressive therapies were unable to prevent the next MAS episode.

Conclusion

Compared with pSLE and pSLE-MAS with a single episode, pSLE with recurrent MAS has different clinical manifestations and responses to treatment, requiring intensive studies to elucidate the underlying pathogenic mechanisms. Elevated serum levels of IL-10 and IFN-γ may be correlated with pSLE with MAS and can serve as serum biomarkers for pSLE with MAS.
Awake at the wheel: how auto technology innovations present ongoing sleep challenges and new safety opportunities
Authors: Rosekind Mark R , Michael Jeffrey P , Dorey-Stein Zachariah L , Watson Nathaniel F
Published: December 2023

Individuals and society are dependent on transportation. Individuals move about their world for work, school, healthcare, social activities, religious and athletic events, and so much more. Society requires the movement of goods, food, medicine, etc. for basic needs, commerce, cultural and political exchanges, and all of its dynamic, complex elements. To meet these critical daily demands, the transportation system operates globally and around the clock. Regardless of their role, a basic requirement for the individuals operating the transportation system is that they are awake and at optimal alertness. This applies to individuals driving their own cars, riding a bike or motorcycle, as well as pilots of commercial aircraft, train engineers, long-haul truck drivers, and air traffic controllers. Alert operators are a basic requirement for a safe and effective transportation system. Decades of scientific and operational research have demonstrated that the 24/7 scheduling demands on operators and passengers of our transportation system create sleep and circadian disruptions that reduce alertness and performance and cause serious safety problems. These challenges underly the longstanding interest in transportation safety by the sleep and circadian scientific community. An area currently offering perhaps the most significant opportunities and challenges in transportation safety involves vehicle technology innovations. This paper provides an overview of these latest innovations with a focus on sleep-relevant issues and opportunities. Drowsy driving is discussed, along with fatigue management in round-the-clock transportation operations. Examples of cases where technology innovations could improve or complicate sleep issues are discussed, and ongoing sleep challenges and new safety opportunities are considered.
Seasonal Dynamics and Distribution of Xylella fastidiosa in Infected Almond Trees
Authors: Zecharia Noa , Miri Vanunu , Dror Orit , Hatib Kamel , Holland Doron , Dani Shtienberg , Bahar Ofir
Published: December 2023

This research focused on studying the dynamics of the bacterial pathogen Xylella fastidiosa in almond trees across different developmental stages. The objective was to understand the seasonal distribution and concentration of X. fastidiosa within almond trees. Different tree organs, including leaves, shoots, branches, fruits, flowers, and roots, from 10 X. fastidiosa-infected almond trees were sampled over 2 years. The incidence and concentration of X. fastidiosa were determined using qPCR and isolation. Throughout the study, X. fastidiosa was consistently absent from fruits, flowers, and roots, whereas it was detected in leaves as well as in shoots and branches. We demonstrate that the absence of X. fastidiosa in the roots is likely linked to the inability of this isolate to infect the peach-almond hybrid rootstock GF677. X. fastidiosa incidence in shoots and branches remained consistent throughout the year, whereas in leaf petioles, it varied across developmental stages, with lower detection during the early and late stages of the season. Similarly, viable X. fastidiosa cells were isolated from shoots and branches at all developmental stages, but no successful isolations were achieved from leaf petioles during the vegetative and nut growth stage. Studying the progression of almond leaf scorch symptoms in trees with initial infections showed that once symptoms emerged on one branch, symptomless branches were likely already infected by the bacterium. Therefore, selectively pruning symptomatic branches is unlikely to cure the tree. This study enhances our understanding of X. fastidiosa dynamics in almond trees and may have practical applications for its detection and control.
Association of Mechanical Energy and Power with Postoperative Pulmonary Complications in Lung Resection Surgery: A Post Hoc Analysis of Randomized Clinical Trial Data
Authors: Yoon Susie , Nam Jae-Sik , Blank Randal S. , Ahn Hyun Joo , Park MiHye , Kim Heezoo , Kim Hye Jin , Choi Hoon , Kang Hyun-Uk , Lee Do-Kyeong , Ahn Joonghyun
Published: December 2023

Background

Mechanical power (MP), the rate of mechanical energy (ME) delivery, is a recently introduced unifying ventilator parameter consisting of tidal volume, airway pressures, and respiratory rates, which predicts pulmonary complications in several clinical contexts. However, ME has not been previously studied in the perioperative context, and neither parameter has been studied in the context of thoracic surgery utilizing one-lung ventilation.

Methods

The relationships between ME variables and postoperative pulmonary complications were evaluated in this post hoc analysis of data from a multicenter randomized clinical trial of lung resection surgery conducted between 2020 and 2021 (n = 1,170). Time-weighted average MP and ME (the area under the MP time curve) were obtained for individual patients. The primary analysis was the association of time-weighted average MP and ME with pulmonary complications within 7 postoperative days. Multivariable logistic regression was performed to examine the relationships between energy variables and the primary outcome.

Results

In 1,055 patients analyzed, pulmonary complications occurred in 41% (431 of 1,055). The median (interquartile ranges) ME and time-weighted average MP in patients who developed postoperative pulmonary complications versus those who did not were 1,146 (811 to 1,530) J versus 924 (730 to 1,240) J (P < 0.001), and 6.9 (5.5 to 8.7) J/min versus 6.7 (5.2 to 8.5) J/min (P = 0.091), respectively. ME was independently associated with postoperative pulmonary complications (ORadjusted, 1.44 [95% CI, 1.16 to 1.80]; P = 0.001). However, the association between time-weighted average MP and postoperative pulmonary complications was time-dependent, and time-weighted average MP was significantly associated with postoperative pulmonary complications in cases utilizing longer periods of mechanical ventilation (210 min or greater; ORadjusted, 1.46 [95% CI, 1.11 to 1.93]; P = 0.007). Normalization of ME and time-weighted average MP either to predicted body weight or to respiratory system compliance did not alter these associations.

Conclusions

ME and, in cases requiring longer periods of mechanical ventilation, MP were independently associated with postoperative pulmonary complications in thoracic surgery.

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New
The Effects of Residual Femoral Deformity on Computed Contact Mechanics in Patients Treated With In Situ Fixation for Slipped Capital Femoral Epiphysis
Authors: Aitken Holly D. , Yen Yi-Meng , Kiapour Ata M. , Sailer Wyatt M. , Holt Joshua B. , Goetz Jessica E. , Scott Elizabeth J.
Published: December 2023

Objective:

In situ fixation for treatment of slipped capital femoral epiphysis (SCFE) can stabilize the epiphysis and prevent further joint deformation but often leaves residual deformity that may adversely affect intra-articular contact mechanics. The purpose of this study was to investigate the relationship between residual deformity and contact mechanics in the post-SCFE hip.

Methods:

Patient-specific hip models were created for 19 patients with SCFE treated with in situ fixation. For each model, discrete element analysis was used to compute cumulative acetabular and femoral contact stress exposure during a walking gait cycle. Slip severity was evaluated for each patient using the two-dimensional Southwick angle and a novel three-dimensional (3D) assessment of multiplanar femoral deformity (3D slip angle).

Results:

Of the SCFE cases, 2/7 mild (Southwick angle ≤30 degrees) had peak cumulative femoral exposures equivalent to that of severe (Southwick angle ≥60 degrees) cases. Severe SCFE cases had higher peak (P = 0.015) and mean (P = 0.028) femoral contact stress exposure and lower cumulative femoral contact area (P = 0.003) than mild (Southwick angle ≤30 degrees) SCFE cases. Mean femoral contact stress exposure was also higher in severe SCFE cases than in moderate SCFE cases (P = 0.027). Acetabular and femoral contact mechanics metrics typically demonstrated stronger correlations with 3D slip angle than two-dimensional Southwick angle.

Conclusions:

Increased slip severity adversely impacts intra-articular femoral contact mechanics. Contact mechanics metrics demonstrate higher correlations with 3D slip angle, indicating that this novel measurement may better describe global deformity and its relationship to intra-articular mechanics; however, the modest strength of these correlations may also imply that global impingement-generating deformity is not the primary factor driving contact mechanics in the post-SCFE hip.

Clinical Relevance:

Greater slip severity adversely impacts contact mechanics in the post-SCFE hip. However, focal regions of high contact stress were seen even in mild SCFE deformities, suggesting some type of deformity correction should be considered even for mild slips to alleviate secondary impingement, address focal incongruities, and reduce osteoarthritis development/progression.
Standardized treatment protocols for hypertension: global availability, characteristics, and alignment with the hypertension guideline recommendations
Authors: Satheesh Gautam , Dhurjati Rupasvi , Huffman Mark D. , Rosende Andres , Rodgers Anthony , Prabhakaran Dorairaj , Ordunez Pedro , Jha Vivekanand , Salam Abdul
Published: December 2023

Background:

Hypertension control is suboptimal globally. Implementing evidence-based, simple, standardized treatment protocols (STPs) has been instrumental in effectively and efficiently improving treatment and control of hypertension. We aimed to identify, characterize, and critically appraise hypertension STPs.

Methods:

We defined STP as a series of steps for the pharmacological treatment of primary hypertension, with information on target population, BP threshold for treatment initiation, target BP, specific drugs/classes/doses, and follow-up frequency. STPs for adult patients were identified from the websites of relevant health organizations, Google search, and through expert consultations (until July 2023). STPs for secondary, gestational, or malignant hypertension or those that were templates/samples were excluded. Included STPs were critically appraised using HEARTS in the Americas Checklist for hypertension management in primary care and compared with the 2021 WHO hypertension management guideline recommendations.

Results:

Fifty STPs were identified. All STPs had a stepwise treatment approach, involved guideline-recommended first-line drugs, and 98% consisted of at least four steps. Majority (54%) recommended monotherapy with calcium channel blockers as first-line treatment. Only 44% STPs recommended treatment initiation with combination therapy, and 16% recommended single-pill combinations. Most (62%) had dose-intensification as the second step. Most (74%) STPs did not provide complete dosing information. Only one STP mentioned a target time for achieving BP control. On average, STPs scored a performance of 68% on the HEARTS Checklist.

Conclusion:

Several STPs are available globally; however, most of them have enormous scope for improvement through interventions aimed at alignment with the latest evidence-based guidelines and multistakeholder engagement.
ORBITAL COMPARTMENT SYNDROME AFTER PRIMARY SCLERAL BUCKLE SURGERY
Authors: Mei Frank , Tajran Jahan N. , Mohamed Mohamed R. , Patel Kishan G. , Wang Angeline L.
Published: December 2023

Purpose:

The aim of this study was to illustrate a patient with orbital compartment syndrome after scleral buckle placement that was successfully treated with canthotomy and cantholysis.

Methods:

This is an observational case report.

Results:

A 26-year-old man underwent a primary scleral buckle repair for a chronic rhegmatogenous retinal detachment. On postoperative day four, the patient presented to the emergency room with pain and increased intraocular pressure. Initial treatment with conservative intraocular pressure–lowering agents was unsuccessful. The patient was diagnosed with delayed orbital compartment syndrome and was successfully managed with lateral canthotomy and inferior cantholysis in addition to aggressive steroid and antibiotic medical management.

Conclusion:

After scleral buckle placement with sub-Tenon anesthesia block, there may be a delayed presentation of orbital compartment syndrome. Recognition and management of this rare complication is important for preventing irreversible blindness.