bluuebunny/crossref_metadata_2025 huggingface dataset:
The Sociolinguistic Profile of English at the Grassroots Level: A Comparison of Northern and Western Uganda
Authors: Isingoma Bebwa
Published: September 2021

This chapter delineates the sociolinguistic profile of two categories of speakers of English in Uganda, i.e. market vendors and bodaboda (motorcycle taxi) riders, who may voluntarily or incidentally use English, given the nature of their trade, which requires them to interact with customers who may not speak their L1 or an indigenous language of wider communication in their region. Using participant observations and recorded semi-structured interviews, the study details the quotidian linguistic behaviour of 30 grassroots users of English, their attitudes towards the use of English and their verbal repertoires. The results indicate different linguistic behaviours, with Northern Uganda recording more inclination to the use of English than Western Uganda, as well as displaying more positive attitudes towards its use and a richer verbal repertoire. Also, English at the grassroots depicts many of the innovative features present among acrolectal speakers of Ugandan English, that is, the speakers of grassroots English in Uganda cannot replace the innovative norms developed by the acrolectal speakers with or example Standard British English norms. Ugandan English may therefore be said to be both norm-developing as well as norm-providing in that the acrolectal sub-variety provides the grassroots sub-variety with the norms it has developed.
Access to English and the Englishes of the Disadvantaged: Examples from Uganda and South Africa
Authors: Meierkord Christiane
Published: September 2021

This chapter offers a comparative look at the histories of English in Uganda and South Africa and a concise description of what access to both formal and informal acquisition of English has been like in the two countries, post-independence and in the 2000s. Against this background, excerpts of data obtained from grassroots speakers in the Cape Town and Kampala regions, whose work and businesses involve the regular use of English, are presented and analysed qualitatively. The results reveal how access to English and to formal education in South Africa and Uganda has shaped the Englishes of those speakers of English who are not as advantaged as others. They indicate that the utterances of older South Africans reflect their informal acquisition of English through interaction with lower class whites and contain features typically associated with learners, second language varieties, and pidginised forms of English. Younger speakers who have attended English-medium schools post-Apartheid as well as the Ugandan speakers seem more conscious of mistakes and correct themselves. The chapter finishes with an outlook into how grassroots speakers can (and need to) be integrated in models of world Englishes.
The Responsibility to Understand
Authors: George Theodore
Published: September 2021

In this chapter, I build on current post-Gadamerian scholarship in hermeneutics to argue that Gadamer’s attempt to advance Heidegger’s ontological turn in hermeneutics is oriented by the question of responsibility. In his major work Truth and Method, Gadamer suggests that his attempt to advance Heidegger’s ontological turn in hermeneutics concerns a further turn toward language. I argue that while Gadamer’s concern for this further turn toward language is unassailable, his attempt to advance Heidegger’s ontological turn is also crucially oriented by Heidegger’s call in his Letter on Humanism for an original ethics. In consequence, as I show, Gadamer’s philosophical hermeneutics not only includes considerations in practical philosophy but must itself be understood as what Heidegger described as an original ethics.
The Capacity for Displacement
Authors: George Theodore
Published: September 2021

The purpose of Chapter 2 is to examine Gadamer’s elucidation of the hermeneutical experiences of understanding and interpretation in terms of original ethics. In this, I argue that the responsibility to understand is not foremost a responsibility to reach agreement or achieve correct knowledge of something. Rather, the responsibility to understand is a responsibility to cultivate and enact what I refer to as a capacity for displacement, that is, a capacity to put one’s prejudices—and thus oneself—into question, to remain open to the new in the face of such self-interrogation, and to come to understand things and oneself otherwise through it.
Actors’ Effigies and Photo-Portraits
Authors: Popenhagen Ron J. , Popenhagen Ron J.
Published: September 2021

Disguise and Masquerade in Chapter Five features body forms and constructions during the interwar years in Weimar, Paris, Moscow and Brussels. Instances of the human body as scenographic material increase in number and intensity as modern dance and theatre diminish the differences between and actor and the object. Experimentation at the Bauhaus, particularly by Oskar Schlemmer, is detailed in ‘Ballerina Objects and Mechanical Pierrots’. Further adaptations of figures from the commedia dell’arte push the concept of ‘kinetic painting’ and choreographic text to new levels (as with dancer-artist Akarova). Advances in self-portrait photography as identity study, particularly by women artists like Arndt, Cahun and Krull, engage masking in new interpretations of the être-objet (Dalí). Additional modernist photographs of Dora Maar, Man Ray and others are analysed. Elements of Dada, Expressionism and Futurism appear in this collection of masquerades. Magritte’s provocative images of woman and man with fabric-covered bodies and faces tilts modernist disguising to the heart of Surrealism.
Reactive and Aggressive Years of the Akp
Authors: Öztürk Ahmet Erdi
Published: September 2021

This chapter aims to read the AKP period of Turkey in light of a combination of domestic and foreign policies, with religion at the forefront. In these two chapters, the concept of ‘state of exception’ is employed to understand the authoritarian ethno-nationalist Sunnification of Turkey under AKP rule. Indeed, throughout the chapters the new positions of state institutions such as Diyanet, the role of the Gülen Movement, the role of Ahmet Davutoğlu in the new Turkish foreign policy and the leadership of Erdoğan constitute the priorities, since these are the main determinants in an understanding of the relations between the Balkans and Turkey since the early 2000s.
Introduction
Authors: Öztürk Ahmet Erdi
Published: September 2021

The previous pages can be encapsulated in four claims that are directly and indirectly related to Turkey’s policy preferences on the Balkan Peninsula. By focusing on these claims, this last part of the book sets out to explain the complicated relationship among state identities, power and religion, and their impact on foreign policy in the case of Turkey under AKP rule....
Service to the Global Ummah
Authors: Öztürk Ahmet Erdi
Published: September 2021

Under the shadow of these observations and findings, the AKP has realised that Turkey’s Western-oriented laik foreign policy has not been serving the new interests of Turkey, and so it aims to establish deeper relations with the Balkan countries, but particularly with the Muslims of these countries. Turkey has in fact been preferring to serve the Ummah, instead of expanding relations with all components of the Balkans, in spite of the fragile economic conditions prevailing in the region. Even though the socio-political elites of the host countries are pleased with these initiatives, they are at the same time suspicious. Hence, this mostly single-sided and religion-oriented investment approach is one of the significant indicators of how its preferences make Turkey an ambiguous power in the region.
Interfering in the Internal Affairs of Host Countries
Authors: Öztürk Ahmet Erdi
Published: September 2021

The power and influence of the Gülen Movement is another factor in the reactions of the case countries, but the main determinant is the response capacities of the countries in question. In this regard, the Bulgarian state seems to have the greatest capacity to respond directly to the problems exported from Turkey. It is a member state of the EU, which could intervene to block some of Turkey’s demands. On the other hand, the Bulgarian authorities are aware that without the Diyanet’s financial support there may be serious issues among the country’s Muslim population. Therefore, it has been trying to frame the issues in a delicate balance.
Conclusion The New Turkey in the Balkans: An Ambiguous Actor?
Authors: Öztürk Ahmet Erdi
Published: September 2021

Drawing on over two years of fieldwork and more than 120 semi-structured elite interviews in Turkey and the Balkans, this book seeks to illuminate a neglected aspect of Turkey’s relations with its Balkan neighbours, in the context of the broader shift in Turkish domestic and foreign policy under the AKP from a realist-secular orientation to an ambiguous coercive Sunni Islamic one. It explains the complex relations between religion (Islam) and state identity, and their reflection in state power. In order to analyse how these concepts have been utilized and how they been received locally, this book uses as primary sources both Turkish and local actors in the three country cases: Republic of Bulgaria, Republic of North Macedonia and Republic of Albania. This part summaries all of these points
Introduction
Authors: Mee Sharon Jane
Published: September 2021

The introduction establishes the concept of the cinematic pulse, outlining the limitations in Rosalind E. Krauss’s theory of the pulse and the need for an energetic understanding of cinema. It describes ways by which the pulse may be distinguished from rhythm. Definitions of key concepts that will be developed throughout the book are provided, including dispositif, aisthesis, and sovereign operation. By tracking body horror scholarship through the work of Carol J. Clover and Linda Williams, the argument for finding the pulse in horror films that focus on the body is outlined.
Apprehension Engines: Defining a New Wave of Art-Horror Cinema
Authors: Church David
Published: September 2021

This chapter introduces the term “post-horror” and positions it as an emergent cycle within the longer traditions of art cinema and specifically art-horror cinema. The chapter argues that post-horror films are distinguished by their minimalist aesthetic, their use of epistemic and narrative ambiguity, and their de-sensationalized approach to genre conventions. Prioritizing atmospheres of lingering dread and physical/emotion isolation instead of monsters and jump scares, these films evince a tonal distance from more mainstream genre expectations. Hence, by crossing over from the arthouse/festival circuit to multiplexes, these films’ capacity to generate strong negative affects which do not easily translate into populist entertainment has engendered both outsized acclaim from high-minded critics and backlash from more casual viewers.
Felicia Hemans and the Birth of the Mass-Market Woman Poet
Authors: Easley Alexis
Published: September 2021

This chapter focuses the career of Felicia Hemans, one of the first women writers to achieve widespread fame as a mass-market poet. I begin with an overview of the revolution in print that corresponded with the span of Hemans’s career, 1808 to 1835. While Hemans’s poems might have made their first appearance in books or periodicals priced at one shilling or more, they were among the most frequently reprinted content in periodicals and newspapers aimed at broad audiences that included working-class and lower-middle-class readers. In the second part of this chapter, I use Hemans’s poem ‘The Better Land’ as a case study for exploring how the practice of reprinting enabled the dissemination of her work to mass-market audiences and niche readerships. In the third section of this chapter, I explore the history of American reprintings of Hemans’s poetry, highlighting how she negotiated the lack of international copyright protection for British authors in order to harness new markets abroad. I close the chapter by exploring a posthumously published poem, ‘To My Own Portrait.’ Its circulation in memorials after Hemans’s death tells us much about emergent visual print culture, which defined the ‘poetess’ as both a celebrity author and a pictorial image.
‘Drama[s] of exact observation’: Spark and the Nouveau Roman
Authors: Bailey James
Published: September 2021

Concentrating on the development of her fiction during the decade spanning 1960 to 1970, this chapter traces the evolving relationship between Spark’s novels and the style and ethos of the nouveau roman. It focuses in particular on Spark’s inventive appropriation of what she termed ‘the drama of exact observation,’ as derived from the meticulous, externalised narration characteristic of the work of one of the key practitioners of the nouveau roman, Alain Robbe-Grillet. Although critical analysis of Spark’s relationship with the anti-novel has largely been restricted to a small selection of overtly experimental novels written by the author during the early 1970s, this chapter demonstrates that the nouveau roman also served as a crucial influence on earlier works including 1960’s subversive social satire, The Ballad of Peckham Rye, as well the uncharacteristically expansive sociopolitical novel, The Mandelbaum Gate, published in 1965. Both texts, the chapter argues, reveal Spark actively interrogating the alternatively humorous and horrifying possibilities of the nouveau roman as a mode of writing. The chapter culminates with a discussion of The Driver’s Seat as Spark’s Spark’s most direct – and self-reflexive – encounter with the anti-novel.
Leaving the Hothouse
Authors: Bailey James
Published: September 2021

This concluding chapter presents a detailed examination of Spark’s most outlandish work of metafiction, The Hothouse by the East River, as a means of uniting the various, interrelated strands of literary experimentation, satire, subversion and social critique discussed over the course of the preceding chapters. Like The Driver’s Seat almost immediately before it, Hothouse stages the operation and gradual deconstruction of a masculine ideal of all-knowing omnipotence; its protagonist, Paul, spirals into impotent obsession when he finds himself unable to decipher the impenetrable mystery concocted by his ghostly wife, Elsa. Before this point, Paul has enjoyed exploiting the kind of manipulative authority exhibited by the likes of The Public Image’s Frederick Christopher, Not to Disturb’s Baron Klopstock, The Ballad of Peckham Rye’s Mr Druce, and Doctors of Philosophy’s Charlie Delfont. Akin to the female characters in those texts (Annabel Christopher, Baroness Klopstock, Merle Coverdale and Leonora Chase, most notably), Elsa has come to languish within a narrow, preconstructed role, before seizing her opportunity, as Leonora and Annabel do, to abandon it entirely.
This chapter concludes with a discussion of Spark’s best-known novel, The Prime of Miss Jean Brodie, before reflecting critically on the aims and achievements of the present study.
‘Wonderful things’: Howard Carter, Literary Genre and Material Intertextuality
Authors: Dobson Eleanor
Published: September 2021

This chapter considers the generic and material conventions of writings by Egyptologists alongside those of fiction, observing a multifaceted intertextual relationship between these forms. I outline how book designs incorporating gilt mimicked Egyptian artefacts, capitalising upon the sensationalism with which discoveries of gold relics were reported whereby these objects were coded as ‘treasure’. Further to the physical parallels between Egyptological writing and fiction, this chapter charts mutual textual influences. With particular focus on the first two volumes of The Tomb of Tut·ankh·Amen (1923; 1928), it compares the published version of accounts of discovery to Howard Carter’s original notes recorded at the time of the excavations, shedding light on a revised and romanticised narrative, and paying attention to both the atmospheric effects of Harry Burton’s photographs as well as the tangible influence of the novelist Percy White. Considering, too, the account of the death of Carter’s canary published in Pearson’s Magazine as ‘The Tomb of the Bird’, it discusses Carter’s conflicted relationship with the notion of the pharaoh’s curse, proposed by some as being behind the death of Carter’s patron, the fifth Earl of Carnarvon – by this time a familiar trope of Gothic fiction.
Servitude
Authors: Taylor Dan
Published: September 2021

Chapter 1 explores why we are not free, and what passivity means for us individually, and with others. It begins with servitude, under the premise that any philosophical commonplace like the mind’s freedom being through contemplating truths is insubstantial, unless it can also account for why minds are not free, what their servitude consists of, and what prevents human beings from easily achieving such a freedom. The first chapter is principally concerned with the TTP, and broadly considers servitude as a state of being possessed by harmful ideas. It is both an internal state and a more extensive one than traditional readings admit, and the chapter assesses its links to fortune, superstition, and to political domination. Servitude is a state where disempowerment is made meaningful and rewarding, rather than intolerable, and this problem is used to connect ethical freedom to political rights, as well as to questions of fortune, prejudice and superstition which impede the circulation and understanding of true ideas.
‘Something of an Autobiography’
Authors: Dabashi Hamid
Published: September 2021

In this chapter I wish to place the short but exceptionally rich and important life of Jalal Al-e Ahmad (1923–69) in the context of the most vital events of his deeply consequential life. Born during the waning years of the Qajar dynasty (1789–1925) and dead at the age of forty-six, soon after the June 1963 uprising of Ayatollah Khomeini against Mohammad Reza Shah, Al-e Ahmad lived an enduringly influential life, leaving his indelible mark on the fate of his homeland. His intellectual and political career began at a very young age in his late teens, and he died of a sudden stroke at the prime of his literary and intellectual productivities.
Translating the World
Authors: Dabashi Hamid
Published: September 2021

A detailed consideration of Al-e Ahmad’s translations of mostly European sources. What were these translations, from what originals, for what reasons, and what do they tells us about Al-e Ahmad's state of mind?
Backchannel Communications: Talking to the Enemy Behind the Scenes
Authors: Kadıoğlu İ. Aytaç
Published: September 2021

The nature of political, non-violent peace efforts resulted in over-motivation on official negotiations between conflicting parties and so caused an intention to limit peace processes with these negotiations only. This chapter includes secret communication channels into conflict resolution processes as the pre-negotiation stage and so draws a broader framework for peacemaking. The influence of these track one-and-a-half efforts between the principle armed protagonists, namely the British and Turkish governments on the one hand, the IRA and PKK on the other, are the focus of the research. The chapter reveals that while the pre-negotiation stage began during the early 1970s and lasted until the early 1990s when the Northern Irish parties and British government commenced official negotiations, it was between the 1980s and early 2010s in the Turkish case. It investigates backchannel communications in twofold: (1) Direct talks which bring representatives of disputing parties together in a secret location, (2) indirect communications which are achieved through communication chains built by one or more chains. It is rounded off with a comparison of the two cases regarding the role of these factors in de-escalating the conflict or obstructing peacemaking attempts.
Lamia, Isabella, The Eve of St Agnes, And Other Poems (1820) as a Unified Volume
Authors: White Robert
Published: September 2021

Whereas most books on Keats’s poetry, including most editions of his works, present and deal with individual poems singly and in the chronological order and biographical contexts of their composition with an implicit aim of demonstrating Keats’s development from ‘juvenilia’, to ‘maturity’ and giving priority to the Odes, I shall instead focus on the likelihood that Keats consciously shaped the contents into a considered structure and order, in order to create a unified whole. Recognising this provides a fresh significance and perspective to the individual poems, allowing them to be read in interrelated ways, instead of as individual works interpreted in the light of when and where they were composed. The one important qualification I shall argue for is that there is evidence that Keats intended ‘Ode to Melancholy’ to be the final poem in the collection, and that he regarded the inclusion of ‘Hyperion: A Fragment’ as a publisher’s decision with which he did not necessarily agree.
Melancholy: From Medical Condition to Poetic Convention
Authors: White Robert
Published: September 2021

Keats was a connoisseur of melancholy in all its manifestations and reinventions, deriving from the ancient medical ailment, the Renaissance ‘Epidemical disease’ (Robert Burton’s phrase) epitomised in Shakespeare’s Hamlet and Jaques, to Romantic poetic cult. In a literal sense his childhood years were spent under Melancholy since, as Nicholas Roe notes, opposite the Swan and Hoop inn and livery stables in Moorgate was Bedlam presided over by Caius Cibber’s twinned statues, ‘Melancholy Madness’ and ‘Raving Madness’. When he came to study medicine and walk the wards in Guy’s Hospital, the living embodiments were to become all too real for him. Keats’s retentive memory, Roe further suggests, carried this very image in his mind to re-emerge as the slumped and despondent fallen Titans in Hyperion. The history of melancholy is vast and complex, and to keep the proportions of this book under control I present only the briefest of summaries here, in preparation for more detailed inspection of Keats’s markings and annotations on his copy of Robert Burton’s The Anatomy of Melancholy, followed by a melancholy-centred analysis of the 1820 collection of poems.
Introduction
Authors: Schuett Robert
Published: September 2021

What does it mean to say that, from first to last, Kelsen’s political thinking was focused on the real You and Me? Why such a hard-edged defence of Kelsen as a man of political realism for our time? The introductory chapter situates the book’s central theme against the current wave of substantial interest in Kelsen’s legal philosophy and democratic theory. It elaborates on the book’s political methodology of doing combined intellectual biography and comparative conceptual analysis, and explains its combative writing style. This scene-setter suggests forgetting the jurist for a little while, and outlines how the book’s five analytical chapters bring Kelsen’s life and thought into a productive tension with today’s Schmittians and conventional views of foreign-policy realism.
Kelsen’s Enemies
Authors: Schuett Robert
Published: September 2021

Why is Kelsen such a consequential and controversial, perhaps even misunderstood, political thinker and actor? Who wants to make us believe that Kelsen was a naïve idealist dreaming up a Kantian peace and throwing white sand at battle cruisers? The chapter is a rebuttal of the many clichés propounded by Schmittians and the other pseudo-realists that are thrown at Kelsen and the project of a Pure theory of law, state, and international legal order. The fact that the FBI was after Kelsen as an alleged communist is as ridiculous as it is tragic, and even two of his own students, Hans J. Morgenthau and John H. Herz, did not seem to understand legal positivism’s cold analysis of political and international life. The same goes for the fact that Kelsen was, actually, a tough Freudian human nature realist who turned the tables on natural law ideologues. Who’s naïve now?
Kelsen’s Freudian Moment
Authors: Schuett Robert
Published: September 2021

What makes Kelsen argue that we are no Kantian angels? Why is the Kelsenian state a centralised coercive order understood in terms of law as a system of norms? The chapter continues the exploration of Kelsen’s milieu and expands on it to examine how the impact of Freud’s psychology and philosophical anthropology on Kelsen’s thought relating to the dynamics of human nature, society, and the political as a problem of authority and obedience is shown to be real and profound. To zoom in on the core of Kelsen’s philosophy and political theory is to recapture a breathtakingly rich and realistic account of You and Me that makes clear, in the best of the Realist tradition, that where there is Us, the struggle for power and conflicts of interests are here to stay.
Religious Drama and the Polemics of Conversion in Madrid
Authors: Jouve Martín José R.
Published: September 2021

16th- and 17th- century Spanish theatre became a vehicle through which to explore the politics and polemics of conversion in a multicultural empire that presented itself as the champion of Catholic orthodoxy. As the chapter suggests, the appeal of many of these works was not their didactic nature, but rather their playful recreation of the fundamental tensions that surrounded the idea of religious and social conversion in early modern Spain.
Coda: Performing Conversion in an Early Modern Future
Authors: Wittek Stephen
Published: September 2021

This chapter considers similarities between early modernity and the present era in terms of theatricality and practices of conversion. Examples of conversional practices from the past hundred years include the forced conversion of Aboriginal children in Canadian residential schools, the so-called ‘conversion therapies’ purporting to ‘cure’ LGBTQ people, and the conversions imposed on Jews by entrenched structures of anti-Semitism. In readings of three 21st Century plays that explore these issues, the author emphasizes the unique ability of drama to bring critical analysis and insight to the performative nature of conversional social practices. His study asserts the centrality of dramatic and social performance to the ongoing evolution of conversional phenomena, drawing lines of connection between the theatrical representations explored in the preceding chapters and similar offerings in our own age.
Preface and Acknowledgements
Authors: Lev Efraim
Published: September 2021

In this chapter the necessary introductory issues are presented – namely rationale and history of research, chronology, geography and acknowledgments.
Prosopography of Jewish Medical Practitioners
Authors: Lev Efraim
Published: September 2021

The beginning of the third chapter discusses and fully present 496 biographies of Jewish physicians, followed by the biographies of 111 Jewish pharmacists (apothecaries, perfumers and druggists). It also deals with related issues, such as potion makers and commercial aspects of drugs. Making up a third group are the dynasties of Jewish practitioners, a phenomenon that will be explained and discussed. Forty-nine dynasties consisting of 139 practitioners will be presented, including the biographies of the members and in most cases a chart of the family tree, along with detailed discussion of the dynasties, their role in the Jewish communities and their relationship with the Muslim administrations and rulers throughout the relevant periods.
Impact of Mergers and Acquisitions on Operational Performance of Islamic Banking Sector
Authors: Ullah Nazim , Nor Fauzias Mat , Seman Junaidah Abu
Published: September 2021

Merger and acquisition (hereafter MA) are the business expansion strategy. Islamic bank is the niche banking sector compared to its peers while it is categorized as too small to succeed. The paper aims to analyze the impact of MA on the operational performance of the Islamic banking sector. This study employs empirical research methods, namely cross-sectional pooled regression and panel data regression to analyze a set of samples consisting of 10 Islamic banks involved in MA from 6 countries, drawn from the International Monetary Fund (IMF), World bank, Ficth Connect, and Bloomberg over the years of 2009Q1to 2018Q4. The operational performance is estimated using accounting-based measures while the Herfindahl-Hirschman Index (HHI) and the concentration ratio (CR) are applied to signify market structure. Total assets, total deposits, and operating income variables are used to represent bank size. The findings indicate that bank size shows a negative impact on operational performance. While the segregated level of bank size which is larger banks and concentrated market structure has a greater impact on the operational performance of Islamic banks in the post-MA period. The paper concludes by discussing policy implications for policymakers and academicians for having the strategic decision on the MA deal and further research.
Systematic Characterization of Novel Immune Gene Signatures Predicts Prognostic Factors in Hepatocellular Carcinoma
Authors: Xu Dafeng , Wang Yu , Wu Jincai , Zhang Yuliang , Liu Zhehao , Chen Yonghai , Zheng Jinfang
Published: September 2021

Background: The prognosis of patients with hepatocellular carcinoma (HCC) is negatively affected by the lack of effective prognostic indicators. The change of tumor immune microenvironment promotes the development of HCC. This study explored new markers and predicted the prognosis of HCC patients by systematically analyzing immune characteristic genes.

Methods: Immune-related genes were obtained, and the differentially expressed immune genes (DEIGs) between tumor and para-cancer samples were identified and analyzed using gene expression profiles from TCGA, HCCDB, and GEO databases. An immune prognosis model was also constructed to evaluate the predictive performance in different cohorts. The high and low groups were divided based on the risk score of the model, and different algorithms were used to evaluate the tumor immune infiltration cell (TIIC). The expression and prognosis of core genes in pan-cancer cohorts were analyzed, and gene enrichment analysis was performed using clusterProfiler. Finally, the expression of the hub genes of the model was validated by clinical samples.

Results: Based on the analysis of 730 immune-related genes, we identified 64 common DEIGs. These genes were enriched in the tumor immunologic related signaling pathways. The first 15 genes were selected using RankAggreg analysis, and all the genes showed a consistent expression trend across multi-cohorts. Based on lasso cox regression analysis, a 5-gene signature risk model (ATG10, IL18RAP, PRKCD, SLC11A1, and SPP1) was constructed. The signature has strong robustness and can stabilize different cohorts (TCGA-LIHC, HCCDB18, and GSE14520). Compared with other existing models, our model has better performance. CIBERSORT was used to assess the landscape maps of 22 types of immune cells in TCGA, GSE14520, and HCCDB18 cohorts, and found a consistent trend in the distribution of TIIC. In the high-risk score group, scores of Macrophages M1, Mast cell resting, and T cells CD8 were significantly lower than those of the low-risk score group. Different immune expression characteristics, lead to the different prognosis. Western blot demonstrated that ATG10, PRKCD, and SPP1 were highly expressed in cancer tissues, while IL18RAP and SLC11A1 expression in cancer tissues was lower. In addition, IL18RAP has a highly positive correlation with B cell, macrophage, Neutrophil, Dendritic cell, CD8 cell, and CD4 cell. The SPP1, PRKCD, and SLC11A1 genes have the strongest correlation with macrophages. The expression of ATG10, IL18RAP, PRKCD, SLC11A1, and SPP1 genes varies among different immune subtypes and between different T stages.

Conclusion: The 5-immu-gene signature constructed in this study could be utilized as a new prognostic marker for patients with HCC.
Organoid Technology: A Reliable Developmental Biology Tool for Organ-Specific Nanotoxicity Evaluation
Authors: Prasad Minakshi , Kumar Rajesh , Buragohain Lukumoni , Kumari Ankur , Ghosh Mayukh
Published: September 2021

Engineered nanomaterials are bestowed with certain inherent physicochemical properties unlike their parent materials, rendering them suitable for the multifaceted needs of state-of-the-art biomedical, and pharmaceutical applications. The log-phase development of nano-science along with improved “bench to beside” conversion carries an enhanced probability of human exposure with numerous nanoparticles. Thus, toxicity assessment of these novel nanoscale materials holds a key to ensuring the safety aspects or else the global biome will certainly face a debacle. The toxicity may span from health hazards due to direct exposure to indirect means through food chain contamination or environmental pollution, even causing genotoxicity. Multiple ways of nanotoxicity evaluation include several in vitro and in vivo methods, with in vitro methods occupying the bulk of the “experimental space.” The underlying reason may be multiple, but ethical constraints in in vivo animal experiments are a significant one. Two-dimensional (2D) monoculture is undoubtedly the most exploited in vitro method providing advantages in terms of cost-effectiveness, high throughput, and reproducibility. However, it often fails to mimic a tissue or organ which possesses a defined three-dimensional structure (3D) along with intercellular communication machinery. Instead, microtissues such as spheroids or organoids having a precise 3D architecture and proximate in vivo tissue-like behavior can provide a more realistic evaluation than 2D monocultures. Recent developments in microfluidics and bioreactor-based organoid synthesis have eased the difficulties to prosper nano-toxicological analysis in organoid models surpassing the obstacle of ethical issues. The present review will enlighten applications of organoids in nanotoxicological evaluation, their advantages, and prospects toward securing commonplace nano-interventions.
Characterization of Molecular Heterogeneity Associated With Tumor Microenvironment in Clear Cell Renal Cell Carcinoma to Aid Immunotherapy
Authors: Zhong Weimin , Li Yinan , Yuan Yichu , Zhong Hongbin , Huang Chaoqun , Huang Jiwei , Lin Yao , Huang Jiyi
Published: September 2021

Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer and has strong immunogenicity. A systematically investigation of the tumor microenvironment (TME) in ccRCC could contribute to help clinicians develop personalized treatment and facilitate clinical decision-making. In this study, we analyzed the immune-related subtype of ccRCC on the basis of immune-related gene expression data in The Cancer Genome Atlas (TCGA, N = 512) and E-MTAB-1980 (N = 101) dataset, respectively. As a result, two subtypes (C1 and C2) were identified by performing non-negative matrix factorization clustering. Subtype C1 was characterized by increased advance ccRCC cases and immune-related pathways. A higher immune score, stromal score, TMB value, Tumor Immune Dysfunction and Exclusion (TIDE) prediction score, and immune checkpoint genes expression level were also observed in C1. In addition, the C1 subtype might benefit from chemotherapy and immunotherapy. The patients in subtype C2 had more metabolism-related pathways, higher tumor purity, and a better prognosis. Moreover, some small molecular compounds for the treatment of ccRCC were identified between the two subtypes by using the Connectivity Map (CMap) database. Finally, we constructed and validated an immune-related (IR) score to evaluate immune modification individually. A high IR score corresponded to a favorable prognosis compared to a low IR score, while more advanced tumor stage and grade cases were enriched in the low IR score group. The two IR score groups also showed a distinct divergence among immune status, TME, and chemotherapy. The external validation dataset (E-MTAB-1980) and another immunotherapy cohort (IMvigor 210) demonstrated that patients in the high IR score group had a significantly prolonged survival time and clinical benefits compared to the low IR score group. Together, characterization of molecular heterogeneity and IR signature may help develop new insights into the TME of ccRCC and provide new strategies for personalized treatment.
Catecholamine-Induced Secondary Takotsubo Syndrome in Children With Severe Enterovirus 71 Infection and Acute Heart Failure: A 20-year Experience of a Single Institute
Authors: Jan Sheng-Ling , Fu Yun-Ching , Chi Ching-Shiang , Lee Hsiu-Fen , Huang Fang-Liang , Wang Chung-Chi , Wei Hao-Ji , Lin Ming-Chih , Chen Po-Yen , Hwang Betau
Published: September 2021

Background: Acute heart failure (AHF) is the major cause of death in children with severe enterovirus 71 (EV71) infection. This study aimed to report our clinical experience with EV71-related AHF, as well as to discuss its pathogenesis and relationship to Takotsubo syndrome (TTS).

Methods: A total 27 children with EV71-related AHF between 1998 and 2018 were studied. The TTS diagnosis was based on the International Takotsubo Diagnostic Criteria.

Results: Acute heart failure-related early death occurred in 10 (37%) of the patients. Sinus tachycardia, systemic hypertension, and pulmonary edema in 100, 85, and 81% of the patients, respectively, preceded AHF. Cardiac biomarkers were significantly increased in most patients. The main echocardiographic findings included transient and reversible left ventricular (LV) regional wall motion abnormality (RWMA) with apical ballooning. High concentrations of catecholamines either preceded or coexisted with AHF. Myocardial pathology revealed no evidence of myocarditis, which was consistent with catecholamine-induced cardiotoxic damage. Patients with EV71-related AHF who had received close monitoring of their cardiac function, along with early intervention involving extracorporeal life support (ECLS), had a higher survival rate (82 vs. 30%, p = 0.013) and better neurological outcomes (59 vs. 0%, p = 0.003).

Conclusion: EV 71-related AHF was preceded by brain stem encephalitis-related hypercatecholaminemia, which resulted in a high mortality rate. Careful monitoring is merited so that any life-threatening cardiogenic shock may be appropriately treated. In view of the similarities in their clinical manifestations, natural course direction, pathological findings, and possible mechanisms, TTS and EV71-related AHF may represent the same syndrome. Therefore, we suggest that EV71-related AHF could constitute a direct causal link to catecholamine-induced secondary TTS.
NetGenes: A Database of Essential Genes Predicted Using Features From Interaction Networks
Authors: Senthamizhan Vimaladhasan , Ravindran Balaraman , Raman Karthik
Published: September 2021

Essential gene prediction models built so far are heavily reliant on sequence-based features, and the scope of network-based features has been narrow. Previous work from our group demonstrated the importance of using network-based features for predicting essential genes with high accuracy. Here, we apply our approach for the prediction of essential genes to organisms from the STRING database and host the results in a standalone website. Our database, NetGenes, contains essential gene predictions for 2,700+ bacteria predicted using features derived from STRING protein–protein functional association networks. Housing a total of over 2.1 million genes, NetGenes offers various features like essentiality scores, annotations, and feature vectors for each gene. NetGenes database is available from https://rbc-dsai-iitm.github.io/NetGenes/.
Tumor-Infiltrating B- and T-Cell Repertoire in Pancreatic Cancer Associated With Host and Tumor Features
Authors: Pineda Silvia , López de Maturana Evangelina , Yu Katharine , Ravoor Akshay , Wood Inés , Malats Núria , Sirota Marina
Published: September 2021

Background

Infiltrating B and T cells have been observed in several tumor tissues, including pancreatic ductal adenocarcinoma (PDAC). The majority known PDAC risk factors point to a chronic inflammatory process leading to different forms of immunological infiltration. Understanding pancreatic tumor infiltration may lead to improved knowledge of this devastating disease.

Methods

We extracted the immunoglobulins (IGs) and T cell receptors (TCRs) from RNA-sequencing of 144 PDAC from TCGA and 180 pancreatic normal tissue from GTEx. We used Shannon entropy to find differences in IG/TCR diversity. We performed a clonotype analysis considering the IG clone definition (same V and J segments, same CDR3 length, and 90% nucleotide identity between CDR3s) to study differences among the tumor samples. Finally, we performed an association analysis to find host and tumor factors associated with the IG/TCR.

Results

PDAC presented a richer and more diverse IG and TCR infiltration than normal pancreatic tissue. A higher IG infiltration was present in heavy smokers and females and it was associated with better overall survival. In addition, specific IG clonotypes classified samples with better prognosis explaining 24% of the prognosis phenotypic variance. On the other hand, a larger TCR infiltration was present in patients with previous history of diabetes and was associated with lower nonantigen load.

Conclusions

Our findings support PDAC subtyping according to its immune repertoire landscape with a potential impact on the understanding of the inflammatory basis of PDAC risk factors as well as the design of treatment options and prognosis monitoring.
Ubiquitin Ligases CBL and CBL-B Maintain the Homeostasis and Immune Quiescence of Dendritic Cells
Authors: Tong Haijun , Li Xin , Zhang Jinping , Gong Liying , Sun Weili , Calderon Virginie , Zhang Xiaochen , Li Yue , Gadzinski Adeline , Langdon Wallace Y. , Reizis Boris , Zou Yongrui , Gu Hua
Published: September 2021

Dendritic cells (DCs) are composed of multiple lineages of hematopoietic cells and orchestrate immune responses upon detecting the danger and inflammatory signals associated with pathogen and damaged tissues. Under steady-state, DCs are maintained at limited numbers and the functionally quiescent status. While it is known that a fine balance in the DC homeostasis and activation status is also important to prevent autoimmune diseases and hyperinflammation, mechanisms that control DC development and activation under stead-state remain not fully understood. Here we show that DC-specific ablation of CBL and CBL-B (CBL-/-CBL-B-/-) leads to spontaneous liver inflammation and fibrosis and early death of the mice. The mutant mice have a marked expansion of classic CD8α+/CD103+ DCs (cDC1s) in peripheral lymphoid organs and the liver. These DCs exhibit atypical activation phenotypes characterized by an increased production of inflammatory cytokines and chemokines but not the cell surface MHC-II and costimulatory ligands. While the mutant mice also have massive T cell activation, lymphocytes are not required for the disease development. The CBL-/-CBL-B-/- mutation enhances FLT3-mTOR signaling, due to defective FLT3 ubiquitination and degradation. Blockade of FLT3-mTOR signaling normalizes the homeostasis of cDC1s and attenuates liver inflammation. Our result thus reveals a critical role of CBLs in the maintenance of DC homeostasis and immune quiescence. This regulation could be relevant to liver inflammatory diseases and fibrosis in humans.
Case Report: Diagnostic Value of Metagenomics Next Generation Sequencing in Intracranial Infection Caused by Mucor
Authors: Liu YuChen , Zhang Jun , Han Bing , Du LiJuan , Shi ZhaoYang , Wang ChunCheng , Xu Min , Luo YongGang
Published: September 2021

mNGS(metagenomics Next Generation Sequencing), as a novel culture-independent approach, demonstrated the capability of rapid, sensitive, and accurate pathogen identification. At present, there have been many case reports about the use of mNGS to assist in the diagnosis of bacterial, fungal, viral and parasitic infections and to guide clinicians to determine appropriate treatment. However, the clinical understanding of this technique is not comprehensive, and the experience of using it is relatively limited. We reported a 53-year-old man who was admitted to hospital with a high fever and headache. His inflammatory biomarkers were markedly elevated. Based on the clinical presentation, He was initially diagnosed as having an intracranial infection of unknown etiology and received empirical antibiotics and systemic supportive treatment. But these did not relieve his symptoms. Both the blood and CSF specimens were examined using traditional culture, serological testing, and mNGS. Traditional culture and serological testing produced negative results, while the mNGS revealed the presence of a potential pathogen, mucor, in the CSF specimen. Then targeted antifungal treatment was selected quickly and his temperature gradually returned to normal. Thus, we report the case in which mNGS was an auxiliary method to diagnose mucormycosis, and discuss this case in combination with relevant literature, in order to improve the clinical cognition of this technology.
Risk Factors for High-Risk Adenoma on the First Lifetime Colonoscopy Using Decision Tree Method: A Cross-Sectional Study in 6,047 Asymptomatic Koreans
Authors: Chung Kwang Hyun , Park Min Jung , Jin Eun Hyo , Seo Ji Yeon , Song Ji Hyun , Yang Sun Young , Kim Young Sun , Yim Jeong Yoon , Lim Seon Hee , Kim Joo Sung , Chung Su Jin , Park Joo Kyung
Published: September 2021

Background/Aims: As risk of colorectal neoplasm is varied even in persons with “average-risk,” risk evaluation and tailored screening are needed. This study aimed to evaluate the risk factors of high-risk adenoma (HRA) in healthy individuals and determine the characteristics of advanced neoplasia (AN) among individual polyps.

Methods: Asymptomatic adults who underwent the first lifetime screening colonoscopy at the Seoul National University Hospital Healthcare System Gangnam Center (SNUH GC) were recruited from 2004 to 2007 as SNUH GC Cohort and were followed for 10 years. Demographic and clinical characteristics were compared between the subjects with and without AN (≥10 mm in size, villous component, and/or high-grade dysplasia and/or cancer) or HRA (AN and/or 3 or more adenomas). For individual polyps, correlations between clinical or endoscopic features and histologic grades were evaluated using a decision tree method.

Results: A total of 6,047 subjects were included and 5,621 polyps were found in 2,604 (43%) subjects. Advanced age, male sex, and current smoking status were statistically significant with regards to AN and HRA. A lower incidence of AN was observed in subjects taking aspirin. In the decision tree model, the location, shape, and size of the polyp, and sex of the subject were key predictors of the pathologic type. A weak but significant association was observed between the prediction of the final tree and the histological grouping (Kendall's tau-c = 0.142, p < 0001).

Conclusions: Advanced neoplasia and HRA can be predicted using several individual characteristics and decision tree models.