bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional characterization of reappearing B cells after anti-CD20 treatment of CNS autoimmune disease
Authors: Häusler Darius , Häusser-Kinzel Silke , Feldmann Linda , Torke Sebastian , Lepennetier Gildas , Bernard Claude C. A. , Zamvil Scott S. , Brück Wolfgang , Lehmann-Horn Klaus , Weber Martin S.
Published: September 2018

Significance

B cell depletion via anti-CD20 monoclonal antibodies is a novel, highly efficient therapy for multiple sclerosis (MS). In a murine MS model, we investigated three mechanistic questions that cannot be addressed in humans. First, we established that a fraction of mature B cells in the spleen is resistant to anti-CD20. Second, we determined that, after cessation of treatment, splenic and bone-marrow B cells reconstitute in parallel, substantially preceding B cell reappearance in blood. Third, we observed that, in a model involving activated B cells, the post–anti-CD20 B cell pool contained an elevated frequency of differentiated, myelin-reactive B cells. Together, our findings reveal mechanisms by which pathogenic B cells may persist in anti-CD20 treatment.
Endothelial cell fitness dictates the source of regenerating liver vasculature
Authors: Singhal Mahak , Liu Xiaoting , Inverso Donato , Jiang Kai , Dai Jianing , He Hao , Bartels Susanne , Li Weiping , Abdul Pari Ashik Ahmed , Gengenbacher Nicolas , Besemfelder Eva , Hui Lijian , Augustin Hellmut G. , Hu Junhao
Published: September 2018

Neoangiogenesis plays a key role in diverse pathophysiological conditions, including liver regeneration. Yet, the source of new endothelial cells (ECs) remains elusive. By analyzing the regeneration of the liver vasculature in irradiation-based myeloablative and nonmyeloablative bone marrow transplantation mouse models, we discovered that neoangiogenesis in livers with intact endothelium was solely mediated by proliferation of resident ECs. However, following irradiation-induced EC damage, bone marrow–derived mononuclear cells were recruited and incorporated into the vasculature. Further experiments with direct bone marrow infusion or granulocyte colony–stimulating factor (G-CSF)–mediated progenitor cell mobilization, which resembles clinically relevant stem cell therapy, demonstrated that bone marrow–derived cells did not contribute to the regeneration of liver vasculature after two-thirds partial hepatectomy (PHx). Taken together, the data reconcile many of the discrepancies in the literature and highlight that the cellular source of regenerating endothelium depends on the fitness of the residual vasculature.
Piezo1 and Gq/G11 promote endothelial inflammation depending on flow pattern and integrin activation
Authors: Albarrán-Juárez Julián , Iring Andras , Wang ShengPeng , Joseph Sayali , Grimm Myriam , Strilic Boris , Wettschureck Nina , Althoff Till F. , Offermanns Stefan
Published: September 2018

The vascular endothelium is constantly exposed to mechanical forces, including fluid shear stress exerted by the flowing blood. Endothelial cells can sense different flow patterns and convert the mechanical signal of laminar flow into atheroprotective signals, including eNOS activation, whereas disturbed flow in atheroprone areas induces inflammatory signaling, including NF-κB activation. How endothelial cells distinguish different flow patterns is poorly understood. Here we show that both laminar and disturbed flow activate the same initial pathway involving the mechanosensitive cation channel Piezo1, the purinergic P2Y2 receptor, and Gq/G11-mediated signaling. However, only disturbed flow leads to Piezo1- and Gq/G11-mediated integrin activation resulting in focal adhesion kinase-dependent NF-κB activation. Mice with induced endothelium-specific deficiency of Piezo1 or Gαq/Gα11 show reduced integrin activation, inflammatory signaling, and progression of atherosclerosis in atheroprone areas. Our data identify critical steps in endothelial mechanotransduction, which distinguish flow pattern-dependent activation of atheroprotective and atherogenic endothelial signaling and suggest novel therapeutic strategies to treat inflammatory vascular disorders such as atherosclerosis.
Activated PIK3CD drives innate B cell expansion yet limits B cell–intrinsic immune responses
Authors: Wray-Dutra Michelle N. , Al Qureshah Fahd , Metzler Genita , Oukka Mohamed , James Richard G. , Rawlings David J.
Published: September 2018

Activated PI3K-delta syndrome (APDS) is an immunodeficiency caused by gain-of-function mutations in PIK3CD. This disease exhibits complex immune phenotypes including increased IgM, recurrent infection, and impaired vaccine responses. To better understand the impact of B cells in this disease, we generated an inducible model of the common APDS mutation (hPIK3CD-E1021K; referred to as aPIK3CD) and intercrossed these mice with B cell–specific Cre models. Mb1-aPIK3CD mice exhibited bone marrow B lymphopenia and, conversely, expansion of the peripheral innate B1a and MZ B cell compartments. aPIK3CD B cells manifest increased pS6 and increased survival at several stages, without alterations in cycling, and baseline increases in plasma cells, natural IgM, and IgG3. Finally, Mb1-aPIK3CD mice exhibited blunted T cell–independent immune responses, and both AID- and CD21-aPIK3CD mice displayed reduced class-switched antibodies following T cell–dependent immunization. Thus, aPIK3CD alters B cell development and function and is counter-productive during immune responses, providing insight into B cell–intrinsic contributions to the APDS phenotype.
Generic 2-parameter perturbations of parabolic singular points of vector fields in ℂ
Authors: Klimeš Martin , Rousseau Christiane
Published: September 2018

We describe the equivalence classes of germs of generic

2
2

-parameter families of complex vector fields

z
˙

=

ω
ϵ

(
z
)

\dot z = \omega _\epsilon (z)

on

C

\mathbb {C}

unfolding a singular parabolic point of multiplicity

k
+
1

k+1

:

ω
0

=

z

k
+
1

+
o
(

z

k
+
1

)

\omega _0= z^{k+1} +o(z^{k+1})

. The equivalence is under conjugacy by holomorphic change of coordinate and parameter. As a preparatory step, we present the bifurcation diagram of the family of vector fields

z
˙

=

z

k
+
1

+

ϵ
1

z
+

ϵ
0

\dot z = z^{k+1}+\epsilon _1z+\epsilon _0

over

C

P

1

\mathbb {C}\mathbb {P}^1

. This presentation is done using the new tools of periodgon and star domain. We then provide a description of the modulus space and (almost) unique normal forms for the equivalence classes of germs.
Reproduction, Birth Control, and Motherhood in the United States
Authors: Solinger Rickie
Published: September 2018

The history of reproductive politics in the United States incorporates several centuries of struggle and resistance and virtually no periods of quiescence. The state and other institutions have frequently clashed within and against each other and with girls and women, over who has primary power to govern female sexuality, fertility, and maternity: institutions, or women themselves. These struggles have always been racialized. From the eighteenth century forward, authorities have promulgated laws and public policies embedding population-control aims, investing some groups with greater reproductive value than others. In the modern era, “choice” emerged as the mark of reproductive freedom, chiefly defined as the right to limit and terminate pregnancy. More recently, “reproductive justice” contends that all people have the human right to be a parent; to forgo parenting; and to access the resources required to exercise the first two rights with dignity and safety.
Women, the Civil War, and Reconstruction
Authors: Rosen Hannah
Published: September 2018

The rapid transformations brought on by the US Civil War and its aftermath touched women’s lives in contradictory ways. The disruption caused by war and the destruction of slavery opened up space, and at times created the necessity, for radically new roles for women that challenged antebellum gender norms and racial and class hierarchies. This essay examines the wartime and postwar experiences primarily of black and white but also Native American women. In this period, many women faced new circumstances that inspired them to confront power in novel ways—by, for instance, fleeing slavery, petitioning governors, organizing bread riots, participating in political parades, or protesting segregation. The chapter also explores political violence in the postwar period that affected women differently across class, race, and region and that eventually helped to shut down the radical potential of the era.
Women at Play in Popular Culture
Authors: Kibler M. Alison
Published: September 2018

The story of women’s participation in popular culture is more complex than the struggle to be included. Feminist activists have fought for legislation to end discrimination in leisure, sports, and popular culture. At the same time, advertisers have coopted feminism to sell a variety of products as symbols of emancipation for women, substituting purchasing power for political power. Gaining visibility in the media and as target audiences, and breaking into male spheres have not been the end of these feminist struggles; rather, women who gained opportunities in sport and leisure were often stereotyped as “mannish” or cast in reassuring feminine roles—beauty icons or heterosexual romantic heroines. It is important to trace women’s pathbreaking roles as spectators, fans, performers, and athletes as well as show how sport and popular culture are fundamentally gendered.
Women and World War in Comparative Perspective
Authors: Winchell Meghan K.
Published: September 2018

This chapter compares women’s experiences in World War I and World War II, emphasizing the ways that wartime mobilization shaped the citizenship claims, cultural representations, labor experiences, military contributions, and sexual expression of diverse groups of women. It focuses on how women applied their gendered, racialized, and classed bodies to wartime experiences that often put them at odds with propaganda images of femininity. The wartime context inspired the actions of women like gold star mothers who represented sacrifice, activists who fought for women suffrage, and African Americans who protested segregation. Some women embodied Rosie the Riveter by working in war industries, many cultivated victory gardens, and others served in the Women’s Army Corps. Young women found themselves caught in government projects to curtail venereal disease while seeking sexual autonomy.
Transgender Representations, Identities, and Communities
Authors: Manion Jen
Published: September 2018

Accounts of people who crossed genders, either temporarily or for a lifetime, are well known to historians. The emerging field of transgender studies has raised a new set of questions for scholars intent on unpacking more fully the meaning of the lives of people who were never neatly contained by the categories of “man” or “woman.” A historic approach to this subject is invaluable since particular historic periods signaled significant changes in how such people were perceived and treated by institutions, including the state and the medical establishment. Another crucial axis of difference exists between dominant understandings of those who were assigned the female sex at birth and those who were assigned the male sex at birth.
Introduction
Authors: Sedighi Anousha , Shabani-Jadidi Pouneh
Published: September 2018

This chapter offers an introduction to the volume by providing a brief description of its thematic sections (Classification and History, The Sound System, Syntax, Language and Words, Language and People, and Language, Mind, and Technology) and their related chapters. These thematic sections cover both the theoretical and the applied aspects of the Persian language and provide a comprehensive overview of the field of Persian linguistics by discussing its development, capturing critical accounts of cutting edge research, as well as outlining current debates and suggesting productive lines of future research. The chapter also discusses the goals and ambitions of the editors in putting such volume together. It also points out the logic behind the selection of the contributors and addresses the challenges the editors endured throughout the project.
Lexicography
Authors: Assi Seyed Mostafa
Published: September 2018

The history of lexicography in Iran dates back to more than 2,000 years ago, to the time of the compilation of bilingual and monolingual lexicons for the Middle Persian language. After a review of the long and rich tradition of Persian lexicography, the chapter gives an account of the state of the art in the modern era by describing recent advances and developments in this field. During the last three or four decades, in line with the advancements in western countries, Iranian lexicography evolved from its traditional state into a modern professional and academic activity trying to improve the form and content of dictionaries by implementing the following factors: the latest achievements in theoretical and applied linguistics related to lexicography; and the computer techniques and information technology and corpus-based approach to lexicography.
Computational Linguistics
Authors: Megerdoomian Karine
Published: September 2018

This chapter introduces the fields of Computational Linguistics (CL)—the computational modelling of linguistic representations and theories—and Natural Language Processing (NLP)—the design and implementation of tools for automated language understanding and production—and discusses some of the existing tensions between the formal approach to linguistics and the current state of the research and development in CL and NLP. The paper goes on to explain the specific challenges faced by CL and NLP for Persian, much of it derived from the intricacies presented by the Perso-Arabic script in automatically identifying word and phrase boundaries in text, as well as difficulties in automatic processing of compound words and light verb constructions. The chapter then provides an overview of the state of the art in current and recent CL and NLP for Persian. It concludes with areas for improvement and suggestions for future directions.
Other Approaches to Syntax
Authors: Ghomeshi Jila
Published: September 2018

This chapter surveys theoretical approaches to Persian syntax, with an emphasis on more recent work. It begins with a brief discussion of what constitutes a theoretical, as opposed to descriptive, approach, and proceeds with a look at Linguistic Typology, Construction Grammar, and Cognitive, Functionalist, and Corpus approaches. At the end of the chapter, formal approaches such as RRG, HPSG, and LFG are touched upon as well as formal generative work prior to Minimalism, which is covered in the previous chapter. The discussion in each case is intended to showcase the way in which aspects of Persian syntax have been addressed. The advantages to considering Persian both in a historical context and within the family of other Iranian languages is highlighted, and a number of distinctive constructions within the language are discussed in light of how they have been treated within the literature.
The Text of The Gospel and Letters of John
Authors: Houghton Hugh A. G.
Published: September 2018

The textual transmission of the Gospel and Letters of John provides evidence both for their earliest text and its reception across the centuries. This chapter first considers the sources for these writings, comprising Greek papyrus, majuscule, and minuscule manuscripts, early translations into Latin, Coptic, and Syriac, and quotations in Christian writers. The form, contents, and distribution of the documents sheds light on their understanding and use: the Johannine writings were rarely transmitted together; they were particularly popular in Egypt; gospel manuscripts were used as amulets and for divination. Following an introduction to currently scholarly editions, notably the Editio Critica Maior, a selection of readings is presented to exemplify the nature of textual variants in these writings and how they are evaluated. This includes passages which were not originally present, including the Woman Taken in Adultery and the Johannine Comma.
Social-Scientific Readings of the Gospel and Letters of John
Authors: Esler Philip F.
Published: September 2018

This chapter surveys the development of social-scientific readings of the Johannine Gospel and Letters in roughly chronological order from the introduction of the sociology of knowledge and sectarianism to Johannine scholarship by Wayne Meeks in 1972, and the application of sectarian perspectives, especially influenced by Bryan Wilson’s typology of sectarianism, in the 1980s and 1990s. Sociolinguistic insights into anti-society and anti-language to understand the Johannine Sondersprache were also introduced in the 1980s together with Mary Douglas’ notions of grid and group and notions of Mediterranean culture. Applications of sectarianism and Mediterranean culture continued into the 2000s, but were accompnaied by new interests in identity, including the tension between Judean ethnic and Christ-movement identities in the Fourth Gospel, and in collective memory studies. All of these approaches continue to have a role in understanding the Johannine corpus.
The Person of Jesus Christ in the Gospel of John
Authors: Schnelle Udo
Published: September 2018

In the Gospel of John, the narrative is determined and driven by two issues: (1) the nature of the person of Jesus Christ and (2) the conflict between faith and unbelief. The Prologue at the start already gives basic answers to these questions. In the first part of the Gospel (John 1:19–12: 50), the miracle stories shape the narrative and theological centre: in the signs, Jesus turns to humanity. In the second part (John 13:1–20: 31), the teaching and suffering of Jesus Christ dominate. The Christological titles are embedded in the whole narrative. Narrative Christology and titular Christology are linked in John, but at the same time, the Christological titles have their own significance because, as storehouses of knowledge and bearers of meaning, they express concisely who and what Jesus Christ is for believers. Finally, theological concerns determine the structure of the Fourth Gospel.
Temple, Festivals, and Scripture in the Gospel Of John
Authors: Schuchard Bruce G.
Published: September 2018

The recent study of the Gospel and Epistles of John has aptly noted the extent to which Israel’s Scriptures consistently inform the foundation upon which especially the Gospel was written. So pervasive is Scripture’s influence on the Gospel that its narrated sequence of events is wedded to a series of Jewish festivals founded upon Scripture whose focus is the centre of Israel’s faith and life that was the city of Jerusalem and its Temple. Therefore, the Gospel’s thoroughgoing interest in Temple, festivals, and Scripture has fittingly attracted the attention of a steadily increasing number of scholars, whose work has shed important light on the literary and theological nature of both the Gospel and the Epistles. This chapter offers a brief description of some of the most important recent research that showcases latest developments in the study of Temple, festivals, and Scripture in the Gospel and Epistles of John.
The Johannine Literature in a Greek Context
Authors: Buch-Hansen Gitte
Published: September 2018

This chapter focuses on the scholarly debate in the twentieth century about the relationship between John’s Gospel and Greek philosophy. Initially, attention is drawn to the link, which characterizes the discussion in the first part of the century, between the dating of the Fourth Gospel and its ideological worldview. Next, it turns toward the alleged inspiration from Jewish Wisdom traditions in the composition of the Prologue and demonstrates how scholars’ references to Wisdom have served the most diverse—and even opposing—purposes: to ward off philosophical speculation, to replace Jewish mythology and apocalypticism by Greek rationality, to illustrate the Prologue’s Middle Platonism, and to introduce Stoicism into John’s thinking. Finally, it demonstrates how readings of the Prologue in light of Aristotle’s theory of epigenesis have displaced the focus from the logos to the pneuma and thereby managed to extend the discussion about influence from Greek philosophy beyond the Prologue.
The Relationship Between Syntactic Production and Comprehension
Authors: Indefrey Peter
Published: September 2018

This chapter deals with the question of whether there is one syntactic system that is shared by language production and comprehension or whether there are two separate systems. It first discusses arguments in favor of one or the other option and then presents the current evidence on the brain structures involved in sentence processing. The results of meta-analyses of numerous neuroimaging studies suggest that there is one system consisting of functionally distinct cortical regions: the dorsal part of Broca’s area subserving compositional syntactic processing; the ventral part of Broca’s area subserving compositional semantic processing; and the left posterior temporal cortex (Wernicke’s area) subserving the retrieval of lexical syntactic and semantic information. Sentence production, the comprehension of simple and complex sentences, and the parsing of sentences containing grammatical violations differ with respect to the recruitment of these functional components.
Socially Connecting Through Blogs and Vlogs
Authors: Okdie Bradley M. , Rempala Daniel M.
Published: September 2018

People need to create and maintain social connections, and the ways these connections are made and maintained have broadened with the advent of the Internet. One way that people may attempt to satisfy their need to belong is through online self-expression such as blogging. This chapter examines blogging and its derivations (e.g., microblogging, vlogging) and analyzes current trends and motivations using a social connections lens. The chapter explicates the motivations for blogging using recent literature and extends these findings to include more recently developed, blog-like Internet platforms. Finally, the chapter closes with a discussion of the future of blogging motivations.
Video Games and Behavior Change
Authors: McCain Jessica , Morrison Kyle , Ahn Sun Joo
Published: September 2018

This chapter explores how video games interact with individual characteristics to afford unique opportunities for behavior change. It first considers how video games differ from traditional media, and more specifically how they create virtual situations that may be perceived differently from those naturally occurring in reality. In this regard, the concept of situational affordance is discussed. It then examines simulated experiences provided by video games before describing a range of psychosocial pathways (both cognitive and affective) through which video games can impact behavior change both intentionally and inadvertently (motivation, personalization, Proteus Effect). It also recommends game elements aimed at eliciting behavior change and highlights some concrete applications that illustrate how games or game elements can be used to induce and sustain changes in health attitudes and behaviors. Finally, it identifies several areas for future research that are emerging in the field of game studies.
Propositions and Truth-Bearers
Authors: King Jeffrey C.
Published: September 2018

The chapter begins by reviewing the roles that advocates of propositions take them to play. Then it turns to the question of the nature of the things that play these roles. What is the correct metaphysics of propositions? Since most contemporary thought about the nature of propositions is traceable in some way to the classical theories of propositions of Gottlob Frege and Bertrand Russell, those theories are discussed in some detail. Then accounts of the metaphysics of propositions developed in 1960s are discussed. The chapter concludes by reviewing other accounts of propositions developed between the 1960s and the present.
Truth in Fictionalism
Authors: Burgess Alexis
Published: September 2018

What does realism about an arbitrary subject-matter have to do with truth? Some views say everything, others hardly anything. Both answers are reflected in ongoing debates between self-styled realists and anti-realists in metaphysics, and other areas. Error theory, nonfactualism, fictionalism, and other forms of opposition to realism are normally articulated and differentiated using the notions of truth and falsity. Given its preoccupation with the limits of literal representation, fictionalism can seem especially ensared in semantics and/or the theory of mental content. Be that as it may, the present chapter aims to establish that there remains an important sense in which the fictionalist gambit does not essentially have anything to do with truth or falsity. In particular, many recognizably fictionalist positions are compatible with nominalism about truths: the view that nothing whatsoever is true.
Tarski on the Concept of Truth
Authors: Ray Greg
Published: September 2018

Alfred Tarski’s work on truth has been so central to the discourse on truth that most coming to it for the first time have probably already heard a great deal about what is said there. Unfortunately, since the work is largely technical and Tarski was only tangentially philosophical, a certain incautious assimilation dominates many philosophical discussions of Tarski’s ideas, and so, examining Tarski on the concept of truth is in many ways an act of unlearning. This chapter will focus on key ideas in Tarski’s work that have had a lasting impact: T-sentence, Convention T, Tarskian truth definition, and Tarski’s general limiting theses on the expressibility and definability of truth. Though these ideas are familiar in name, the chapter seeks to uncover and remove certain widespread misunderstandings. Tarski’s name also features prominently in discussions of the liar paradox, so we will discuss Tarski’s misunderstood connection to this ancient puzzle.
Non-Classical Theories of Truth
Authors: Beall Jc , Ripley David
Published: September 2018

This chapter gives a brief overview of theories of truth based on non-classical logics. It sticks to the most central motivation for such theories—the liar paradox—and focuses on a range of responses that have been made to this paradox. The chapter presents the paradox, and shows how it leads to trouble for classical logic. Then the chapter proceeds to lay out four families of response, which we call “paracomplete,” “paraconsistent,” “nontransitive,” and “noncontractive.” For each kind of theory, the chapter goes on to show how it can block paradoxical derivations, and gives references to sources that develop it more fully.
Idealism and the Question of Truth
Authors: Tolley Clinton
Published: September 2018

This chapter traces developments in idealist theories of truth in and after Kant, focusing especially on key moments in the nineteenth-century history of analytic philosophy and phenomenology. Though Kant intended his transcendental idealism to effect a Copernican revolution in philosophy, he did not advocate for revisions in the traditional definition of truth in terms of a correspondence or agreement between our judgments and their objects. Many of his successors countered that it was only by carefully revisiting the nature of truth itself that philosophy could hope to avoid the “subjectivizing” pitfalls they saw latent in Kantian idealism. Intense post-Kantian reflection on the concept of truth led to a series of accounts which were deeply influential across a number of philosophical traditions and which provide the crucial proximate historical and conceptual context for many of the most influential discussions of truth, and semantics more generally, in the twentieth century.
The Coherence Theory of Truth
Authors: Walker Ralph
Published: September 2018

The coherence theory holds that truth consists in coherence amongst our beliefs. It can thus rule out radical scepticism and avoid the problems of the correspondence theory. Considerations about meaning and verification have also pointed philosophers in the same direction. But if it holds all truth to consist in coherence it is untenable: there must be some truths that do not, truths about what people believe. This causes problems for traditional coherence theories, and also for verificationists and anti-realists. The admission of a grounding class of truths that do not consist in coherence also raises the question why there should be such systematic agreement between these. This cannot properly be explained by anything that is said within the theory whose truth is constituted by coherence with the grounding class. Kant saw this problem, and postulated “things as they are in themselves.” Others dismiss it; but that is not satisfactory.
Hemofiltration Successfully Eliminates Severe Cytokine Release Syndrome Following CD19 CAR-T-Cell Therapy
Authors: Liu Yanfen , Chen Xinfeng , Wang Dao , Li Hong , Huang Jianmin , Zhang Zhen , Qiao Yingjin , Zhang Hongling , Zeng Ying , Tang Chao , Yang Shuangning , Wan Xiaochun , Chen Youhai H. , Zhang Yi
Published: September 2018

Cytokine release syndrome (CRS) remains to be a major adverse effect of chimeric antigen receptor T (CAR-T) cell therapy in B-cell acute lymphoblastic leukemia (B-ALL) and lymphoma. It was urgent to explore novel strategy for managing severe CRS. We conducted a clinical trial to assess the safety and efficacy of CD19-targeting CAR-T-cells in the treatment of relapsed and chemotherapy-refractory B-ALL and lymphoma. A 10-year-old boy with B-ALL who never achieved minimal residual disease (MRD) negative status after 5 courses of chemotherapy was enrolled into our study and received a total of 3.19×106/kg autologous CD19 CAR-T-cells. Before CAR-T-cell infusion, naive lymphocytes made up 41.8% of bone marrow cells, which were reduced to 1% at the 14th day after transfusion, with MRD<10−4. However, this patient developed grade 4 CRS, multiple organ failure, hemophagocytic syndrome, neurotoxicity, and severe pulmonary infection after CAR-T-cell therapy. Tocilizumab and glucocorticoids treatment were ineffective for controlling the adverse effects and in contrast, hemofiltration immediately ameliorated the severe CRS and prevented the exacerbation of multiple organ dysfunction, pneumonia, and hydrosarca caused by CAR-T-cell therapy. All side effects disappeared within days following hemofiltration. Hemofiltration helped quickly clear cytokines, speeded up patient recover, and successfully resolved the severe CRS crisis. This was the first report, reporting the successful use of hemofiltration to eliminate adverse reactions of CAR-T-cell therapy.
Assessing Religious Commitment and Satisfaction
Authors: Cyphers Natalie A. , Clements Andrea D.
Published: September 2018

Survey instruments have been developed to measure whether someone claims to be religious but do not address the degree to which someone is satisfied with their religious commitment. The Religious Surrender and Attendance Satisfaction Scale (RSASS) was revised to measure both a person's level of religious commitment and satisfaction with level of religious commitment. This study was conducted to determine initial validity for the satisfaction portion of the RSASS. Construct validity measures provided initial confirmation of the utility of RSASS as a measure of satisfaction with religious commitment, that can be used by nurses in practice and research.
Serving on a Board of Nursing
Authors: DeKoninck Beth
Published: September 2018

What is it like to serve on a State Board of Nursing (BON)? How does one deal with the weight of the responsibility, the discomfort of inexperience in the role, and integrate personal faith with the professional expectations of administering justice and discipline? The author defines the patients cared for in the BON role and the balance of discipline with care for nurses.
Functional and Aesthetic Factors Associated with Revision of Rhinoplasty
Authors: Bouaoud Jebrane , Loustau Marine , Belloc Jean-Baptiste
Published: September 2018

Background:

Surgical revision rate of rhinoplasty is from 5% to 15% in literature. The aims of our study were to define the rate and the predictive factors for surgical revision of rhinoplasty.

Methods:

We have realized a single-center case/control study including 62 patients who underwent surgical revision among 732 patients who underwent closed rhinoplasty between 2005 and 2015. Data of each rhinoplasty were collected from medical records and photographs. Statistical analyses were used.

Results:

The surgical revision rate was 8.6%. After multivariate analysis, 4 factors were statistically significant and independently associated with surgical revision: “preexisting respiratory functional disorder” [odds ratio OR = 3.30; 95% CI (1.47–7.76);P= 0.004], “wide nasal bone and side walls” [OR = 3.94; 95% CI (1.49–11.25);P= 0.007], “deviated nasal bone and side walls” [OR = 2.68; 95% CI [1.14–6.58];P= 0.02] and the use of camouflage grafts [OR = 0.26; 95% CI [0.07–0.89];P= 0.04].

Conclusions:

Closed rhinoplasties have similar revision rate to open techniques. Revision surgeries are justified by functional or aesthetic disorders. The interests of this study are to better inform patients and to adapt operative management. We provide here some recommendations with focus on the keys to successful rhinoplasty surgery.
Cutaneous Breast Radiation-associated Angiosarcoma: Anterior Chest Wall Reconstruction Options Following Extra-radical Resection
Authors: Mella Juan R. , Ross Kimberly M. , Li George Z. , Pomahac Bohdan , Raut Chandrajit P. , Orgill Dennis P.
Published: September 2018

Background:

Radiation-associated angiosarcoma (RAAS) of the breast is a rare complication following breast irradiation with high rates of recurrence and death. To improve survival, we have advocated for an extra-radical resection where the entire irradiated skin and subcutaneous tissue is excised. This results in very large chest defects for which we describe our reconstructive experience.

Methods:

We performed a retrospective review of patients diagnosed with RAAS and treated with extra-radical resection followed by immediate reconstruction between 1999 and 2017. We analyzed reconstructive options, complications rates, length of stay, and operative times.

Results:

Extra-radical resections were performed in 35 patients. We reconstructed these large defects with abdominal advancement flaps with split-thickness skin grafting in 25 patients and added a pedicled latissimus dorsi or omental flap in the 10 other patients. Skin grafts took well over the irradiated pectoralis major muscle with a median take rate of over 90%. Average operative times were 150 minutes for those treated with an abdominal advancement flap and skin grafting with a median length of stay of 5 days for all patients.

Conclusion:

Large anterior chest soft-tissue defects caused by extra-radical resections leaves defects too large to be covered by traditional breast reconstruction flaps. Abdominal advancement, latissimus dorsi muscle, and omental flaps along with skin grafts can be safely performed while leaving other traditional options open for future breast reconstruction.
Early Experience With Nonporous Polyethylene Barrier Sheet in Orbital Fracture Repair
Authors: Compton Christopher J. , Melson Andrew T. , Sokol Jason A. , Nunery William R. , Ochoa Manuel , Ziaie Babak , Lee H.B. Harold
Published: September 2018

Purpose:

The aim of this study was to evaluate the efficacy of the nonporous polyethylene barrier sheet as an alternative for nylon foil (SupraFOIL) implants in repair of orbital fractures.

Methods:

This is a prospective, case series using the Stryker 0.4-mm-thick nonporous polyethylene barrier sheet in all patients over the age of 18 years presenting with orbital fractures from December 2014 to June 2015. Patient’s age, location of fracture, etiology of injury, presence of preoperative restriction and diplopia, and postoperative diplopia and/or enophthalmos was recorded. Institutional review board approval was received, and consent was obtained from all participants. Patients were followed for at least 6 months when possible. Scanning electron microscopy was used to compare the thickness, surface characteristics, and porosity of the nonporous polyethylene barrier and nylon foil implants. Beam deflection testing was also performed to compare the biomechanical properties of each implant.

Results:

Forty-six patients who underwent repair of orbital fractures with the nonporous polyethylene barrier sheet were included in this series. Average age was 43.3 years (range: 18–84 years). Twenty-six of 46 patients (56.5%) were males, and 20 (43.4%) were females. The most common causes of injuries were assault (38.3%), falls (25.5%), motor vehicle accident (14.9%), and sports related (10.5%). Twenty of 46 patients (43.4%) had isolated orbital floor, and 2 patients (4.3%) had isolated medial wall fractures. Fifteen patients (32.6%) had combined floor and medial wall fractures involving the inferomedial orbital strut, and 9 (19.6%) had floor fractures associated with zygomaticomaxillary complex or lateral wall fractures. Twenty-eight patients (60.9%) had preoperative diplopia. Timing of surgery was between 3 and 55 days, with the median of 11.5 days. Five of 46 patients (10.8%) had residual diplopia at their 1-week postoperative visit, 4 of those patients’ diplopia had resolved at 2 months postoperatively. One patient had residual diplopia at 6-month follow up. Electron microscopy showed that the 0.4-mm nonporous polyethylene barrier implant was thinner (0.33 mm) than expected and thinner than 0.4-mm SupraFOIL (0.38 mm). Scanning electron microscopy exhibited that the surface of the nonporous polyethylene barrier was smooth and nonporous. Beam deflection testing showed that for small forces (<100 mN), the 2 materials behaved nearly identically, but at higher forces, the nonporous polyethylene implant exhibited less stiffness.

Conclusions:

The use of nonporous polyethylene barrier sheet implant for orbital fracture repair is a safe and effective alternative to nonporous nylon foil implants. There were no complications and one case of residual diplopia (2.1%) in this case series.
Necrotizing Orbital Cellulitis Secondary to Odontogenic Streptococcus constellatus
Authors: Li Emily , Distefano Alberto , Sohrab Mahsa
Published: September 2018

A 69-year-old woman with orbital cellulitis secondary to odontogenic Streptococcus constellatus was transferred to the authors’ institution for surgical management of infection refractory to intravenous antibiotics. She underwent debridement with preservation of the globe, recovering full motility. Visual recovery was limited by optic nerve ischemia. This case supports the importance of urgent surgical drainage in necrotizing orbital infections secondary to odontogenic Streptococcus constellatus.
Mealtime Assistance ... From Chaos to Calm
Authors: Sykes Pamela , Norris Ian , Cook Megan , Woods Aaron , Boughton Rachel , Chilcott Kylie , Walsh Kenneth
Published: September 2018

Background:

Providing appropriate and timely mealtime assistance to hospitalized patients should be part of a multifaceted and multidisciplinary approach to optimizing a patient's nutritional care plan.

Problem:

There was anecdotal evidence at the study hospital that patients did not receive adequate and/or timely assistance at mealtimes.

Approach:

A best practice implementation project, using a proven strategy of audit, feedback, and reaudit, was used to effect practice change on an acute general medical ward.

Outcomes:

The combined interventions of staff engagement, redesigning the model of care to reprioritize activities at mealtimes, clarifying nutritional care roles and responsibilities, introducing a protected mealtime and a novel 2-tiered colored tray system, and implementing an awareness and education program have resulted in significant improvements in mealtime assistance.

Conclusions:

Success of the project is considered to be replicable and sustainable hospitalwide and more broadly.
Using Lean Six Sigma to Improve Controlled Drug Processes and Release Nursing Time
Authors: Creed Maria , McGuirk Michelle , Buckley Ruth , De Brún Aoife , Kilduff Marie
Published: September 2018

Background:

Hospital controlled drug processes are established to adhere to legislation, with little consideration of efficiency of processes.

Local Problem:

A controlled drug process existed, where nurses requested a porter to collect a hand-written order; however, only 19% of drug orders were processed this way. Instead, an unscheduled, ad hoc process led to an average of 17 nurse journeys to pharmacy daily. We aimed to reduce nurse journeys to the pharmacy by 25% to release nursing time.

Methods:

A pre-/postintervention design was used with Lean Six Sigma methods.

Interventions:

A multifaceted intervention involved process redesign, increasing the frequency of a porter-led delivery service, amending delivery times to reflect times of greatest need, and streamlining checking requirements.

Results:

Following implementation, there was a statistically significant 44% decrease in nurse journeys to pharmacy for drug collections, which was maintained after 18 months.

Conclusions:

Interprofessional collaboration improving hospital-wide processes can have significant benefits for the release of nursing time.
Unjamming overcomes kinetic and proliferation arrest in terminally differentiated cells and promotes collective motility of carcinoma
Authors: Palamidessi Andrea , Malinverno Chiara , Frittoli Emanuela , Corallino Salvatore , Barbieri Elisa , Sigismund Sara , Di Fiore Pier Paolo , Beznoussenko Galina V. , Martini Emanuele , Garre Massimiliano , Parazzoli Dario , Ferrara Ines , Tripodo Claudio , Giavazzi Fabio , Cerbino Roberto , Scita Giorgio
Published: September 2018

During wound repair, branching morphogenesis and carcinoma dissemination, cellular rearrangements are fostered by a solid-to-liquid transition known as unjamming. The biomolecular machinery behind unjamming, its physiological and clinical relevance remain, however, a mystery. Here, we combine biophysical and biochemical analysis to study unjamming in a variety of epithelial 2D and 3D collectives: monolayers, differentiated normal mammary cysts, spheroid models of breast ductal carcinoma in situ (DCIS), andex vivoslices of orthotopically-implanted DCIS. In all cases, elevation of the small GTPase RAB5A sparks unjamming by promoting non-clathrin-dependent internalization of epidermal growth factor receptor that leads to hyper-activation of endosomally-confined ERK1/2 and phosphorylation of the actin nucleator WAVE2. Physically, activation of this pathway causes highly coordinated flocking of the cells, with striking rotational motion in 3D that eventually leads to matrix remodelling and collective invasiveness of otherwise jammed carcinoma. The identified endo-ERK1/2 pathway provides an effective switch for unjamming through flocking to promote epithelial tissues morphogenesis and carcinoma invasion and dissemination.
Repression of Transcription Factor AP-2 Alpha by Peroxisome Proliferator Activated Receptor Gamma Reveals a Novel Transcriptional Circuit in basal-squamous Bladder Cancer
Authors: Yamashita Hironobu , Kawasawa Yuka Imamura , Shuman Lauren , Zheng Zongyu , Tran Truc , Walter Vonn , Warrick Joshua I. , Al-Ahmadie Hikmat , Kaag Matthew , Wong Pak Kin , Raman Jay D. , DeGraff David J.
Published: September 2018

The discovery of bladder cancer transcriptional subtypes provides an opportunity to identify high risk patients, and tailor disease management. Recent studies suggest tumor heterogeneity contributes to “plasticity” of molecular subtype during progression and following treatment. Nonetheless, the transcriptional drivers of the aggressive basal-squamous subtype remain unidentified. As PPARγ has been repeatedly implicated in the luminal subtype of bladder cancer, we hypothesized inactivation of this transcriptional master regulator during progression results in increased expression of basal-squamous specific transcription factors (TFs) which act to drive aggressive behavior. We initiated a pharmacologic and RNA-seq-based screen to identify PPARγ-repressed, basal-squamous specific TFs. Hierarchical clustering of RNA-seq data following treatment of a panel of human bladder cancer cell lines with a PPARγ agonist identified a number of TFs regulated by PPARγ activation, several of which are implicated in urothelial and squamous differentiation. One PPARγ-repressed TF implicated in squamous differentiation identified is Transcription Factor Activating Protein 2 alpha (TFAP2A). We show TFAP2A and its paralog TFAP2C are overexpressed in basal-squamous bladder cancer and in squamous areas of cystectomy samples, and that overexpression is associated with increased lymph node metastasis and distant recurrence, respectively. Biochemical analysis confirmed the ability of PPARγ activation to repress TFAP2A, while PPARγ antagonist studies indicate the requirement of a functional receptor. In vivo tissue recombination studies show TFAP2A and TFAP2C promote tumor growth in line with the aggressive nature of basal-squamous bladder cancer. Our findings suggest PPARγ inactivation, as well as TFAP2A and TFAP2C overexpression cooperate with other TFs to promote the basal-squamous transition.
Improved high-quality genome assembly and annotation of Tibetan hulless barley
Authors: Zeng Xingquan , Li Xiangfeng , Bai Lijun , Wang Yulin , Xu Tong , Yuan Hongjun , Xu Qijun , Zha Sang , Wei Zexiu , Qimei Wangmu , Basang Yuzhen , Dunzhu Jiabu , Yu Mingzai , Nyima Tashi
Published: September 2018

Background

The Tibetan hulless barley (Hordeum vulgare L. var. nudum), also called “Qingke” in Chinese and “Ne” in Tibetan, is the staple food for Tibetans and an important livestock feed in the Tibetan Plateau. The Tibetan hulless barley in China has about 3500 years of cultivation history, mainly produced in Tibet, Qinghai, Sichuan, Yunnan and other areas. In addition, Tibetan hulless barley has rich nutritional value and outstanding health effects, including the beta glucan, dietary fiber, amylopectin, the contents of trace elements, which are higher than any other cereal crops.

Findings

Here, we reported an improved high-quality assembly of Tibetan hulless barley genome with 4.0 Gb in size. We employed the falcon assembly package, scaffolding and error correction tools to finish improvement using PacBio long reads sequencing technology, with contig and scaffold N50 lengths of 1.563Mb and 4.006Mb, respectively, representing more continuous than the original Tibetan hulless barley genome nearly two orders of magnitude. We also re-annotated the new assembly, and reported 61,303 stringent confident putative protein-coding genes, of which 40,457 is HC genes. We have developed a new Tibetan hulless barley genome database (THBGD) to download and use friendly, as well as to better manage the information of the Tibetan hulless barley genetic resources.

Conclusions

The availability of new Tibetan hulless barley genome and annotations will take the genetics of Tibetan hulless barley to a new level and will greatly simplify the breeders effort. It will also enrich the granary of the Tibetan people.