bluuebunny/crossref_metadata_2025_split huggingface dataset:
FGFR3 overexpression is a useful detection tool for FGFR3 fusions and sequence variations in glioma
Authors: Schittenhelm Jens , Ziegler Lukas , Sperveslage Jan , Mittelbronn Michel , Capper David , Burghardt Isabel , Poso Antti , Biskup Saskia , Skardelly Marco , Tabatabai Ghazaleh 
Published: January 2021

Abstract

Background
Fibroblast growth factor receptor (FGFR) inhibitors are currently used in clinical development. A subset of glioblastomas carries gene fusion of FGFR3 and transforming acidic coiled-coil protein 3. The prevalence of other FGFR3 alterations in glioma is currently unclear.

Methods
We performed RT-PCR in 101 glioblastoma samples to detect FGFR3-TACC3 fusions (“RT-PCR cohort”) and correlated results with FGFR3 immunohistochemistry (IHC). Further, we applied FGFR3 IHC in 552 tissue microarray glioma samples (“TMA cohort”) and validated these results in two external cohorts with 319 patients. Gene panel sequencing was carried out in 88 samples (“NGS cohort”) to identify other possible FGFR3 alterations. Molecular modeling was performed on newly detected mutations.

Results
In the “RT-PCR cohort,” we identified FGFR3-TACC3 fusions in 2/101 glioblastomas. Positive IHC staining was observed in 73/1024 tumor samples of which 10 were strongly positive. In the “NGS cohort,” we identified FGFR3 fusions in 9/88 cases, FGFR3 amplification in 2/88 cases, and FGFR3 gene mutations in 7/88 cases in targeted sequencing. All FGFR3 fusions and amplifications and a novel FGFR3 K649R missense mutation were associated with FGFR3 overexpression (sensitivity and specificity of 93% and 95%, respectively, at cutoff IHC score &gt; 7). Modeling of these data indicated that Tyr647, a residue phosphorylated as a part of FGFR3 activation, is affected by the K649R mutation.

Conclusions
FGFR3 IHC is a useful screening tool for the detection of FGFR3 alterations and could be included in the workflow for isocitrate dehydrogenase (IDH) wild-type glioma diagnostics. Samples with positive FGFR3 staining could then be selected for NGS-based diagnostic tools.
Colistin Nephrotoxicity: Meta-Analysis of Randomized Controlled Trials
Authors: Eljaaly Khalid , Bidell Monique R , Gandhi Ronak G , Alshehri Samah , Enani Mushira A , Al-Jedai Ahmed , Lee Todd C 
Published: January 2021

Abstract

Background
Nephrotoxicity is a known adverse effect of polymyxin antibiotics, including colistin. Although previous meta-analyses have aimed to characterize colistin-associated nephrotoxicity risk relative to other antibiotics, included studies were observational in nature with high risk of confounding and heterogeneity. We conducted this systematic review and meta-analysis of exclusively randomized controlled trials (RCTs) to evaluate the incidence of nephrotoxicity associated with colistin versus minimally nephrotoxic antibiotics.

Methods
We searched PubMed, EMBASE, Cochrane Library, and 3 trial registries for RCTs comparing the nephrotoxicity of colistin to nonpolymyxin antibiotics. Randomized controlled trials that used aminoglycosides were excluded. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using random-effects models. The study outcome was the rate of nephrotoxicity.

Results
Five RCTs with a total of 377 patients were included. Most patients received colistin for pneumonia in the intensive care unit, and the comparators were β-lactam-based regimens. Colistimethate sodium was dosed at 9 million units/day (300 mg/day of colistin base activity), with administration of a loading dose in 4 studies. The nephrotoxicity incidence in patients who received colistin was 36.2% (95% CI, 23.3% to 51.3%). The nephrotoxicity rate was significantly higher in the colistin arm than comparators (RR, 2.40; 95% CI, 1.47 to 3.91; P ≤ .001; I2 = 0%), and the number needed to harm was 5. Findings persisted upon one-study-removed-analysis.

Conclusions
This meta-analysis of RCTs found a colistin-associated nephrotoxicity rate of 36.2% and an increase in this risk compared with β-lactam-based regimens by 140%. Colistin should be regarded as a last-line agent and safer alternatives should be considered when possible.
Sternberg's Canal and Defect: Is the Lateral Craniopharyngeal Canal a Source of Spontaneous Cerebrospinal Fluid Leak? Anatomic and Radiological Analysis in Pediatric and Adult Populations
Authors: Adepoju Adedamola , Carlstrom Lucas P , Graffeo Christopher S , Perry Avital , Pinheiro-Neto Carlos Diogenes , Link Michael J , Peris-Celda Maria 
Published: January 2021

Abstract

BACKGROUND
The lateral craniopharyngeal or Sternberg's canal (SC) originates from superior orbital fissure (SOF) and traverses the sphenoid body into the nasopharynx. A remnant of the canal, Sternberg's defect (SD), has been debated as a source of cerebrospinal fluid (CSF) leak. The canal was described in 1888, and there is limited accurate visual illustration in the literature.

OBJECTIVE
To provide a detailed anatomic and radiological illustration of the canal in pediatric and adult population including the mechanism undermining the incidence of the canal, and the possibility of the canal as a source of CSF leak.

METHODS
A total of 195 high-resolution computed tomographies (CT) of patients (50 3-yr-old, 20 5-yr-old, and 125 adults) and 43 dry adult skulls (86 sides) were analyzed for a canal matching the description of the SC.

RESULTS
A SC was identified in 86% of the 3-yr-old and 40% of 5-yr–old patients. The diameter and length were 2.12 mm and 12 mm, respectively. The incidence of the canal decreased with age as sinus pneumatization extended into the sphenoid sinus. Only 0.8% of the adult skull on CT had the canal. The canal was not present on the dry adult skulls examination, but SD was found in 4.65%.

CONCLUSION
SC exists with high incidence in the pediatric group. Sinus pneumatization obliterates the canal in the adult population, leaving a defect in 4.65% of cases, which given the location and related anatomic structures, is unlikely to be a source of CSF leak.
Assessing Transhumanist Advocacy of Cognitive Bioenhancement
Authors: Levin Susan B. 
Published: January 2021

AbstractThough they condemn the “essentialism” of their critics, transhumanists themselves embrace rational essentialism. Transhumanists’ extreme version includes outright hostility to the nonrational in the form of “negative” affect, above all, emotion and mood. This dismissal reflects an impoverished picture of our mental life and problematizes transhumanists’ own investment in cognitive bioenhancement. Transhumanists link themselves to a rich philosophical tradition when foregrounding reason as the linchpin of our humanity. When considering its augmentation, however, they conflate “reason” and “cognition.” Since transhumanists define “cognition” in terms of information, forms of rational engagement not reducible to its possession and manipulation are unaccounted for. Practically speaking, transhumanists wrongly take supposed enhancing effects of existing psychostimulants as a clear harbinger of far more powerful cognitive bioenhancers. Even if we limit ourselves to what transhumanists envision under cognitive bioenhancement, their confidence in the direct, unadulterated heightening of cognition is misguided.
Ambiguities of the Priesthood
Authors: McManus Laurie 
Published: January 2021

Abstract
The unstable category of priesthood brought with it ambiguities and sometimes unfortunate implications. For Brahms the bachelor, whose own performances garnered occasional feminized rhetoric even from Eduard Hanslick, the priesthood could be interpreted as an avoidance of sexuality. This chapter contextualizes art-religious rhetoric of asceticism and martyrdom with burgeoning psychological approaches to artistic identity, including Max Klinger’s own psychological interpretation of the martyr Prometheus in his Brahms-Phantasie. Priestly abstinence is then contextualized with contemporary notions of chastity seen in Paolo Mantegazza’s studies of sexuality and with Friedrich Nietzsche’s ascetic ideals. The author suggests that, on one level, some of Brahms’s most heteronormative supporters such as Philipp Spitta and Josef Viktor Widmann wrote masculinized rhetoric in response to these negative implications.
The Middle Way
Authors: Chollet Derek 
Published: January 2021

Abstract
This book explores the shared foreign policy legacies of Dwight Eisenhower, George H. W. Bush, and Barack Obama, and how they exemplify a distinct and underappreciated tradition of political leadership: the Middle Way. The book explores how these three presidents thought about the world and American leadership, and how they grappled with foreign policy crises and navigated politics. Drawing upon new archival research at the Eisenhower and Bush presidential libraries, and interviews with former Obama officials, the book shows how these presidents took a centrist approach to foreign policy and provides a model for America to reinvigorate its role as a global leader. This work of presidential history looks behind the scenes at some of the most important moments in foreign policy since World War II, and it explores the broader lessons for American foreign policy and leadership. The book reflects the author’s unique experience as a senior official at the White House, the State Department, and the Pentagon to show how Washington, DC, works from the inside; and in the process, offers a new way of thinking about American global leadership and makes a case for new ways to measure presidential success.
Introduction
Authors: Chollet Derek 
Published: January 2021

Abstract
This chapter explores the centrist tradition that unites Eisenhower, H. W. Bush, and Obama, revealing a distinct foreign policy lineage forged by presidents who served during inflection points in American history. It summarizes the Middle Way as an outlook and draws the connections between these three presidents. Finally, it previews the five different angles of statecraft—worldview, strategy, crisis, politics, and legacy—the book uses to study the thematic similarities between each president’s approach to foreign policy.
Strategy
Authors: Chollet Derek 
Published: January 2021

Abstract
This chapter explores what Eisenhower, H. W. Bush, and Obama set out to achieve in foreign policy—explaining the initial strategic choices they made once in office, how they formulated them, and what influenced their thinking. It analyzes Eisenhower’s effort to build a foundation for US foreign policy in the early Cold War years and devise a sustainable concept of containment; Bush’s attempts to understand the nature of change in the Soviet Union and the possibilities for superpower cooperation, especially how to define American foreign policy after the Cold War; and Obama’s work to promote a foreign policy based on “smart power” and to “rebalance” US foreign policy to address twenty-first-century geopolitical shifts after inheriting a catastrophic economic crisis at home.
Legacy
Authors: Chollet Derek 
Published: January 2021

Abstract
This chapter discusses the legacies that Eisenhower, H. W. Bush, and Obama left behind. It traces how perceptions of these presidents changed over time and evaluates how their example of leadership stands in history’s light, making the case for the enduring relevance of the Middle Way. It subsequently extrapolates lessons these presidents offer for presidential leadership and US foreign policy today: recognizing the limits of power; appreciating the value of incremental change, rewarding strategic foresight, maintaining tragic optimism, embracing moderation as a virtue.
Subterranean and Anchialine Waters
Authors: Bishop Renée E. , Humphreys William , Jaume Damià 
Published: January 2021

Abstract
Crustaceans have successfully colonized the subterranean habitat, and many have become obligate inhabitants, occurring virtually everywhere there are interconnected voids underground. With the exception of most oniscidean isopods and a few talitrid amphipods, subterranean crustaceans inhabit water (stygobionts), where they dominate the stygofauna both in biomass and diversity of species. Four major taxonomic groups predominate: amphipods, isopods, copepods, and ostracods. Although most higher crustacean taxa have representatives in both epigean and subterranean habitats, some groups such as remipedes, thermosbaenaceans, spelaeogriphaceans, bathynellaceans, mystacocarids, and gelyelloid copepods are known only from the subterranean environment. Subterranean habitats vary physically and range from organically rich shallow habitats around seeps to cave systems more than a kilometer deep. Water quality, which can range from fresh to marine to hypersaline, static to flowing, and oxic to suboxic, impacts species distribution. Dispersal patterns in subterranean crustaceans are also diverse. Freshwater stygobiont crustaceans have narrow endemic ranges, and their dispersal is limited by saltwater. The distribution of several freshwater taxa might reflect the movement of tectonic plates. The extraordinarily diverse anchialine fauna, initially distributed along the Tethyan coast, was likely spread by vicariance due to movement of tectonic plates. Originating from epigean ancestors, many stygobionts have a marine origin. While the existence of preadaptations does not necessarily guarantee successful colonization of the subterranean habitat, a suite of characteristics is frequently observed in subterranean crustaceans, with most being weakly chitinized, lacking or with reduced eyes and pigments, and enhanced non-optic sense organs. Metabolic rates tend to be lower than in epigean crustaceans. Limited evidence indicates subterranean crustaceans are longer lived with lower reproductive potential. These adaptations make subterranean crustacean populations particularly vulnerable to anthropogenic impacts. The morphological, physiological, and life history adaptations to a subterranean existence are most likely common responses to the physical environment of each subterranean ecosystem. Extensive biodiversity and phylogeography studies are still required, and there is a pressing need to comprehend the functional role of stygofauna in subterranean waters.
Impossibilities, Normalized
Authors: Swenson Kristin 
Published: January 2021

Abstract
This chapter examines biblical oddities and assumptions. There are two general categories of biblical oddity: the matter-of-fact weird and the admittedly weird. The first category comprises peculiarities and strange events that biblical texts report without any notice of the fact that they are extraordinary. The second contains peculiarities that the Bible draws attention to as peculiar. Without resorting to one-size-fits-all scientific explanations or simply explaining away the Bible's oddities with modern arrogance, this chapter helps readers get a handle on the whys and wherefores of the Bible's miracles and its reason-defying assumptions, appreciating how they may have come to be, the roles they play, and the ways that one might either make sense of them today or simply recognize them for their very strangeness.
Biblical (Im)Morality
Authors: Swenson Kristin 
Published: January 2021

Abstract
This chapter considers those instances wherein the Bible espouses questionable ethics. In the process, it shows how the Bible often upends modern expectation. The texts beg us to take a step back and acknowledge that just because something is in the Bible does not make it right. From ethnic cleansing to owning human beings to not-so-Christian family values, the Bible is hardly a transparent model of righteousness through and through. This chapter notes some of those texts, contextualizes them where it is helpful and appropriate to do so, suggests ways besides the prescriptive to think about how one treats those passages, and simply acknowledges that their existence shows that the Bible may not always be what we expect or wish it to be.
The Perennial Bestseller
Authors: Swenson Kristin 
Published: January 2021

Abstract
This chapter presents the ways the Bible has permeated modern culture, especially outside of predictable settings such as synagogues and churches. From characters and poems to sayings and storylines, the Bible provides an astonishing number of expressions, practices, and tropes that still resonate today. The chapter discusses a mere fraction of biblical phrases and imagery that have found their way into modern discourse, making familiar what nevertheless bears surprising peculiarities. Individual characters and stories also show up in reimaginings that are sometimes quite rich and provocative. It is not always necessary to know their biblical origins to appreciate modern usage, but the value of knowing about the Bible, regardless of what one believes, can be a safeguard against the kinds of misuse that cause discord and outright damage.
Introduction
Authors: Heyman Barbara B. 
Published: January 2021

Abstract
Barber began his life as a composer in the 1930s, with his music veering into eighteenth- and nineteenth-century European traditions. There were three major influences in his career. The first was his formal musical education at the newly founded Curtis Institute of Music, which provided a sturdy structure to his work and was also known to be European-oriented. The second was his travels to Europe, where his acquaintances as well as the culture itself were infused into his work. The last influence was the mentoring and guidance of his uncle, composer Sidney Homer, who was married to Barber’s maternal aunt, the famous opera singer Louise Homer. For more than twenty-five years, Sidney Homer had the most profound influence on Barber of all, encouraging him to “listen to his inner voice,” which enabled him to infuse the very soul of his compositions with the romantic passion that ultimately deeply moved his audience.
Beginnings
Authors: Heyman Barbara B. 
Published: January 2021

Abstract
This chapter discusses the roots of Barber’s family in Pennsylvania. He began his music education early in his life. By the time he was six, his various talents were apparent to his parents. However, it was only when Barber was nine years old that he realized his dream was not to be an athlete and go to Princeton as his father, a physician, would have wished, but rather, he wanted to be a composer. His family was supportive of his ambition and urged him to take on further formal studies. His sister, Sara, also was inclined toward music and was one of the first performers of his work. In this chapter, the close relationship between Barber and his uncle Sidney Homer is described; the two spent summers and countless hours together. Barber consulted his uncle about whether music was a good direction to go in for a career. Homer saw the unmistakable talent in the child, and he molded and guided his early compositions. The chapter also discusses Barber’s earliest job as organist for Westminster Church and an elaborate work he composed for the famous organ owned by Pierre du Pont at Longwood Gardens.
Independence
Authors: Heyman Barbara B. 
Published: January 2021

Abstract
This chapter focuses on Barber’s earliest involvement of the performer in the creative process of a composition, in this case the Cello Sonata, premiered by Orlando Cole. The two would meet regularly, with Cole offering suggestions for improvements to the music. This fresh new take in composing music was instantly recognized by friends and audience alike. The founder of the Curtis Institute, Mary Bok, made further efforts in advancing Barber’s and also Gian Carlo Menotti’s careers by conducting auditions with music publishers. This resulted in publications of Barber’s work by G. Schirmer, as well as national radio performances where he was recognized as a pianist, composer, and singer. The chapter also describes Barber’s second large orchestral work, Music for a Scene from Shelley. He also wrote incidental music for a play by Mary Kennedy, One Day of Spring, presented at the Annie Russell Theater in Winter Park, Florida.
The American Academy
Authors: Heyman Barbara B. 
Published: January 2021

Abstract
Barber continued to receive numerous recognitions and awards for his work. In 1935, he was given the Prix de Rome, for being the most talented and promising music student at the time. With the award, he was granted two years of study at the American Academy in Rome, with full lodging and a regular stipend. In this new environment, Barber continued to flourish, winning a Pulitzer traveling scholarship, which provided him with an extended stay at the American Academy, where his fSymphony in One Movement was composed. His uncle, Sidney Homer, proudly observed Barber’s triumphs as he read stories in the local newspaper about his music being performed in America. Uncle and nephew continued to communicate regularly through letters, exchanging queries, comments, and criticisms about Barber’s new compositions. Correspondence between Mary Bok and Barber flourished. Barber wrote many songs on emotionally charged poems, which seem biographically pointed. During the summer, he and Menotti lived in a game warden’s cottage in St. Wolfgang, Austria; there he began work on the String Quartet in B minor, the second movement of which later became the famous Adagio for Strings. Both the symphony and the String Quartet were premiered at the American Academy.
Recognition
Authors: Heyman Barbara B. 
Published: January 2021

Abstract
This chapter describes Barber’s close relationship with Italian conductor Arturo Toscanini. Barber would frequently visit the conductor in his home, most days ending with music. This friendship resulted in Toscanini requesting that Barber write a work for the newly formed NBC Symphony Orchestra. This was a rare privilege, as Toscanini in the past had ignored American composers. His broadcasts were received with much enthusiasm from audiences. Toscanini further advanced Barber’s career by bringing his music to Latin America, with Barber being the first American composer whose work reached those shores. For Toscanini, Barber composed Essay for Orchestra and arranged the second movement of his earlier string quartet as the Adagio for Strings, which brought him international fame and became, as it were, the national funeral music of the United States, associated with the deaths of such famous names as Albert Einstein, Franklin Roosevelt, and Grace Kelly and with the tragedy of September 11, 2001. The chapter also covers Barber’s unaccompanied choral works.
Composer as Conductor
Authors: Heyman Barbara B. 
Published: January 2021

Abstract
With an offer from the London FFRR label to conduct and record his works, including the Medea Suite and the Cello Concerto with Zara Nelsova, Barber studied conducting with Nicolai Malko in Denmark. He bravely took the challenge and was well accepted. Rehearsals proceeded well, and eventually he was invited to Berlin to conduct his Violin Concerto with Charles Turner as soloist. After answering an invitation by Charles Munch to conduct his Second Symphony with the Boston Symphony Orchestra, Barber decided he was “tired of rehearsing his own music.” He believed that good composers did not make good conductors, and he decided to devote all his energy toward his primary creative passion: composing music.