bluuebunny/crossref_metadata_2025_split huggingface dataset:
Imaging mass spectrometry for the precise design of antibody-drug conjugates
Authors: Fujiwara Yuki , Furuta Masaru , Manabe Shino , Koga Yoshikatsu , Yasunaga Masahiro , Matsumura Yasuhiro 
Published: April 2016

AbstractAntibody-drug conjugates (ADCs) are a class of immunotherapeutic agents that enable the delivery of cytotoxic drugs to target malignant cells. Because various cancers and tumour vascular endothelia strongly express anti-human tissue factor (TF), we prepared ADCs consisting of a TF-specific monoclonal antibody (mAb) linked to the anticancer agent (ACA) monomethyl auristatin E (MMAE) via a valine-citrulline (Val-Cit) linker (human TF ADC). Identifying the most efficient drug design in advance is difficult because ADCs have complicated structures. The best method of assessing ADCs is to examine their selectivity and efficiency in releasing and distributing the ACA within tumour tissue. Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) can be used to directly detect the distributions of native molecules within tumour tissues. Here, MALDI-IMS enabled the identification of the intratumour distribution of MMAE released from the ADC. In conclusion, MALDI-IMS is a useful tool to assess ADCs and facilitate the optimization of ADC design.
The Regenerative Potential of Notochordal Cells in a Nucleus Pulposus Explant
Authors: Arkesteijn Irene T. M. , Potier Esther , Ito Keita 
Published: April 2016

Study Design In vitro disk explant culture. Objective Notochordal cells (NCs) have been shown to upregulate matrix production by nucleus pulposus (NP) cells in coculture. To examine the translation of these in vitro results to a nativelike setting, the regenerative potential of NCs injected into NP tissue was assessed in this study. Methods NP explants were cultured after injection with NCs in phosphate-buffered saline (PBS) or with PBS alone (sham). At days 0 and 42, cell viability and morphology, water, DNA, sulfated glycosaminoglycan and hydroxyproline content, and gene expression of anabolic markers were analyzed. Results NCs remained viable during culture, but their morphology changed. The biochemical content remained unchanged, except for the DNA content in the NC group. Overall ACAN expression remained unchanged, whereas COL2A1 decreased during culture. Conclusions No overall anabolic response was observed when NCs were injected into NP explants. NCs were found to survive but did not display the typical NC morphology by the end of the culture period.
Liquid–liquid phase transition in hydrogen by coupled electron–ion Monte Carlo simulations
Authors: Pierleoni Carlo , Morales Miguel A. , Rillo Giovanni , Holzmann Markus , Ceperley David M. 
Published: April 2016

Significance
Understanding hydrogen metallization under pressure and its interplay with molecular dissociation is still a major challenge in high-pressure and fundamental physics. We report results of quantum Monte Carlo simulations that indicate that the two phenomena occur simultaneously through a first-order phase transition in fluid hydrogen at megabar pressures and temperatures of 1,000 K. The predicted pressures are close to claims of metallization based on static compression experiments but are lower than that of recent dynamic compression measurements. The simulation results represent the most reliable theoretical prediction yet of the liquid–liquid transition in hydrogen and provide constraints for future experiments.
The Victorian Novel Dreams of the Real
Authors: Jaffe Audrey 
Published: April 2016

Abstract
The Victorian Novel Dreams of the Real argues that Victorian novelistic realism is a product of the Victorians’ overarching desire, both cultural and ideological, for the real. What the book calls “realist fantasy” describes the way in which the conventions used to represent characters’ dreams, daydreams, and fantasies also shape the more general and generalized fantasy that constitutes each particular novel’s imagining of the real. In readings of George Eliot’s Adam Bede, Dickens’s Oliver Twist, Hardy’s Mayor of Casterbridge, Trollope’s Orley Farm, and Wilkie Collins’s Armadale, the book demonstrates that realism and fantasy in these novels are not opposed, but rather occupy the same space and are constructed via the same conventions. Refusing to distinguish their objects of knowledge from their objects of desire, the novels invite readers to do the same. The book’s contention that Victorian fiction builds on a general nineteenth-century desire for the real draws on the way the structure of Victorian ideologies—about, for example, domesticity, character, gender, nationality, and the possibility of objectivity—support the Althusserian and Lacanian account of ideology as an “imaginary relationship to the real conditions of existence,” with the term “imaginary” defined not as an escape from the real but rather as the real, insofar as that is the name given to the institutions and structures that invest ideology with the substance and solidity the Victorians prized.
“Outside the Gates of Everything”
Authors: Jaffe Audrey 
Published: April 2016

Abstract
This chapter discusses the use of space to both include and exclude characters and readers in Hardy’s The Return of the Native, Jude the Obscure, and The Woodlanders. It includes a revisionary account of metonymy and a redefinition of realism’s use of landscape, arguing that realist representation returns to the reader/spectator an affirming reflection of him/herself, while at the same time excluding those who do not see themselves in these same surroundings. In this reading, realist conventions typically seen as making a space for, and defining, a novel’s characters and readers—conventions such as metonymy and ideological structures such as interpellation—are indistinguishable from a character’s fantasy that the world is paying particular attention to him. Hardy exposes the real as bounded: a space that includes and excludes.
Armadale
Authors: Jaffe Audrey 
Published: April 2016

Abstract
This chapter discusses Wilkie Collins’s use of the idea of the real—including allusions to a real ship named The Armadale and a desire on the part of his sensational characters to live realist lives--to anchor this sensation novel The novel centers on the interpretation of a dream, and the chapter includes discussion of the way Freud’s dream theory, like Armadale itself, presents the dreamer as a vehicle for transforming one genre into another, forging sensational dramas from the banal details of everyday life. It includes an extended account of the ostensible difference between character in sensation fiction—defined according to role or position—and realist character, defined as unique and possessing interiority, proposing that Armadale’s sensational characters long to be realist ones.
Tractarian Geometry
Authors: Turner Jason 
Published: April 2016

AbstractIf the facts are arranged in a logical space, it must have a quasi-geometric structure. This chapter axiomatizes that quasi-geometry. Tractarian geometry has two kinds of geometric structures: quality spaces and hypersurfaces. The axioms use two primitive quasi-geometric notions, one for each kind of structure. Results are proven about the resulting geometry, culminating in the Predicational Determination Theorem, which says that any fact can be uniquely located by a single quality space and a sequence of hypersurfaces.
Modality
Authors: Turner Jason 
Published: April 2016

AbstractCombinatorial theories of modality aim to understand possibility and necessity as being about how reality’s basic building blocks do and don’t fit together. Factalism is well-suited to such a theory, as it can identify ‘basic building blocks’ with the facts. The factalist’s simplest combinatorial theory vindicates necessitism—the view that whatever can exist does so necessarily—and faces the ‘colour-exclusion problem’. Several strategies for solving the colour-exclusion problem are outlined. Some give up on reductive ambitions, and some do not. The virtues and vices of necessitism are also discussed, and some methods for avoiding necessitism while endorsing an combinatorial analysis are outlined.
Alternatives and Applications
Authors: Turner Jason 
Published: April 2016

AbstractTractarian factalism treats facts as occupying a logical space. That space can be considered in three ways, familiar from discussions of ordinary spaces. The dualist picture holds that there are two kinds of things: points and their occupants. Relationalism rejects the points and keeps the occupants; supersubstantivalism rejects the occupants and keeps the points. This chapter examines how factalism looks on each of these three understandings. It further examines whether the factalist’s facts can serve as truthmakers. Factalism is then abandoned, and the resources of Tractarian geometry are applied to monism, the view that there is only one ultimate (concrete) thing, and to Ontological Nihilism, the view that there is absolutely nothing at all.
Latent Class Analysis of Neurodevelopmental Deficit After Exposure to Anesthesia in Early Childhood
Authors: Ing Caleb , Wall Melanie M. , DiMaggio Charles J. , Whitehouse Andrew J.O. , Hegarty Mary K. , Sun Ming , von Ungern-Sternberg Britta S. , Li Guohua , Sun Lena S. 
Published: April 2016

Introduction:
Although some studies have reported an association between early exposure to anesthesia and surgery and long-term neurodevelopmental deficit, the clinical phenotype of children exposed to anesthesia is still unknown.

Methods:
Data were obtained from the Western Australian Pregnancy Cohort Study (Raine) with neuropsychological tests at age 10 years measuring language, cognition, motor function, and behavior. Latent class analysis of the tests was used to divide the cohort into mutually exclusive subclasses of neurodevelopmental deficit. Multivariable polytomous logistic regression was used to evaluate the association between exposure to surgery and anesthesia and each latent class, adjusting for demographic and medical covariates.

Results:
In our cohort of 1444 children, latent class analysis identified 4 subclasses: (1) Normal: few deficits (n=1135, 78.6%); (2) Language and Cognitive deficits: primarily language, cognitive, and motor deficits (n=96, 6.6%); (3) Behavioral deficits: primarily behavioral deficits, (n=151, 10.5%); and (4) Severe deficits: deficits in all neuropsychological domains (n=62, 4.3%). Language and cognitive deficit group children were more likely to have exposure before age 3 (adjusted odds ratio [aOR], 2.11; 95% confidence interval [CI], 1.17-3.81), whereas a difference in exposure was not found between Behavioral or Severe deficit children (aOR, 1.00; 95% CI, 0.58-1.73, and aOR, 0.85; 95% CI, 0.34-2.15, respectively) and Normal children.

Conclusions:
Our results suggest that in evaluating children exposed to surgery and anesthesia at an early age, the phenotype of interest may be children with deficits primarily in language and cognition, and not children with broad neurodevelopmental delay or primarily behavioral deficits.
Chen’s Double Eyelid Fold Ratio
Authors: Chen Chen-Chia , Tai Hao-Chih , Huang Chien-Lin 
Published: April 2016

Background:
Double eyelidplasty can construct palpebral folds and enhance beauty perception for Asians with single eyelids. A new palpebral parameter for the quantitative interpretation of surgical outcomes is proposed on the basis of a photometric study of the altered proportions of Asian eyes after double eyelid operation.

Methods:
A total of 100 Asian adults with single upper eyelids who were satisfied with the enlarged eyes by operation were included in the study. A retrospective measurement of palpebral parameters in the frontal profile both preoperatively and 6 months postoperatively was performed. The proportions of various parameters in the eyebrow–eye aesthetic unit were calculated and analyzed.

Results:
Double eyelidplasty can augment the vertical dimension of palpebral fissure by 27.9% increase on average. The vertical ratio of palpebral fissure to the eyebrow–eye unit is augmented by 34.4% increase. The vertical ratio of the subunit below double eyelid fold peak to the unit is augmented by 82.6% increase.

Conclusions:
Double eyelidplasty can substantially enlarge the vertical dimensions of the eyes of Asians with single eyelids. The eyes are perceived to be larger because of the visually assimilated illusion of the superimposed eyelid fold and the relative proportions of the eyebrow–eye unit. The authors propose using a vertical ratio of the subunit below double eyelid fold peak in the eyebrow–eye unit to measure the visually perceived proportion of the eye in the unit. This ratio can be applied clinically for a quantitative evaluation of the surgical outcome after double eyelidplasty.
Robotic Endoscopic Off-Pump Total Pericardiectomy in Constrictive Pericarditis
Authors: Maciolek Kimberly , Asfaw Zewditu E. , Krienbring Dorothy J. , Arnsdorf Susan E. , Balkhy Husam H. 
Published: April 2016

Objective Although rare, constrictive pericarditis is a serious condition with debilitating symptoms and often severe heart failure. Total pericardiectomy is the most effective treatment and is traditionally performed via median sternotomy. With the increasing use of minimally invasive techniques, there have been reports of partial pericardiectomy via thoracoscopy but with suboptimal exposure and difficulty identifying both phrenic nerves. Robotic surgery offers both small incisions and enhanced visualization. We present four cases of robotic endoscopic off-pump total pericardiectomy for constrictive pericarditis. Methods Four patients underwent off-pump total pericardiectomy with robotic assistance for constrictive pericarditis. All had constrictive physiology demonstrated by right heart catheterization and/or echo-cardiogram. One was also found to have coronary artery disease and underwent concurrent totally endoscopic coronary artery bypass grafting left internal mammary artery to left anterior descending artery. Ports were placed in the left second, fourth, and sixth intercostal spaces. The left lung was isolated and deflated with CO2 insufflation, aiding in exposure. With the use of electrocautery, the pericardium was removed first posterior to the left phrenic nerve, then anteriorly all the way to the right phrenic nerve, and caudally from the diaphragmatic reflection to the great vessel cephalad. A stabilizer in the subcostal fourth robotic arm was used to assist in the dissection. Results Two of four patients were extubated within 6 hours after surgery and transferred to the floor on postoperative day 1. Both were discharged home by postoperative day 5. Two of four patients had preoperative sequelae from chronic constriction and necessitated longer hospital and intensive care unit stays but had improvement in symptoms and were discharged home within 3 weeks. Conclusions Total pericardiectomy for constrictive pericarditis can be performed using a robotic approach. In contrast to thoracoscopy, it offers better visualization of both phrenic nerves, avoids injury, and allows a thorough pericardial dissection. In our experience, the robotic left chest approach has proven more efficacious in removing the posterior pericardium than is allowed with median sternotomy.
Paradoxical articular manifestations in patients with inflammatory bowel diseases treated with infliximab
Authors: Thiebault Henri , Boyard-Lasselin Pauline , Guignant Caroline , Guillaume Nicolas , Wacrenier Adrien , Sabbagh Charles , Rebibo Lionel , Brazier Franck , Meynier Jonathan , Nguyen-Khac Eric , Dupas Jean-Louis , Goëb Vincent , Fumery Mathurin 
Published: April 2016

Introduction
Articular involvement is the most common extraintestinal manifestation associated with inflammatory bowel diseases (IBDs). Manifestations are ‘paradoxical’ when they occur during treatment, notably with anti-tumor necrosis factor (anti-TNF) drugs, which are expected to prevent or treat them. The aim of this study was to assess the frequency, characteristics, and associated factors of paradoxical articular manifestations in patients with IBD treated with anti-TNF.

Patients and methods
In this prospective single-center study, an examination by a rheumatologist was systematically offered to all patients with IBD treated with infliximab (IFX) to assess the prevalence of articular manifestations and distinguish between those related to treatment and those associated with intestinal disease. Paradoxical manifestations were defined as the occurrence of articular manifestations (excluding induced lupus and hypersensitivity reactions) during anti-TNF therapy in patients with intestinal remission. Measures of biological inflammatory, immunological markers, HLA-B27 allele, IFX trough levels, and anti-IFX antibody (Ab) were performed for all patients.

Results
Between May 2013 and April 2014, 65 patients with Crohn’s disease and 15 with patients ulcerative colitis treated with IFX were included. The median duration of anti-TNF therapy was 66 months [quartile (Q)1=23 months–Q3=81 months]. Articular manifestations were observed in 50 (62%) patients treated with IFX. Eleven percent (n=9) were considered to be associated with IBD and 16% (n=13) to be associated with anti-TNF therapy. Among articular manifestations associated with anti-TNF therapy, nine (11%) patients were considered paradoxical, two (2%) as drug-induced lupus, and two (2%) as a hypersensitivity reaction. Among the nine patients with paradoxical manifestations, all had Crohn’s disease in clinical remission, three patients presented a spondyloarthropathy, and three developed associated paradoxical psoriasis. No patient discontinued anti-TNF because of the articular manifestations. Methotrexate was effective on articular symptoms in two of the three treated patients with paradoxical manifestations. No clinical or biological factors, including IFX trough levels, were associated with the occurrence of paradoxical manifestations.

Conclusion
Paradoxical articular manifestations in IBD patients treated by anti-TNF are common, affecting more than 10% of patients. These events are generally mild and do not need discontinuation of anti-TNF therapy.
Histiocytic neoplasms in the era of personalized genomic medicine
Authors: Durham Benjamin H. , Diamond Eli L. , Abdel-Wahab Omar 
Published: April 2016

Purpose of reviewSince the discovery of B-Raf proto-oncogene (BRAF) V600E mutations in histiocytic neoplasms, diverse kinase alterations have been uncovered inBRAFV600E-wildtype histiocytoses. The purpose of this review is to outline recent molecular advances in histiocytic neoplasms and discuss their impact on the pathogenesis and treatment of these disorders.Recent findingsActivating kinase alterations discovered inBRAFV600E-wildtype Langerhans (LCH) and non-Langerhans cell histiocytoses (non-LCH) result in constitutive activation of the mitogen-activated protein kinase and/or phosphoinositide 3-kinases-Akt murine thymoma pathways. These kinase alterations include activating mutations in A-Raf proto-oncogene, mitogen-activated protein kinase kinase 1, neuroblastoma rat sarcoma viral oncogene homolog, Kirsten rat sarcoma viral oncogene homolog, and phosphatidylinositol-4,5-bisphosphate 3 kinase, catalytic subunit α kinases in LCH and non-LCH;BRAF, anaplastic lymphoma receptor tyrosine kinase, and neurotrophic tyrosine kinase, receptor type 1 fusions, as well as the Ets variant 3-nuclear receptor coactivator 2 fusion in non-LCH; and mutations in the mitogen-activated protein kinase kinase kinase 1 and Harvey rat sarcoma viral oncogene homolog kinases in LCH and histiocytic sarcoma, respectively. These discoveries have refined the understanding of the histiocytoses as clonal, myeloid neoplasms driven by constitutive mitogen-activated protein kinase signaling and identified molecular therapeutic targets with promising clinical responses to rapidly accelerated fibrosarcoma and mitogen-activated protein kinase kinase inhibition.SummaryGenomic analyses over the last 6 years have identified targetable kinase alterations inBRAFV600E-wildtype histiocytic neoplasms. However, despite this progress, the molecular pathogenesis and therapeutic responsiveness of non-BRAFV600E kinase alterations are still poorly defined in these disorders.
Cell autonomous and microenvironmental regulation of tumor progression in precursor states of multiple myeloma
Authors: Manier Salomon , Kawano Yawara , Bianchi Giada , Roccaro Aldo M. , Ghobrial Irene M. 
Published: April 2016

Purpose of review
Multiple myeloma is a plasma cell malignancy evolving in the bone marrow and leading to end organ damage such as bone lesions, cytopenias, and kidney failure. This review delineates recent advances in the molecular mechanisms leading to tumor progression in multiple myeloma. Two different aspects enable tumor expansion: cell autonomous through genomic alterations in the tumor clone and noncell autonomous deregulations in the bone marrow tumor microenvironment. These alterations provide the framework for the continuous progression of multiple myeloma from early precursor conditions such as monoclonal gammopathy of undetermined significance and smoldering multiple myeloma to overt multiple myeloma.

Recent findings
In this review, we discuss recent findings in the genomic alterations that occur in the tumor clone such as somatic genomic mutations, copy number variation and chromosomal translocation, and delineate noncell autonomous deregulations in which tumor cells take advantage of a permissive microenvironment to further proliferate. The latter compartment includes interaction with bone marrow stromal cells, osteoblasts, osteoclasts, and immune escape.

Summary
Understanding the mechanisms that lead tumor progression from early stages to overt multiple myeloma could guide to more effective therapies and therefore prevent disease progression.
Knowledge and Attitudes About Attention-Deficit/Hyperactivity Disorder and Specific Learning Disorder in an Urban Indian Population
Authors: Mukherjee Sayantani , Shah Henal R. , Ramanathan Seethalakshmi , Dewan Mantosh 
Published: April 2016

AbstractAttention-deficit/hyperactivity disorder (ADHD) and specific learning disorders (SLDs) are an important cause of scholastic backwardness among children and often go unrecognized. Few studies have examined knowledge and attitudes toward ADHD and SLD among school-aged children. To address this deficit, 120 school-aged children, attending a child guidance clinic in Mumbai, were interviewed using a questionnaire that examined children’s knowledge and attitudes about ADHD and SLD. The results were compared both qualitatively and quantitatively with a frequently occurring medical illness, common cold. Approximately 80% to 100% of children were aware of their illness; however, a large variation was noted in the proportion of children (15%–80%) who could describe their symptoms, provide accurate attributions for their illness, and identify treatment modalities. Children with ADHD reported greater control over their illness. The study identified a significant lack of knowledge about ADHD and SLD among school-aged children in India and discusses implications of this finding.