bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antibodies Predict Pegaspargase Allergic Reactions and Failure of Rechallenge
Authors: Liu Yiwei , Smith Colton A. , Panetta John C. , Yang Wenjian , Thompson Lauren E. , Counts Jacob P. , Molinelli Alejandro R. , Pei Deqing , Kornegay Nancy M. , Crews Kristine R. , Swanson Hope , Cheng Cheng , Karol Seth E. , Evans William E. , Inaba Hiroto , Pui Ching-Hon , Jeha Sima , Relling Mary V. 
Published: June 2019

PURPOSE Pegaspargase (PEG-ASP) has largely replaced native Escherichia coli asparaginase (L-ASP) in the treatment of acute lymphoblastic leukemia because of its longer half-life and lower immunogenicity. Risk factors for allergic reactions to PEG-ASP remain unclear. Here, we identify risk factors for reactions in a front-line acute lymphoblastic leukemia trial and assess the usefulness of serum antibodies for diagnosing allergy and predicting rechallenge outcome. PATIENTS AND METHODS PEG-ASP was administered to 598 patients in St Jude’s Total XVI study. Results were compared with Total XV study ( ClinicalTrials.gov identifiers: NCT00549848 and NCT00137111 ), which used native L-ASP. Serum samples (n = 5,369) were analyzed for anti–PEG-ASP immunoglobulin G by enzyme-linked immunosorbent assay. Positive samples were tested for anti–polyethylene glycol (PEG) and anti–L-ASP. We analyzed potential risk factors for reactions and associations between antibodies and reactions, rechallenge outcomes, and PEG-ASP pharmacokinetics. RESULTS Grade 2 to 4 reactions were less common in the Total XVI study with PEG-ASP (81 [13.5%] of 598) than in the Total XV study with L-ASP (169 [41.2%] of 410; P = 1.4 × 10−23). For Total XVI, anti-PEG, not anti–L-ASP, was the predominant component of anti–PEG-ASP antibodies (96%). In a multivariable analysis, more intrathecal therapy (IT) predicted fewer reactions ( P = 2.4 × 10−5), which is consistent with an immunosuppressant contribution of IT. Anti–PEG-ASP was associated with accelerated drug clearance ( P = 5.0 × 10−6). Failure of rechallenge after initial reactions was associated with anti–PEG-ASP ( P = .0078) and was predicted by the occurrence of angioedema with first reaction ( P = .01). CONCLUSION Less IT therapy was the only independent clinical risk factor for reactions to PEG-ASP. PEG, and not L-ASP, is the major antigen that causes allergic reactions. Anti–PEG-ASP has utility in predicting and confirming clinical reactions to PEG-ASP as well as in identifying patients who are most likely to experience failure with rechallenge.
Genomic Instability andTP53Genomic Alterations Associate With Poor Antiproliferative Response and Intrinsic Resistance to Aromatase Inhibitor Treatment
Authors: Schuster Eugene F. , Gellert Pascal , Segal Corrinne V. , López-Knowles Elena , Buus Richard , Cheang Maggie Chon U. , Morden James , Robertson John , Bliss Judith M. , Smith Ian , Dowsett Mitch ,   on behalf of the POETIC Trial Management Group and Trialists
Published: June 2019

PURPOSEAlthough aromatase inhibitor (AI) treatment is effective in estrogen receptor–positive postmenopausal breast cancer, resistance is common and incompletely explained. Genomic instability, as measured by somatic copy number alterations (SCNAs), is important in breast cancer development and prognosis. SCNAs to specific genes may drive intrinsic resistance, or high genomic instability may drive tumor heterogeneity, which allows differential response across tumors and surviving cells to evolve resistance to treatment rapidly. We therefore evaluated the relationship between SCNAs and intrinsic resistance to treatment as measured by a poor antiproliferative response.PATIENTS AND METHODSSCNAs were determined by single nucleotide polymorphism array in baseline and surgery core-cuts from 73 postmenopausal patients randomly assigned to receive 2 weeks of preoperative AI or no AI in the Perioperative Endocrine Therapy—Individualizing Care (POETIC) trial. Fifty-six samples from the AI group included 28 poor responders (PrRs, less than 60% reduction in protein encoded by the MKI67 gene [Ki-67]) and 28 good responders (GdRs, greater than 75% reduction in Ki-67). Exome sequencing was available for 72 pairs of samples.RESULTSGenomic instability correlated with Ki-67 expression at both baseline ( P < .001) and surgery ( P < .001) and was higher in PrRs ( P = .048). The SCNA with the largest difference between GdRs and PrRs was loss of heterozygosity observed at 17p (false discovery rate, 0.08), which includes TP53. Nine of 28 PrRs had loss of wild-type TP53 as a result of mutations and loss of heterozygosity compared with three of 28 GdRs. In PrRs, somatic alterations of TP53 were associated with higher genomic instability, higher baseline Ki-67, and greater resistance to AI treatment compared with wild-type TP53.CONCLUSIONWe observed that primary tumors with high genomic instability have an intrinsic resistance to AI treatment and do not require additional evolution to develop resistance to estrogen deprivation therapy.
Persistently Elevated PTH After Parathyroidectomy at One Year: Experience in a Tertiary Referral Center
Authors: Caldwell Marie , Laux Jeff , Clark Marshall , Kim Lawrence , Rubin Janet 
Published: June 2019

Abstract

Context/Objective
Increased PTH after successful parathyroid surgery represents a clinical conundrum. We aimed to determine the prevalence of persistently elevated PTH (PePTH) postsurgery, along with predisposing factors.

Design
and Setting: Patients ≥ age 18 with parathyroidectomy performed at University of North Carolina Hospitals for primary hyperparathyroidism (PHPT) over a 12-year period were identified from the Carolina Data Warehouse. Clinical and demographic characteristics were collected, transformed, and analyzed.

Results
Five hundred seventy patients met initial criteria for PHPT, and of those 407 had postoperative values. One hundred forty-four had laboratory results within 3 to 18 months post operatively. There was no clinical difference between those with and without long-term laboratory follow-up. Presurgery, patients had average calcium of 11 mg/dL and PTH 125.4 pg/mL. Ninety-seven percent of patients had normalized calcium after surgery, but 30% had PePTH, which can be predicted at 3 months. Patients with PePTH (persistent elevation of PTH) after surgery did not differ from those with normalized PTH in terms of sex, age, body mass index, or excised gland weight; presurgery 25-vitamin D was slightly lower, but not abnormal (26 ± 15 vs 36 ± 11). The presurgical PTH was significantly higher (P &lt; 0.001) in those with PePTH (156.5 pg/mL compared with presurgical level of 102.5 in those whose PTH normalized).

Conclusions
Nearly one-third of PHPT patients have elevated PTH levels postsurgery in a tertiary hospital setting. At presentation, patients with PePTH tend to have higher PTH relative to calcium levels. Whether PePTH after surgical treatment of PHPT has pathological consequences is unknown.
Repair-independent functions of DNA-PKcs protect irradiated cells from mitotic slippage and accelerated senescence
Authors: Liu Yue , Efimova Elena V. , Ramamurthy Aishwarya , Kron Stephen J. 
Published: June 2019

ABSTRACT
The binding of DNA-dependent protein kinase catalytic subunit (DNA-PKcs, also known as PRKDC) to Ku proteins at DNA double-strand breaks (DSBs) has long been considered essential for non-homologous end joining (NHEJ) repair, providing a rationale for use of DNA-PKcs inhibitors as cancer therapeutics. Given lagging clinical translation, we reexamined mechanisms and observed instead that DSB repair can proceed independently of DNA-PKcs. While repair of radiation-induced DSBs was blocked in cells expressing shRNAs targeting Ku proteins or other NHEJ core factors, DSBs were repaired on schedule despite targeting DNA-PKcs. Although we failed to observe a DSB repair defect, the γH2AX foci that formed at sites of DNA damage persisted indefinitely after irradiation, leading to cytokinesis failure and accumulation of binucleated cells. Following this mitotic slippage, cells with decreased DNA-PKcs underwent accelerated cellular senescence. We identified downregulation of ataxia-telangiectasia mutated kinase (ATM) as the critical role of DNA-PKcs in recovery from DNA damage, insofar as targeting ATM restored γH2AX foci resolution and cytokinesis. Considering the lack of direct impact on DSB repair and emerging links between senescence and resistance to cancer therapy, these results suggest reassessing DNA-PKcs as a target for cancer treatment.
Regulation of dendrite morphology and excitatory synapse formation by zDHHC15
Authors: Shah Bhavin S. , Shimell Jordan J. , Bamji Shernaz X. 
Published: June 2019

ABSTRACT
Protein palmitoylation is the most common post-translational lipid modification in the brain and is mediated by a family of 24 zDHHC enzymes. There has been growing interest in zDHHCs due to mounting evidence that these enzymes play key roles in the development and function of neuronal connections, and the fact that a number of zDHHCs have been associated with neurodevelopmental and neurodegenerative diseases. Loss-of-function variants in several zDHHCs, including zDHHC15, have been identified in patients with intellectual disabilities; however, the function of zDHHC15 in the brain has not been well studied. Here, we demonstrate that knocking down zDHHC15 in primary rat hippocampal cultures reduces dendritic outgrowth and arborization, as well as spine maturation. Moreover, knockdown of zDHHC15 reduces palmitoylation of PSD-95 and its trafficking into dendrites, resulting in an overall decrease in the density of excitatory synapses being formed onto mutant cells.
Predictors of age at first child’s birth and contraceptive use among men in Uganda
Authors: Nsobya Henry , Kabagenyi Allen , Rusatira Jean Christophe 
Published: June 2019

Background: Globally, research on age at first child’s birth among men has been neglected especially in Africa. Consequently, little is known about its impact on male involvement in reproductive health. This paper examined the socio-demographic, economic and proximate predictors of age at first child’s birth among men aged 15-54 years in Uganda. Methods: We used the 2016 Uganda Demographic and Health Survey (UDHS) on a sample of 3,206 men aged 15-54 years who had a biological child. The outcome variable was age at first childbirth categorized as: below 17, 18-24 and 25 years and above (25+). Analysis was done using descriptive statistics, un-adjusted and adjusted multinomial regressions with significance level at 95%. Results: Median age at first child’s birth was 22 years (IQR = 20-25). The majority of men (62.4%) had fatherhood onset between 18 and 24 years. Only 5.2% had fatherhood onset at 17 years or earlier, increasing to 32.4% at 25+. Respondents whose first sexual encounter was before 18 years was 44.3% and 92.7% by 24+. Few respondents (44.1%) reported use of any contraceptive methods. Anglican religion (RRR=1.62; CI 1.06 – 2.46) or not having attended school (RRR=2.20; CI 1.02-4.71) were predictors of childbirth onset before 17 years. Age of sex debut at 18 years or higher (RRR= 2.09, CI 1.72 – 2.54) and secondary and above education (RRR = 1.76, CI 1.42-2.18) were predictors of fatherhood onset at 25+. Contraceptive use among men had no association with age at first child’s birth. Conclusion: These findings are important for strategic allocation of resources to curb early onset of fatherhood among adolescent and young men under the age of 25 years. They highlight the need for gender-sensitive interventions targeting men for behavioral change, participation in Sexual and Reproductive Health Rights (SRHR) programming and improved access to services delivery.
Dementia: prevalence and pathophysiology
Authors: Nazarko Linda 
Published: June 2019

An estimated 954 000 people in the UK have dementia. The number of people with dementia is projected to rise to 1.14 million by 2025 and to 2.09 million by 2051, as a result of population ageing ( Prince et al, 2014 ).This article, the first in a series, explains about the different types of diseases that can lead to dementia symptoms and our knowledge regarding the development of dementia symptoms.
Salafismus / salafiyya als historische Reformbewegung und ihr Einfluss auf islamische Strömungen der Gegenwart
Authors: Sander Amrei 
Published: June 2019

Abstract
Initially Salafism/salafiyya was an Islamic reform movement that developed in contrast to the tradition of law schools and to Sufism. It was not only fed by different sources, but its contents were also adopted and appropriated by different Islamic movements of the present. This article intends to sketch the historical development and shed light on the multi-faceted movements that adopted basic contents from the salafiyya.
When Lovers Recount their Own Stories: Assimilating Text and Image Units in the Prologue of the Roman de la Poire, MS Paris BnF 2186
Authors: Doggett Laine E. 
Published: June 2019

The prologue of the Roman de la Poire includes speeches from the God of Love, the Goddess Fortune, the poet/narrator of the work and several protagonists from twelfth-century texts. MS Paris BnF 2186 includes nine full-page illuminations (very rare in romance) in the prologue that accompany the speeches, forming units of text and image. This article analyzes the speeches by Cligés, Tristan, and Pyramus with their accompanying illuminations. In the speeches, the lovers narrate their own stories (which they did not in the earlier versions), changing them so as to offer a new and substantially different version of a central episode from their narrative that emphasizes how lovers manage appearances, shape perceptions and respond to various obstacles to love. Comparisons between the Poire speeches and the twelfth-century texts reveal the divergences and their import for the Poire narrator. The illuminator’s paintings carefully follow the details in the speeches and, through the power of visual representation, fix in the memory of an observer the lovers’ responses to barriers to love. The images and texts work synergistically and have the potential to encourage any lover, including the romance protagonist, who expresses uncertainty and hesitation throughout the text due to fear of slanderers. The Poire points out the importance of memory, and the text and image units of the prologue of MS 2186 establish that importance from the first pages a reader encounters.
Continuity results for parametric nonlinear singular Dirichlet problems
Authors: Bai Yunru , Motreanu Dumitru , Zeng Shengda 
Published: June 2019

AbstractIn this paper we study from a qualitative point of view the nonlinear singular Dirichlet problem depending on a parameterλ> 0 that was considered in [32]. Denoting bySλthe set of positive solutions of the problem corresponding to the parameterλ, we establish the following essential properties ofSλ:there exists a smallest element$\begin{array}{} u_\lambda^* \end{array}$inSλ, and the mappingλ↦$\begin{array}{} u_\lambda^* \end{array}$is (strictly) increasing and left continuous;the set-valued mappingλ↦Sλis sequentially continuous.
Comparison results for nonlinear divergence structure elliptic PDE’s
Authors: Liu Yichen , Marras Monica , Porru Giovanni 
Published: June 2019

AbstractFirst we prove a comparison result for a nonlinear divergence structure elliptic partial differential equation. Next we find an estimate of the solution of a boundary value problem in a domainΩin terms of the solution of a related symmetric boundary value problem in a ballBhaving the same measure asΩ. For p-Laplace equations, the corresponding result is due to Giorgio Talenti. In a special (radial) case we also prove a reverse comparison result.
Aristotle on the Good of Reproduction
Authors: Gabbe Myrna 
Published: June 2019

AbstractThis paper discusses Aristotle’s theory of reproduction: specifically, the good that he thinks organisms attain by reproducing. The aim of this paper is to refute the widespread theory that Aristotle believes plants and animals reproduce for the sake of attenuated immortality. This interpretive claim plays an important role in supporting one leading interpretation of Aristotle’s teleology: the theory that Aristotelian nature is teleologically oriented with a view solely to what benefits individual organisms, and what benefits the organism is its survival and well–being. This paper challenges the theories that Aristotle takes plants and animals to reproduce for the sake of attenuated immortality, and that he believes survival to be the most basic of goods. It is argued that Aristotle believes reproduction is detrimental to organisms’ health and longevity but nonetheless is central to plant and animal flourishing. It is claimed that, to explain the fundamentality of the reproductive soul function, Aristotle appeals to the eternal and divine.
Promêtheiaas Rational Agency in Plato
Authors: Moore Christopher 
Published: June 2019

AbstractThe Greeks knew a virtue term that represented the ability to determine which norms deserved commitment, a virtue term usually misunderstood as “prediction of likely outcomes” or “being hesitant”:promêtheia. Plato’s uses of this term, almost completely ignored by scholarship, show a sensitivity to the prerequisites for the capacity for rational agency. We must add this virtue term to the usual suspects related to acting as a rational agent:sôphrosunê, dikaiosunê, phrônesis, andsophia.Promêtheiastands out for its importance in times of ignorance of the future.
Die Pest und die Juden - Mythen, Fakten, Topoi
Authors: Bergdolt Klaus 
Published: June 2019

Abstract
This paper explores the relation between the »Black Death« and the persecutions of Jews in the mid-14th century. At first glance, it may come as a surprise that pogroms never took place during an outbreak (as some black legends claim). They were a phenomenon which occurred, typically, before or (seldom) after a plague. When everyone had to reckon with the deadly danger, the charge of well-poisoning, which had a long and fatal tradition, moved to the centre again, accompanied by other incriminations of Jews. Having been of more theoretical (or magic) importance before then, the terrible accusation now seemed to be justified more than ever by the medical theory that poisoned water could cause »miasmata«. The general anxiety, described excellently by Petrarch and other contemporaries, provided an ideal playground for fanatics and zealots who tried to convince people of the validity of such assumptions. It is therefore no wonder that the number of pogroms increased dramatically in 1348/49. They were promoted by the tactics of the emperor who sold his profitable role as a »protector of the Jews« increasingly to the »Imperial Free Cities«. In many towns the Black Death was preceded (or sometimes followed) by anti-Jewish massacres that were instigated by anti-Jewish writings and pamphlets. Only a general crisis of mentality and widespread moral decadence made this possible. The solid financial interests of certain groups of society seem also to have played an important role. Nevertheless, we have to admit that these medieval persecutions have left many questions open - to this day.
Homosexualität, Krankheit und Judentum
Authors: Mildenberger Florian G. 
Published: June 2019

Abstract
Twenty years ago, »homosexuality« was only disputed by Rabbis and their scholars, but today LGBT-people are part of daily Jewish life, even in some orthodox communities. Despite the fact that modern Zionism and the sexual reform movement were founded at almost the same time, the two parties were, for many decades, never in accordance. Apparently neither male nor female »sexual in-betweens« fitted into a modern Zionistic culture or orthodox communities. This changed in 1980s due to HIV/AIDS and the success of sexual reform movements in the Western world. Today, the difference between rich and poor seems to be much more important than the question of hetero- or homosexuality.
Problemreduzierungsansätze für die Produktionsplanung unter Verwendung von Auslastungsfunktionen
Authors: Kacar N. Baris , Mönch Lars , Uzsoy Reha 
Published: June 2019

Zusammenfassung
Eine Schwäche vieler linearer Optimierungsansätze für die Produktionsplanung besteht darin, dass sie nicht in der Lage sind, den nichtlinearen Zusammenhang zwischen Umlaufbestand und Durchlaufzeit korrekt abzubilden. Der Umlaufbestand wird dabei durch die auf Bearbeitung wartenden bzw. sich in Bearbeitung befindlichen Jobs gebildet. Nichtlineare Auslastungsfunktionen modellieren diesen Zusammenhang und haben sich als vielversprechend für die Entwicklung effektiver Formulierungen erwiesen. Die Verwendung von Auslastungsfunktionen führt aber zu viel größeren Modellen als für konventionelle Produktionsplanungsformulierungen mit festen Durchlaufzeiten. Außerdem ist erheblicher Aufwand erforderlich, um die Auslastungsfunktionen zu ermitteln. Dieser Artikel untersucht die Leistungsfähigkeit von reduzierten Modellen, bei denen lediglich eine Teilmenge der potentiell kritischen Maschinengruppen durch Auslastungsfunktionen repräsentiert wird, in Bezug auf Kosten und Gewinn. Simulationsexperimente für ein Modell einer großen Halbleiterfabrik zeigen, dass sogar dann reduzierte Modelle wesentlich weniger leistungsfähig sind als Modelle, in denen für alle Maschinengruppen Auslastungsfunktionen verwendet werden, wenn 75 % des Umlaufbestands an Maschinengruppen mit Auslastungsfunktionen anfallen. Diese Ergebnisse belegen, dass die Interaktionen zwischen den Maschinengruppen komplex sind und Modelle, die nur eine eingeschränkte Anzahl von Auslastungsfunktionen verwenden, zu einer falschen Einschätzung der Leistungsfähigkeit des Produktionssystems führen können. Das beobachtete Verhalten wird durch Analyse der Dualvariablen, die zu den Maschinengruppen gehören, erklärt.
Effiziente Initialisierung von Steuerungsparametern für Cyber-Physische Produktionssysteme via Multi-Ebenen-Optimierung
Authors: Zou Minjie , Ocker Felix , Huang Edward , Chen Chun-Hung , Vogel-Heuser Birgit 
Published: June 2019

Zusammenfassung
An moderne Cyber-Physische Produktionssysteme werden hohe Anforderungen hinsichtlich Flexibilität und Effizienz gestellt. Flexibilität wird zum Teil bereits durch moderne Steuerungssoftware unterstützt, wobei die initialen Steuerungsparameter bisher typischerweise ad-hoc festgelegt werden. Dieser Beitrag stellt einen Ansatz zur Optimierung der initialen Steuerungsparameter vor, der mehrere Simulationsmodelle verschiedener Genauigkeit mittels ordinaler Transformation kombiniert. Die Anwendbarkeit des Ansatzes wird anhand eines Labordemonstrators für Produktionssysteme gezeigt.
Echtzeitfähige energiereduzierte Pfadplanung für Mobile Roboter
Authors: Mitschke Marcel , Uchiyama Naoki , Sawodny Oliver 
Published: June 2019

Zusammenfassung
Für Aufgaben wie dem Reinigen von Außenanlagen oder Rasenmähen benötigen mobile Roboter effiziente Algorithmen zur Lösung des Coverage Path Planning (CPP) Problems. Da stetig variierende Umgebungsbedingungen auf CPP-Probleme mit hoher Komplexität führen, wird häufig auf echtzeitfähige heuristische Ansätze mit Vorgaben an die maximale Rechenzeit ausgewichen. Darüber hinaus ist ein möglichst energieeffizienter Pfad erstrebenswert, da die Batteriekapazität von mobilen Robotern begrenzt ist. Diese Veröffentlichung stellt zwei CPP-Algorithmen vor, die den Energieverbrauch eines mobilen Roboters mit und ohne Kenntnis der Umgebung berücksichtigen. Der Energieverbrauch, die benötigte Fahrtzeit, die Pfadlänge und die Rechenzeit der vorgestellten Algorithmen werden simulativ mit zwei existierenden Methoden verglichen.