bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combination Approach for Detecting Different Types of Alterations in Circulating Tumor DNA in Leiomyosarcoma
Authors: Przybyl Joanna , Chabon Jacob J. , Spans Lien , Ganjoo Kristen N. , Vennam Sujay , Newman Aaron M. , Forgó Erna , Varma Sushama , Zhu Shirley , Debiec-Rychter Maria , Alizadeh Ash A. , Diehn Maximilian , van de Rijn Matt 
Published: February 2018

Abstract
Purpose: The clinical utility of circulating tumor DNA (ctDNA) monitoring has been shown in tumors that harbor highly recurrent mutations. Leiomyosarcoma represents a type of tumor with a wide spectrum of heterogeneous genomic abnormalities; thus, targeting hotspot mutations or a narrow genomic region for ctDNA detection may not be practical. Here, we demonstrate a combinatorial approach that integrates different sequencing protocols for the orthogonal detection of single-nucleotide variants (SNV), small indels, and copy-number alterations (CNA) in ctDNA.
Experimental Design: We employed Cancer Personalized Profiling by deep Sequencing (CAPP-Seq) for the analysis of SNVs and indels, together with a genome-wide interrogation of CNAs by Genome Representation Profiling (GRP). We profiled 28 longitudinal plasma samples and 25 tumor specimens from 7 patients with leiomyosarcoma.
Results: We detected ctDNA in 6 of 7 of these patients with &gt;98% specificity for mutant allele fractions down to a level of 0.01%. We show that results from CAPP-Seq and GRP are highly concordant, and the combination of these methods allows for more comprehensive monitoring of ctDNA by profiling a wide spectrum of tumor-specific markers. By analyzing multiple tumor specimens in individual patients obtained from different sites and at different times during treatment, we observed clonal evolution of these tumors that was reflected by ctDNA profiles.
Conclusions: Our strategy allows for the comprehensive monitoring of a broad spectrum of tumor-specific markers in plasma. Our approach may be clinically useful not only in leiomyosarcoma but also in other tumor types that lack recurrent genomic alterations. Clin Cancer Res; 24(11); 2688–99. ©2018 AACR.
Targeting Cytokine Therapy to the Pancreatic Tumor Microenvironment Using PD-L1–Specific VHHs
Authors: Dougan Michael , Ingram Jessica R. , Jeong Hee-Jin , Mosaheb Munir M. , Bruck Patrick T. , Ali Lestat , Pishesha Novalia , Blomberg Olga , Tyler Paul M. , Servos Mariah M. , Rashidian Mohammad , Nguyen Quang-De , von Andrian Ulrich H. , Ploegh Hidde L. , Dougan Stephanie K. 
Published: February 2018

Abstract
Cytokine-based therapies for cancer have not achieved widespread clinical success because of inherent toxicities. Treatment for pancreatic cancer is limited by the dense stroma that surrounds tumors and by an immunosuppressive tumor microenvironment. To overcome these barriers, we developed constructs of single-domain antibodies (VHHs) against PD-L1 fused with IL-2 and IFNγ. Targeting cytokine delivery in this manner reduced pancreatic tumor burden by 50%, whereas cytokines fused to an irrelevant VHH, or blockade of PD-L1 alone, showed little effect. Targeted delivery of IL-2 increased the number of intratumoral CD8+ T cells, whereas IFNγ reduced the number of CD11b+ cells and skewed intratumoral macrophages toward the display of M1-like characteristics. Imaging of fluorescent VHH–IFNγ constructs, as well as transcriptional profiling, demonstrated targeting of IFNγ to the tumor microenvironment. Many tumors and tumor-infiltrating myeloid cells express PD-L1, rendering them potentially susceptible to this form of targeted immunotherapy. Cancer Immunol Res; 6(4); 389–401. ©2018 AACR.
Vulnerability to Infarction During Cerebral Ischemia in Migraine Sufferers
Authors: Pezzini Alessandro , Busto Giorgio , Zedde Marialuisa , Gamba Massimo , Zini Andrea , Poli Loris , Caria Filomena , De Giuli Valeria , Simone Anna Maria , Pascarella Rosario , Padovani Alessandro , Padroni Marina , Gasparotti Roberto , Colagrande Stefano , Fainardi Enrico 
Published: February 2018

Background and Purpose—
Cerebral hyperexcitability in migraine experiencers might sensitize brain tissue to ischemia. We investigated whether a personal history of migraine is associated with vulnerability to brain ischemia in humans.

Methods—
Multicenter cohort study of patients with acute ischemic stroke who underwent a brain computed tomography perfusion and were scheduled to undergo reperfusion therapy. In a case–control design, we compared the proportion of subjects with no-mismatch, the volume of penumbra salvaged, as well as the final infarct size in a group of patients with migraine and a group of patients with no history of migraine.

Results—

We included 61 patients with migraine (34 [55.7%] men; mean age, 52.2±15.1 years; migraine without aura/migraine with aura, 44/17) and 61 patients with no history of migraine. The proportion of no-mismatch among migraineurs was significantly higher than among nonmigraineurs (17 [27.9%] versus 7 [11.5%];
P
=0.039) and was more prominent among patients with migraine with aura (6 [35.3%];
P
=0.030) while it was nonsignificantly increased in patients with migraine without aura (11 [25.0%];
P
=0.114). Migraine, especially migraine with aura, was independently associated with a no-mismatch pattern (odds ratio, 2.65; 95% CI, 0.95–7.41 for migraine; odds ratio, 5.54; 95% CI, 1.28–23.99 for migraine with aura), and there was a linear decrease of the proportion of patients with migraine with aura with increasing quartiles of mismatch volumes. Patients with migraine with aura had also smaller volumes of salvaged penumbra (9.8±41.2 mL) compared with patients with migraine without aura (36.4±54.1 mL) and patients with no migraine (45.1±55.0 mL;
P
=0.056). Conversely, there was no difference in final infarct size among the 3 migraine subgroups (
P
=0.312).

Conclusions—
Migraine is likely to increase individual vulnerability to ischemic stroke during the process of acute brain ischemia and might represent, therefore, a potential new therapeutic target against occurrence and progression of the ischemic damage.
Samuel Palmer, John Martin, and John Sell Cotman
Authors: Stuart Kathleen 
Published: February 2018

Abstract
This article considers how a viewer identifies spiritual meaning in landscape images of the Romantic era as well as the role of artists’ statements about their work in a viewer’s interpretive process. It examines landscapes by Samuel Palmer and John Martin, two early nineteenth-century British artists known for the spiritual content of their work, and the connection between the work and their published statements about it. The article also considers the “secular” landscapes by their contemporary John Sell Cotman for the work’s possible spiritual meaning despite the absence of published comments by the artist on the subject.
Frederic Shields’s Chapel of the Ascension
Authors: Frederick Margaretta S. 
Published: February 2018

Abstract
In 1889 the Pre-Raphaelite artist Frederic Shields (1833–1911) received a commission to paint the walls of a chapel in London. The patron, Emelia Gurney (1823–1896), was a devout Christian who envisaged a non-denominational place of worship and reflection, a place of refuge from the accelerated pace of the industrial age. The building, located just off Hyde Park in the Bayswater section of London, was designed by the architect Herbert Horne (1864–1916) and was based on Italian quattrocento ecclesiastical design. The interior walls were covered in a rich iconographical program conceived jointly by patron and artist. The pictorial narrative, painted in high Renaissance style, emphasized the theme of salvation and can be understood as a direct response to the fragmentation of religious practice and belief taking place in Britain at the time. This article is an investigation of the Chapel’s painted pedagogy. Completed in 1910, the building was bombed during the Blitz and is no longer standing.
Editors’ Introduction
Authors: Romaine James , Hostetter Smith Rachel 
Published: February 2018

Abstract
Framing the eleven essays in this special double issue, this introduction opens a discussion, continued throughout the issue, on the pervasive impulse toward and elastic meaning of the ideal of paradise which was of particular interest to nineteenth-century British and American artists. It describes the arc of the issue, which is organized into three parts: on British art, American art, and architectural projects. It is bracketed by an essay that looks back to the influence of Renaissance Florence on nineteenth-century British and Americans and a postscript on paradisiacal themes in the work of two contemporary British and American artists. The genesis of this special issue is the 2016 symposium Picturing Paradise in Nineteenth Century British and American Art: Past, Lost, Regained organized by the Association of Scholars of Christianity in the History of Art.
Larval developmental temperature and ambient temperature affect copulation duration in a seed beetle
Authors: Vasudeva R. , Deeming D.C. , Eady P.E. 
Published: February 2018

Abstract
The effects of temperature on cellular, systemic and whole-organism processes can be short-term, acting within seconds or minutes of a temperature change, or long-term, acting across ontogenetic stages to affect an organism’s morphology, physiology and behavioural phenotype. Here we examine the effect of larval development temperature on adult copulatory behaviour in the bruchid beetle, Callosobruchus maculatus. As predicted by temperature’s kinetic effects, copulation duration was longest at the lowest ambient temperature. However, where ambient temperature was fixed and developmental temperature experimentally varied, males reared at the highest temperature were least likely to engage in copulation, whilst those reared at the lowest temperature copulated for longer. Previous research has shown males reared at cooler temperatures inseminate fewer sperm. Thus, in this species longer copulations are associated with reduced sperm transfer. We argue that knowledge of preceding ontogenetic conditions will help to elucidate the causes of variation in copulatory behaviour.
Paurodontella gilanica n. sp. (Nematoda: Sphaerularioidea) from Iran
Authors: Yaghoubi Ali , Pourjam Ebrahim , Pedram Majid 
Published: February 2018

Summary
Paurodontella gilanica n. sp. is described and illustrated based on morphological, morphometric and molecular characters. The new species is characterised by its small body size, four lines in the lateral field, weak stylet with minute asymmetrical knobs, female reproductive system lacking a diverticulum but with small post-vulval uterine sac, elongate conoid tail with pointed, sometimes filiform, tip, males common with small spicules and cloacal bursa not reaching tail tip. Morphological differences between the new species and seven known species of the genus, namely P. asymmetrica, P. auriculata, P. balochistanica, P. minuta, P. myceliophaga, P. parapitica and P. persica, are discussed. The new species is also compared with four known species of Paurodontus having four lines in the lateral field. Using a 1123 nt long partial 18S rDNA sequence of the new species to reconstruct the phylogenetic relationships revealed that it formed a clade with members of the Sphaerulariidae and Paurodontidae. Using a 746 nt long partial sequence of the 28S rDNA D2-D3 segment revealed that P. gilanica n. sp. formed a clade with Abursanema iranicum in both Bayesian inference (BI) and maximum likelihood (ML) analyses with 0.99 Bayesian posterior probability (BPP) and 89% bootstrap support value (BS). The morphological affinities of Paurodontella and Paurodontus are discussed.
Geometric analysis of intrusive growth of wood fibres in Robinia pseudoacacia
Authors: Wilczek Anna B. , Iqbal Muhammad , Wloch Wieslaw , Klisz Marcin 
Published: February 2018

ABSTRACT
All cell types of the secondary xylem arise from the meristematic cells (initials) of the vascular cambium and grow under mechanical constraints emerging from the circular-symmetrical geometry that characterises many tree trunks. The course of intrusive growth of cambial initials has been elucidated, but is yet to be described in the case of xylem fibres. This study explains the geometry of intrusive growth of the secondary xylem fibres in the trunk of Robinia pseudoacacia. Long series of serial semi-thin sections of the vascular cambium and the differentiating secondary xylem were analysed. Since fibres grow in close vicinity to expanding cells of the derivatives of the vascular cambium, we assumed that they have similar growth conditions. Dealing with the cylindrical tissue of the vascular cambium in a previous study, we used a circularly symmetrical equation for describing the growth mechanism of cambial initials. Like the cambial initials, some of the cambial derivatives differentiating into the various cell types composing the secondary xylem also exhibit intrusive growth between the tangential walls of adjacent cells. As seen in cross sections of the cambium, intrusively growing initials form slanted walls by a gradual transformation of tangential (periclinal) walls into radial (anticlinal) walls. Similarly, the intrusive growth of xylem fibres manifests initially as slants, which are formed due to axial growth of the growing cell tips along the tangential walls of adjacent cells. During this process, the tangential walls of adjacent cells are partly separated and dislocated from the tangential plane. The final shape of xylem fibres, or that of vessel elements and axial parenchyma cells, depends upon the ratio of their intrusive versus symplastic growths in the axial, circumferential and radial directions.
Ice nucleation in stems of trees and shrubs with different frost resistance
Authors: Schott Rena T. , Roth-Nebelsick Anita 
Published: February 2018

Abstract
In this study, the ice nucleation activity (INA) and ice nucleation temperature (INT) as well as extracellular ice formation within the bark were determined for three woody species with different degrees of frost resistance, Betula nana, Betula albosinensis and Castanea sativa. Current-year stems and at least 2-year old stems of B. nana and C. sativa as well as current-year stems of B. albosinensis were compared, during summer (non-acclimated state) and winter (acclimated state), to evaluate possible ontogenetic and seasonal differences. Acclimated plant parts of the selected species revealed nearly similar results, with an INT from -7.52 to -8.43°C. The current-year stems of B. nana had a somewhat higher INT than the older stems. Microscopic analysis showed that extra-cellular ice formation occurred in the intercellular spaces within the bark of stems of B. nana, B. albosinensis and C. sativa. Size of the intercellular spaces of the bark were species-specific, and B. nana showed the largest intercellular space volume. While freezing behavior and extracellular ice formation thus followed principally the same pattern in all considered species, B. nana is obviously capable of dealing with large masses of extracellular ice which accumulate over extended periods of frost, making B. nana capable of protecting living tissue in colder regions from freezing damage.
Transnational Organization, Transnational Law and the Ambiguity of Interpol in a World Ruled with Law
Authors: Sheptycki James 
Published: February 2018

Abstract
Using the practical empirical example of the Interpol Organization, the paper explores the relationship between transnational organization and transnational law. Pace Jessup’s pioneering work in 1956, the central questions surrounding the notion of transnational law have involved understanding the use of legal tools in an administrative grey area of global governance across a range of legal institutions. This essay demonstrates how Interpol constituted as itself a formal ‘Intergovernmental Organization’ with its own self-governing structure and explores the use of one of its most powerful legal tools: the Red Notice. As a formally constituted igo with transnational reach and legally subject to its own constituted governance processes, Interpol is an example of what Neil Walker calls ‘constitutionalism beyond the State’. A fortiori, Interpol mobilizes a range of legal tools from transnational public international law and criminal law, as well as those of its own constitutional order, in making up its organization. Following Terence C. Halliday and Gregory Shaffer, and based on this empirical case study, the essay argues that Interpol is an important constituent element in the broader ‘transnational legal order’ of global policing. The challenge for socio-legal scholarship is to reveal how the transnational legal order of which Interpol is a part, is shaped by a variety of actors using different kinds of legal instruments because the institutional patterns thereby established have consequences for future developments. The transnational legal order of global policing is a synecdoche of global governance more generally and the specific case of Interpol provides the basis of some general claims about how to understand the concept of law under transnational conditions. The essay argues that Interpol is but a small constituent element of an evolving global system of rule with law. Rule with law emphasizes that in all practical circumstances legal tools are in the hands of knowing social actors. Understood this way, law is practical politics undertaken by means of legal tools. Interpol is but one element of a vast transnational legal order that has no democratic basis and which needs to be progressively uncovered through piecemeal empirical case studies. Read against the backdrop of broad socio-legal theory, such case studies offer critical insights concerning contemporary transnational legal ordering.
Opioid Prescribing Patterns among Otolaryngologists
Authors: Schwartz Marissa A. , Naples James G. , Kuo Chia‐Ling , Falcone Todd E. 
Published: February 2018

ObjectivesTo evaluate national trends in opioid prescribing patterns by otolaryngologists for postoperative pain control after common otolaryngologic procedures.Study DesignCross‐sectional; survey.Subjects and MethodsA survey to determine opioid prescribing patterns for the treatment of postoperative pain following common otolaryngologic procedures was distributed to all members of the American Academy of Otolaryngology–Head and Neck Surgery.ResultsThe most common pain medication prescribed for adults postoperatively was hydrocodone‐acetaminophen (73%), followed by oxycodone‐acetaminophen (39%). The most common pain medication prescribed postoperatively for children was acetaminophen (67%), followed by nonsteroidal anti‐inflammatory drugs (65%). Overall, there was a wide variation in quantity of opioids prescribed for each surgery, ranging from 0 to more than 60 doses. Mean opioid prescriptions were greatest for tonsillectomy (37 tablets) and least for direct laryngoscopy (5.3 tablets).ConclusionThis study identifies nationwide variations in opioid prescribing patterns among otolaryngologists. While otolaryngology is a relatively small specialty, we still have an obligation to work with all physicians to help combat the current opioid epidemic. By evaluating nationwide postoperative pain regimens, we are moving closer toward understanding how to reduce the opioid burden.
Recruiting and Retaining Patient–Caregiver–Nurse Triads for Qualitative Hospice Cancer Pain Research
Authors: Ehrlich Olga , Walker Rachel K. 
Published: February 2018

Background: Qualitative pain research for hospice patients with cancer and their caregivers involves recruiting and retaining participants with multiple vulnerabilities and ethical and logistical challenges. These have been reported for studies of individuals or dyads. However, there are no reports of the related challenges and outcomes where the sampled population was a hospice triad. Objectives: Qualitative research about pain management for home hospice patients with cancer contributes rich descriptive data and such studies are critical to improving cancer pain outcomes. We describe the ethical and pragmatic challenges we faced in a study of the hospice caring triad, operationalized as the patient, family caregiver, and nurse; how our study design anticipated them; and related outcomes. Results: We found that having an established relationship with the hospice agency at which we recruited participants, clearly identifying potential participants at the onset of hospice care, practice using a recruitment script, patient recruitment of caregivers, establishing rapport, and participants determining when interviews should end helped us recruit and retain our sample. We were unable to accrue our anticipated triad sample, partially because of nurse gatekeeping and the condition at admission of patient participants who enrolled but had physical decline or died prior to written consent. Conclusions: Although researchers will always face challenges to enrolling individuals and groups in cancer pain studies, with careful study design, recruitment, and retention planning and research team-participant engagement, it is possible to gather a robust corpus of qualitative data.
Neutrophils provide cellular communication between ileum and mesenteric lymph nodes at graft-versus-host disease onset
Authors: Hülsdünker Jan , Ottmüller Katja J. , Neeff Hannes P. , Koyama Motoko , Gao Zhan , Thomas Oliver S. , Follo Marie , Al-Ahmad Ali , Prinz Gabriele , Duquesne Sandra , Dierbach Heide , Kirschnek Susanne , Lämmermann Tim , Blaser Martin J. , Fife Brian T. , Blazar Bruce R. , Beilhack Andreas , Hill Geoffrey R. , Häcker Georg , Zeiser Robert 
Published: February 2018

Key Points
Neutrophils migrate to the ileum after conditioning and contribute to GVHD. JAK1/JAK2 inhibition reduces neutrophil influx and MHC-II expression in the mesenteric lymph node.
Glutaminolysis is a metabolic dependency in FLT3ITD acute myeloid leukemia unmasked by FLT3 tyrosine kinase inhibition
Authors: Gallipoli Paolo , Giotopoulos George , Tzelepis Konstantinos , Costa Ana S. H. , Vohra Shabana , Medina-Perez Paula , Basheer Faisal , Marando Ludovica , Di Lisio Lorena , Dias Joao M. L. , Yun Haiyang , Sasca Daniel , Horton Sarah J. , Vassiliou George , Frezza Christian , Huntly Brian J. P. 
Published: February 2018

Key PointsFLT3ITD TK inhibition impairs glycolysis and glucose utilization without equally affecting glutamine metabolism. Combined targeting of FLT3 TK activity and glutamine metabolism decreases FLT3ITD mutant cells leukemogenic potential in vitro and in vivo.
Improving Discrete Data Capture in Synoptic Reports With Optional Free-Text Modifiers
Authors: Renshaw Andrew A. , Gould Edwin W. 
Published: February 2018

Purpose Upfront, discrete data capture in synoptic reporting fails when pathologists choose a response not associated with discrete data. We sought to determine the factors associated with this event. Methods The results of all “Other” entries in four common tumor sites in synoptic reports were reviewed. Results “Other” entries occurred in 329 of 13,421 questions (2.5%). In 306 of these 329 questions (93.0%), the pathologist appeared to choose this response because they wished to add additional information to an already existing response that was associated with discrete data capture. As a result, the addition of a free-text modifiers to existing responses would allow pathologist to add this additional information while still selecting a response associated with discrete data capture, significantly improving the total discrete data capture (13,092 of 13,421 questions [97.5%] v 13,398 of 13,421 questions [99.8%]; P < .001). Conclusion The addition of free-text modifiers to structured responses in synoptic reports could significantly improve the discrete data capture rate.