bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of ALK, ROS1, and RET Fusions by a Multiplexed mRNA-Based Assay in Formalin-Fixed, Paraffin-Embedded Samples from Advanced Non–Small-Cell Lung Cancer Patients
Authors: Reguart Noemí , Teixidó Cristina , Giménez-Capitán Ana , Paré Laia , Galván Patricia , Viteri Santiago , Rodríguez Sonia , Peg Vicente , Aldeguer Erika , Viñolas Nuria , Remon Jordi , Karachaliou Niki , Conde Esther , Lopez-Rios Fernando , Nadal Ernest , Merkelbach-Bruse Sabine , Büttner Reinhard , Rosell Rafael , Molina-Vila Miguel A , Prat Aleix 
Published: January 2017

Abstract

BACKGROUND
Anaplastic lymphoma receptor tyrosine kinase (ALK), ROS proto-oncogene 1, receptor tyrosine kinase (ROS1), and ret proto-oncogene (RET) fusions are present in 5%–7% of patients with advanced non–small-cell lung cancer (NSCLC); their accurate identification is critical to guide targeted therapies. FISH and immunohistochemistry (IHC) are considered the gold standards to determine gene fusions, but they have limitations. The nCounter platform is a potentially useful genomic tool for multiplexed detection of gene fusions, but has not been validated in the clinical setting.

METHODS
Formalin-fixed, paraffin embedded (FFPE) samples from 108 patients with advanced NSCLC were analyzed with an nCounter-based assay and the results compared with FISH, IHC, and reverse transcription PCR (RT-PCR). Data on response to fusion kinase inhibitors was retrospectively collected in a subset of 29 patients.

RESULTS
Of 108 FFPE samples, 98 were successfully analyzed by nCounter (91%), which identified 55 fusion-positive cases (32 ALK, 21 ROS1, and 2 RET). nCounter results were highly concordant with IHC for ALK (98.5%, CI = 91.8–99.7), while 11 discrepancies were found compared with FISH (87.5% concordance, CI = 79.0–92.9). For ROS1, nCounter showed similar agreement with IHC and FISH (87.2% and 85.9%), but a substantial number of samples were positive only by 1 or 2 techniques. Of the 25 patients deriving clinical benefit from fusion kinase inhibitors, 24 were positive by nCounter and 22 by FISH.

CONCLUSIONS
nCounter compares favorably with IHC and FISH and can be used for identifying patients with advanced NSCLC positive for ALK/ROS1/RET fusion genes.
Perbedaan Myocardial Performance Index-Tissue Doplpler Imaging Ventrikel Kanan pada Bayi Kurang Bulan dan Bayi Cukup Bulan
Authors: Nopita Ineu , Rachmadi Dedi , Rahayuningsih Sri Endah 
Published: January 2017

Latar belakang.Bayi kurang bulan merupakan masalah di negara maju maupun negara berkembang. Pada bayi kurang bulan tahanan vaskular paru masih tinggi, sehingga tekanan di ventrikel kanan tinggi. Pengukuran fungsi ventrikel kanan sulit dilakukan dengan ekokardiografi standar karena bentuk geometri ventrikel kanan yang berbentuk “bulan sabit” dan trabekuler yang kasar.Myocardial performance index tissue doppler imaging (MPI-TDI) adalah cara pengukuran fungsi ventrikel kanan yang baru dikembangkan, merupakan penilaian fungsi ventrikel kanan pada fetus, anak, dan dewasa dengan berbagai penyakit jantung. Tujuan.Menilai apakah MPI-TDI pada bayi cukup bulan lebih tinggi dibandingkan dengan kurang bulan dan bagaimana korelasi antara MPI-TDI dan usia kehamilan.Metode.Penelitian dilakukan terhadap 36 bayi (17 bayi kurang bulan dan 19 bayi cukup bulan), berusia kehamilan 33–42 minggu, yang menjalani pemeriksaan MPI-TDI dengan menggunakan ekokardiografi, di Instalasi Pelayanan Jantung RS Dr. Hasan Sadikin periode Juli–Oktober 2010 dengan rancangan potong lintang. Analisis statistik yang digunakan adalah one wayANOVA untuk menilai perbedaan MPI-TDI bayi cukup bulan dan kurang bulan serta uji korelasi rankSpearman untuk menilai korelasi antara MPI-TDI dan usia kehamilan dengan kemaknaan hasil uji bila didapatkan p<0,05.Hasil.Didapatkan rerata MPI-TDI untuk bayi usia kehamilan <34 minggu adalah 0,31 (0,03), bayi usia kehamilan 34–36 minggu 0,32 (0,03) dan bayi usia kehamilan >37 minggu adalah 0,30 (0,03) (p=0,03). Nilai korelasi antara MPI-TDI dan usia kehamilan adalah (0,24) dengan nilai p=0,378. Kesimpulan.Didapatkan perbedaan MPI-TDI ventrikel kanan antara bayi kurang bulan dan cukup bulan. Tidak ada korelasi antara MPI TDI dan usia kehamilan.
Ewing's Sarcoma Family Tumors pada ANak [Keganasan Kelompok Sarkoma Ewing] di RS Cipto Mangunkusumo
Authors: Sari Teny Tjitra , Gatot Djajadiman , Windiastuti Endang 
Published: January 2017

Latar belakang.Terapi multimodalitas pada Ewing’s sarcoma family tumors(keganasan kelompok sarkoma Ewing) telah banyak meningkatkan keberhasilan terapi. Guna menilai keberhasilan terapi diperlukan data mengenai luaran pasien keganasan kelompok sarkoma Ewing.Tujuan.Mengetahui gambaran klinis dan luaran pasien sarkoma Ewing yang dirawat di Divisi Hematologi Onkologi Departemen Ilmu Kesehatan Anak RS Cipto Mangunkusumo Metode.Studi deskriptif dilakukan pada pasien yang didiagnosis keganasan kelompok sarkoma Ewing di Divisi Hematologi Onkologi Departemen Ilmu Kesehatan Anak RS Cipto Mangunkusumo, pada tahun 2000–2010. Terapi yang diberikan adalah kemoterapi, pembedahan, dan radioterapi. Hasil. Selama periode pengamatan sepuluh tahun dijumpai 26 pasien keganasan kelompok sarkoma Ewing dari seluruh 2112 pasien keganasan anak. Usia berkisar 6 bulan – 13 tahun 1 bulan (median 8 tahun 3 bulan). Lokasi tersering adalah ekstremitas, tulang belakang, dan pelvis. Sebagian besar pasien (16 dari 26 pasien) datang dengan stadium lanjut. Kemoterapi terutama diberikan pada lokasi tumor aksial (12 dari 26 pasien), sedangkan pembedahan yang dilanjutkan kemoterapi dilakukan bila lokasi tumor berada di ekstremitas (4 dari 26 pasien). Pasien meninggal lebih banyak dengan lokasi tumor di aksial (9 pasien) dibanding ekstremitas (3 pasien). Jumlah pasien hidup lebih banyak yang berusia < 10 tahun dibanding umur yang lebih tua (6 berbanding 1). Residif terjadi pada dua pasien dengan jangka waktu 11 bulan.Kesimpulan. Luaran pasien keganasan kelompok sarkoma Ewing masih jauh dari memuaskan. Pasien meninggal lebih banyak daripada pasien hidup, terutama letak tumor di aksial. Sebagian besar pasien datang pada stadium lanjut dan telah mengalami metastasis. Modalitas yang lebih intensif perlu diberikan untuk meningkatkan luaran pasien keganasan kelompok sarkoma Ewing.
Informationsbedarf für automatische IT-Sicherheitsanalysen automatisierungstechnischer Anlagen
Authors: Tebbe Christopher , Glawe Matthias , Niemann Karl-Heinz , Fay Alexander 
Published: January 2017

Zusammenfassung
Für die Durchführung einer IT-Sicherheitsanalyse sind die Informationen über die zu betrachtende Anlage von zentraler
Bedeutung. Neben den Anlageninformationen wird relevantes IT-Sicherheitswissen (z. B. Bedrohungen, Schutzmaßnahmen usw.)
benötigt. Dieses setzt als Grundlage Informationen über die zu analysierende Anlage voraus. In diesem Beitrag werden auf
Basis des IT-sicherheitsrelevanten Wissens die für eine IT-Sicherheitsanalyse benötigten Anlageninformationen
ermittelt. Darauf aufbauend werden mögliche Informationsquellen im Engineering
identifiziert und diskutiert.
Modellsynthese für die Testfallgenerierung sowie
Testdurchführung unter Nutzung von Methoden zur Netzwerkanalyse
Authors: Magnus Stephan , Ruß Tim , Krause Jan , Diedrich Christan 
Published: January 2017

Zusammenfassung
Die automatische
Testdurchführung und die modellbasierte Testgenerierung als Teil der
Testautomatisierung verbessern den Testprozess und letztendlich die
Qualität von Produkten. Der Grund sind die
automatisierte Wiederholbarkeit der Testfälle sowie eine höhere
Testabdeckung. In diesem Beitrag werden zu diesem Zweck
eine anforderungsbasierte Systembeschreibung und eine Modellsynthese zu
einem Spezifikationsmodell dargestellt. Sie haben das
Ziel, eine vorgelagerte Unterstützung und somit eine
Reduzierung der Einstiegshürde für die modellbasierte
Testgenerierung zu ermöglichen. Ebenso wird in
diesem Beitrag eine Methode zur Netzwerkanalyse und
-manipulation aufgezeigt, um die
Testdurchführung mit der Überprüfung des Sollverhaltens von
relevantem Netzwerkverkehr zu automatisieren und zu
verbessern. Dazu wird eine prototypisch implementierte
Toolkette vorgestellt, die von der
Anforderungsbeschreibung bis zum Testen einer Anlage
reicht.
An Introduction to the Analysis and Implementation of Sparse Grid Finite Element Methods
Authors: Russell Stephen , Madden Niall 
Published: January 2017

Abstract
Our goal is to present an elementary approach to the
analysis and programming of sparse grid finite element methods. This
family of schemes can compute accurate solutions to partial
differential equations, but using far fewer degrees of freedom than
their classical counterparts.
After a brief discussion of the
classical Galerkin finite element method with bilinear elements, we
give a short analysis of what is probably the simplest sparse grid
method: the two-scale technique of Lin et
al. [14]. We
then demonstrate how to extend this to a multiscale sparse
grid method which, up to choice of basis, is equivalent to the hierarchical
approach,
as described by, e.g., Bungartz and Griebel [4]. However, by presenting it as
an extension of the
two-scale method, we can give an elementary treatment of its analysis
and implementation.
For each method considered, we provide MATLAB code, and a comparison of accuracy and computational costs.
A Parameter Robust Finite Element Method for Fourth Order Singularly Perturbed Problems
Authors: Xenophontos Christos 
Published: January 2017

Abstract
We consider fourth order singularly perturbed problems in one-dimension and
the approximation of their solution by the h version of the finite element method. In particular, we use piecewise Hermite polynomials of degree

p
≥
3

${p\geq 3}$

defined on an exponentially graded mesh. We show that the
method converges uniformly, with respect to the singular perturbation
parameter, at the optimal rate when the error is measured in both the energy norm
and a stronger, ‘balanced’ norm. Finally, we illustrate our theoretical findings
through numerical computations, including a comparison with another scheme from the literature.
Loose ends in the eradication of Helicobacter pylori infection
Authors: Peixoto Armando , Silva Marco , Gaspar Rui , Morais Rui , Ramalho Rosa , Macedo Guilherme , Santos-Antunes João 
Published: January 2017

Abstract
The eradication of Helicobacter pylori is essential for prevention and treatment of various conditions associated with this infection. However, its effectiveness is limited and influenced by factors linked to the bacteria and the host. In particular, influence of the biotype, smoking, diabetes mellitus, and previous treatment failure in eradication is understudied. Our center proposed to evaluate these aspects in a real life cohort by applying a questionnaire with demographic and lifestyle variables in patients who consecutively underwent urease breath test after the eradication therapy.
Characterization of polymeric shape memory materials
Authors: Wu Xue Lian , Huang Wei Min , Lu Hai Bao , Wang Chang Chun , Cui Hai Po 
Published: January 2017

Abstract
After a short discussion of various shape memory related phenomena and the basic working mechanisms behind the shape memory effect (SME) in polymeric shape memory materials (SMMs), standard techniques and procedures to characterize these types of materials are reviewed in details (including the concerns in the selection of testing methods and parameters). Although the focus of this paper is on the heating-responsive SME, important issues in the chemo-responsive SME are addressed. Furthermore, some other shape memory related phenomena, such as various kinds of temperature memory effect (TME), and multiple-SME etc., and optimization of the shape memory performance of a shape memory polymer (SMP) via tailoring the programming parameters are included.
Modellbasierte Rauschvorhersage für Streifenprojektionssysteme – Ein Werkzeug zur statistischen Analyse von Auswertealgorithmen
Authors: Fischer Marc , Petz Marcus , Tutsch Rainer 
Published: January 2017

Zusammenfassung
In flächenhaft messenden optischen 3D-Messystemen stellt das Rauschen der eingesetzten Kameras den dominierenden
Unsicherheitsbeitrag dar, wenn optisch kooperative Oberflächen unter gut kontrollierten Umgebungsbedingungen gemessen
werden. In der industriellen Praxis wird für diese Art von Messsystemen häufig auf Wiederholungsmessungen verzichtet. Dies
führt im weiteren Verlauf des Messprozesses zu statistisch suboptimalen Ergebnissen, da die wichtige Aussage über die
Qualität der einzelnen Messpunkte verloren geht. In der vorliegenden Arbeit wird gezeigt, wie sich für Messsysteme mit
strukturierter Beleuchtung eine solche Qualitätsaussage auf der Grundlage einer Rauschmodellierung gewinnen lässt. Mit
Hilfe eines Streifenprojektionssystems wird beispielhaft die Leistungsfähigkeit des Ansatzes demonstriert und gezeigt,
dass auf diese Weise für jeden Messpunkt neben der gesuchten geometrischen Information auch eine Schätzung für die aus dem
Kamerarauschen resultierenden stochastischen Abweichungen bestimmt werden kann. Darüber hinaus eignet sich die
dargestellte Methode sehr gut als Werkzeug zur statistischen Analyse von Auswertealgorithmen. Dies wird exemplarisch
anhand zweier verschiedener Triangulationsverfahren demonstriert.
Dopamine Modulates the Functional Organization of the Orbitofrontal Cortex
Authors: Kahnt Thorsten , Tobler Philippe N. 
Published: January 2017

Neuromodulators such as dopamine can alter the intrinsic firing properties of neurons and may thereby change the configuration of larger functional circuits. The primate orbitofrontal cortex (OFC) receives dopaminergic input from midbrain nuclei, but the role of dopamine in the OFC is still unclear. Here we tested the idea that dopaminergic activity changes the pattern of connectivity between the OFC and the rest of the brain and thereby reconfigures functional networks in the OFC. To this end, we combined double-blind, placebo-controlled pharmacology [D2receptor (D2R) antagonist amisulpride] in humans with resting-state functional magnetic resonance imaging and clustering methods. In the placebo group, we replicated previously observed parcellations of the OFC into two and six subregions based on connectivity patterns with the rest of the brain. Most importantly, while the twofold clustering did not differ significantly between groups, blocking D2Rs significantly changed the composition of the sixfold parcellation, suggesting a dopamine-dependent reconfiguration of functional OFC subregions. Moreover, multivariate decoding analyses revealed that amisulpride changed the whole-brain connectivity patterns of individual OFC subregions. In particular, D2R blockade shifted the balance of OFC connectivity from associative areas in the temporal and parietal lobe toward functional connectivity with the frontal cortex. In summary, our results suggest that dopamine alters the composition of functional OFC circuits, possibly indicating a broader role for neuromodulators in the dynamic reconfiguration of functional brain networks.SIGNIFICANCE STATEMENTA key role of any neuromodulator may be the reconfiguration of functional brain circuits. Here we test this idea with regard to dopamine and the organization of functional networks in the orbitofrontal cortex (OFC). We show that blockade of dopamine D2receptors has profound effects on the functional connectivity patterns of the OFC, yielding altered connectivity-based subdivisions of this region. Our results suggest that dopamine changes the connectional configuration of the OFC, possibly leading to transitions between different operating modes that favor either sensory input or recurrent processing in the prefrontal cortex. More generally, our findings support a broader role for neuromodulators in the dynamic reconfiguration of functional brain networks and may have clinical implications for understanding the actions of antipsychotic agents.
Folding, But Not Surface Area Expansion, Is Associated with Cellular Morphological Maturation in the Fetal Cerebral Cortex
Authors: Wang Xiaojie , Studholme Colin , Grigsby Peta L. , Frias Antonio E. , Cuzon Carlson Verginia C. , Kroenke Christopher D. 
Published: January 2017

Altered macroscopic anatomical characteristics of the cerebral cortex have been identified in individuals affected by various neurodevelopmental disorders. However, the cellular developmental mechanisms that give rise to these abnormalities are not understood. Previously, advances in image reconstruction of diffusion magnetic resonance imaging (MRI) have made possible high-resolutionin uteromeasurements of water diffusion anisotropy in the fetal brain. Here, diffusion anisotropy within the developing fetal cerebral cortex is longitudinally characterized in the rhesus macaque, focusing on gestation day (G85) through G135 of the 165 d term. Additionally, for subsets of animals characterized at G90 and G135, immunohistochemical staining was performed, and 3D structure tensor analyses were used to identify the cellular processes that most closely parallel changes in water diffusion anisotropy with cerebral cortical maturation. Strong correlations were found between maturation of dendritic arbors on the cellular level and the loss of diffusion anisotropy with cortical development. In turn, diffusion anisotropy changes were strongly associated both regionally and temporally with cortical folding. Notably, the regional and temporal dependence of diffusion anisotropy and folding were distinct from the patterns observed for cerebral cortical surface area expansion. These findings strengthen the link proposed in previous studies between cellular-level changes in dendrite morphology and noninvasive diffusion MRI measurements of the developing cerebral cortex and support the possibility that, in gyroencephalic species, structural differentiation within the cortex is coupled to the formation of gyri and sulci.SIGNIFICANCE STATEMENTAbnormal brain morphology has been found in populations with neurodevelopmental disorders. However, the mechanisms linking cellular level and macroscopic maturation are poorly understood, even in normal brains. This study contributes new understanding to this subject using serialin uteroMRI measurements of rhesus macaque fetuses, from which macroscopic and cellular information can be derived. We found that morphological differentiation of dendrites was strongly associated both regionally and temporally with folding of the cerebral cortex. Interestingly, parallel associations were not observed with cortical surface area expansion. These findings support the possibility that perturbed morphological differentiation of cells within the cortex may underlie abnormal macroscopic characteristics of individuals affected by neurodevelopmental disorders.
Visual Stimulus Speed Does Not Influence the Rapid Emergence of Direction Selectivity in Ferret Visual Cortex
Authors: Ritter Neil J. , Anderson Nora M. , Van Hooser Stephen D. 
Published: January 2017

Sensory experience is necessary for the development of some receptive field properties of neurons in primary sensory cortical areas. However, it remains unclear whether the parameters of an individual animal's experience play an instructive role and influence the tuning parameters of cortical sensory neurons as selectivity emerges, or rather whether experience merely permits the completion of processes that are fully seeded at the onset of experience. Here we have examined whether the speed of visual stimuli that are presented to visually naive ferrets can influence the parameters of speed tuning and direction selectivity in cortical neurons. Visual experience is necessary for the development of direction selectivity in carnivores. If, during development, cortical neurons had the flexibility to choose from among different inputs with a range of spatial positions and temporal delays, then correlation-based plasticity mechanisms could instruct the precise spatiotemporal selectivity that underlies speed tuning and direction selectivity, and the parameters of an individual animal's experience would influence the tuning that emerges. Alternatively, the tuning parameters of these neurons may already be established at the onset of visual experience, and experience may merely permit the expression of this tuning. We found that providing different groups of animals with either slow (12.5 deg/s) or fast (50 deg/s) visual stimuli resulted in emergence of direction selectivity, but that speed tuning and direction selectivity were similar in the two groups. These results are more consistent with a permissive role for experience in the development of direction selectivity.SIGNIFICANCE STATEMENTThe proper development of brain circuits and neural response properties depends on both nature (factors independent of experience) and nurture (factors dependent on experience). In this study, we examined whether the quality of visual experience of an individual animal influences the development of basic sensory detectors in primary visual cortex. We found that, although visual experience is required for the development of direction selectivity, tuning for stimulus speed could not be altered by specific experience with slow or fast stimuli. These results suggest that the tuning parameters for direction selectivity are specified independently of an animal's sensory experience, and that a range of experiences can promote the proper mature expression of direction selectivity in primary visual cortex.
Adaptive resistance of melanoma cells to RAF inhibition via reversible induction of a slowly dividing de‐differentiated state
Authors: Fallahi‐Sichani Mohammad , Becker Verena , Izar Benjamin , Baker Gregory J , Lin Jia‐Ren , Boswell Sarah A , Shah Parin , Rotem Asaf , Garraway Levi A , Sorger Peter K 
Published: January 2017

AbstractTreatment of BRAF‐mutant melanomas with MAP kinase pathway inhibitors is paradigmatic of the promise of precision cancer therapy but also highlights problems with drug resistance that limit patient benefit. We use live‐cell imaging, single‐cell analysis, and molecular profiling to show that exposure of tumor cells to RAF/MEK inhibitors elicits a heterogeneous response in which some cells die, some arrest, and the remainder adapt to drug. Drug‐adapted cells up‐regulate markers of the neural crest (e.g., NGFR), a melanocyte precursor, and grow slowly. This phenotype is transiently stable, reverting to the drug‐naïve state within 9 days of drug withdrawal. Transcriptional profiling of cell lines and human tumors implicates a c‐Jun/ECM/FAK/Src cascade in de‐differentiation in about one‐third of cell lines studied; drug‐induced changes in c‐Jun and NGFR levels are also observed in xenograft and human tumors. Drugs targeting the c‐Jun/ECM/FAK/Src cascade as well as BET bromodomain inhibitors increase the maximum effect (Emax) of RAF/MEK kinase inhibitors by promoting cell killing. Thus, analysis of reversible drug resistance at a single‐cell level identifies signaling pathways and inhibitory drugs missed by assays that focus on cell populations.