bluuebunny/crossref_metadata_2025_split huggingface dataset:
Class 1, 2, and 3BRAF-Mutated Metastatic Colorectal Cancer: A Detailed Clinical, Pathologic, and Molecular Characterization
Authors: Schirripa Marta , Biason Paola , Lonardi Sara , Pella Nicoletta , Pino Maria Simona , Urbano Federica , Antoniotti Carlotta , Cremolini Chiara , Corallo Salvatore , Pietrantonio Filippo , Gelsomino Fabio , Cascinu Stefano , Orlandi Armando , Munari Giada , Malapelle Umberto , Saggio Serena , Fontanini Gabriella , Rugge Massimo , Mescoli Claudia , Lazzi Stefano , Reggiani Bonetti Luca , Lanza Giovanni , Dei Tos Angelo Paolo , De Maglio Giovanna , Martini Maurizio , Bergamo Francesca , Zagonel Vittorina , Loupakis Fotios , Fassan Matteo 
Published: April 2019

AbstractPurpose:BRAF mutations are grouped in activating RAS-independent signaling as monomers (class 1–V600E) or as dimers (class 2–codons 597/601), and RAS-dependent with impaired kinase activity (class 3–codons 594/596). Although clinical, pathologic, and molecular features of V600EBRAF-mutated metastatic colorectal cancer (mCRC) are well known, limited data are available from the two other classes.Experimental Design:Data from 117 patients with BRAF (92 class 1, 12 class 2, and 13 class 3)-mutated mCRC were collected. A total of 540 BRAF wt mCRCs were included as control. IHC profiling was performed to determine the consensus molecular subtypes (CMS), cytokeratin 7/20 profiles, tumor-infiltrating lymphocyte infiltration, and BM1/BM2 categorization. Overall survival (OS) and progression-free survival were evaluated by Kaplan–Meier and log-rank test.Results:Class 3 BRAF-mutated mCRC was more frequently left sided (P = 0.0028), pN0 (P = 0.0159), and without peritoneal metastases (P = 0.0176) compared with class 1, whereas class 2 cases were similar to class 1. Hazard ratio for OS, as compared with BRAF wt, was 2.38 [95% confidence interval (CI), 1.61–3.54] for class 1, 1.90 (95% CI, 0.85–4.26) for class 2, and 0.93 (95% CI, 0.51–1.69) for class 3 (P &lt; 0.0001). Class 2 and 3 tumors were all assigned to CMS2-3. A higher median CD3/CD8-positive lymphocyte infiltration was observed in BRAF-mutated class 2 (P = 0.033) compared with class 3 cases.Conclusions:For the first time, different clinical and pathologic features and outcome data were reported according to the three BRAF mutation classes in mCRC. Specific targeted treatment strategies should be identified in the near future for such patients.
p21CIP1 Promotes Mammary Cancer–Initiating Cells via Activation of Wnt/TCF1/CyclinD1 Signaling
Authors: Benard Outhiriaradjou , Qian Xia , Liang Huizhi , Ren Zuen , Suyama Kimita , Norton Larry , Hazan Rachel B. 
Published: April 2019

Abstract

Cancer stem cells (CSC) generate and sustain tumors due to tumor-initiating potential, resulting in recurrence or metastasis. We showed that knockout of the cell-cycle inhibitor, p21CIP1, in the PyMT mammary tumor model inhibits metastasis; however the mechanism remained unknown. Here, we show a pivotal role for p21 in potentiating a cancer stem–like phenotype. p21 knockout in PyMT mammary tumor cells caused dramatic suppression of CSC properties involving tumorsphere formation, ALDH1 activity, and tumor-initiating potential, which were in turn rescued by p21 overexpression into PyMT/p21 knockout cells. Interestingly, p21 knockout dramatically suppresses Wnt/β-catenin signaling activity, leading to striking inhibition of LEF1 and TCF1 expression. TCF1 knockdown in PyMT cells suppressed tumorsphere formation due to Cyclin D1 attenuation. These data demonstrate that p21 promotes a CSC-like phenotype via activation of Wnt/TCF1/Cyclin D1 signaling.

Implications:
p21 is a strong promoter of mammary CSCs.
Derecho Evolving from a Mesocyclone—A Study of 11 August 2017 Severe Weather Outbreak in Poland: Event Analysis and High-Resolution Simulation
Authors: Taszarek Mateusz , Pilguj Natalia , Orlikowski Juliusz , Surowiecki Artur , Walczakiewicz Szymon , Pilorz Wojciech , Piasecki Krzysztof , Pajurek Łukasz , Półrolniczak Marek 
Published: April 2019

AbstractThis study documents atmospheric conditions, development, and evolution of a severe weather outbreak that occurred on 11 August 2017 in Poland. The emphasis is on analyzing system morphology and highlighting the importance of a mesovortex in producing the most significant wind damages. A derecho-producing mesoscale convective system (MCS) had a remarkable intensity and was one of the most impactful convective storms in the history of Poland. It destroyed and partially damaged 79 700 ha of forest (9.8 million m3 of wood), 6 people lost their lives, and 58 were injured. The MCS developed in an environment of high 0–3-km wind shear (20–25 m s−1), strong 0–3-km storm relative helicity (200–600 m2 s−2), moderate most-unstable convective available potential energy (1000–2500 J kg−1), and high precipitable water (40–46 mm). Within the support of a midtropospheric jet, the MCS moved northeast with a simultaneous northeastward inflow of warm and very moist air, which contributed to strong downdrafts. A mesocyclone embedded in the convective line induced the rear inflow jet (RIJ) to descend and develop a bow echo. In the mature stage, a supercell evolved into a bookend vortex and later into a mesoscale convective vortex. Swaths of the most significant wind damage followed the aforementioned vortex features. A high-resolution simulation performed with initial conditions derived from GFS and ECMWF global models predicted the possibility of a linear MCS with widespread damaging wind gusts and embedded supercells. Simulations highlighted the importance of cloud cover in the preconvective environment, which influenced the placement and propagation of the resulting MCS.
RNA-binding proteins in hematopoiesis and hematological malignancy
Authors: Hodson Daniel J. , Screen Michael , Turner Martin 
Published: April 2019

Abstract
RNA-binding proteins (RBPs) regulate fundamental processes, such as differentiation and self-renewal, by enabling the dynamic control of protein abundance or isoforms or through the regulation of noncoding RNA. RBPs are increasingly appreciated as being essential for normal hematopoiesis, and they are understood to play fundamental roles in hematological malignancies by acting as oncogenes or tumor suppressors. Alternative splicing has been shown to play roles in the development of specific hematopoietic lineages, and sequence-specific mutations in RBPs lead to dysregulated splicing in myeloid and lymphoid leukemias. RBPs that regulate translation contribute to the development and function of hematological lineages, act as nodes for the action of multiple signaling pathways, and contribute to hematological malignancies. These insights broaden our mechanistic understanding of the molecular regulation of hematopoiesis and offer opportunities to develop disease biomarkers and new therapeutic modalities.
Clonotypic heterogeneity in cutaneous T-cell lymphoma (mycosis fungoides) revealed by comprehensive whole-exome sequencing
Authors: Iyer Aishwarya , Hennessey Dylan , O’Keefe Sandra , Patterson Jordan , Wang Weiwei , Salopek Thomas , Wong Gane Ka-Shu , Gniadecki Robert 
Published: April 2019

Abstract
Mycosis fungoides (MF), the most common type of cutaneous T-cell lymphoma, is believed to represent a clonal expansion of a transformed skin-resident memory T cell. T-cell receptor (TCR) clonality (ie, identical sequences of rearranged TCRα, TCRβ, and TCRγ), the key premise of this hypothesis, has been difficult to document conclusively because malignant cells are not readily distinguishable from the tumor-infiltrating reactive lymphocytes that contribute to the TCR clonotypic repertoire of MF. Here, we have successfully adopted targeted whole-exome sequencing (WES) to identify the repertoire of rearranged TCR genes in tumor-enriched samples from patients with MF. Although some of the investigated MF biopsies had the expected frequency of monoclonal rearrangements of TCRγ corresponding to that of tumor cells, the majority of the samples presented multiple TCRγ, TCRα, and TCRβ clonotypes by WES. Our findings are compatible with the model in which the initial malignant transformation in MF does not occur in mature memory T cells but rather at the level of T-lymphocyte progenitors before TCRβ or TCRα rearrangements. We have also shown that WES can be combined with whole-transcriptome sequencing in the same sample, which enables comprehensive characterization of the TCR repertoire in relation to tumor content. WES/whole-transcriptome sequencing might be applicable to other types of T-cell lymphomas to determine clonal dominance and clonotypic heterogeneity in these malignancies.
Critical Analysis of Hematology and Oncology Fellowship Web Sites in the United States
Authors: Ruddell Jack H. , Ahmed Shaan A. , Tang Oliver Y. , Schiffman Fred J. , Quesenberry Matthew I. , Eltorai Adam E.M. 
Published: April 2019

PURPOSE: Prospective hematology-oncology fellowship applicants use program Web sites as a critical source of information. The purpose of this study was to evaluate the current content and comprehensiveness of hematology-oncology fellowship Web sites and to identify specific areas for improvement. METHODS: This study assessed the presence of 27 commonly evaluated program and application and curriculum and training informational items for Web sites of all accredited hematology-oncology fellowship programs in 2018. The comprehensiveness score was calculated as the number of items present on a fellowship Web site out of 27 and was compared by program region and size using analysis of variance and two-tailed t tests. RESULTS: Of the 143 fellowship Web sites evaluated, the mean comprehensiveness score was 39.3% (10.6 ± 3.8 out of 27). Programs contained a mean of 42.1% (5.9 ± 2.3 out of 14) of program and application and 36.2% (4.7 ± 2.1 out of 13) of curriculum and training items. The program and application items most common among Web sites were program coordinator contact and faculty listing (83.2% and 74.1% of Web sites, respectively), whereas social events and salary and benefits were less common (31.5% and 20.3% of Web sites, respectively). Prevalent curriculum and training items were research publications and activity and rotation scheduling (86.0% and 81.1% of Web sites, respectively), whereas board examination pass rates and fellow call duties were uncommon (4.2% and 15.4% of Web sites, respectively). Large programs were associated with greater overall Web site items compared with small programs (43.0% [11.6 ± 4.1 out of 27] v 35.9% [9.7 ± 3.3 out of 27]; P = .003). CONCLUSION: Hematology-oncology fellowship Web sites vary considerably in the level and nature of content they contain. Because applicants rely on online information for decision making, more comprehensive online content may promote a better fit between program and applicant. There is room for improvement in hematology-oncology fellowship Web sites, and programs may consider directing resources toward enhancing these Web sites.
Elevated Lipoprotein(a) Levels Lower ABCA1 Cholesterol Efflux Capacity
Authors: Tavori Hagai , Fenton Alexandra M , Plubell Deanna L , Rosario Sara , Yerkes Elisabeth , Gasik Rayna , Miles Joshua , Bergstrom Paige , Minnier Jessica , Fazio Sergio , Pamir Nathalie 
Published: April 2019

AbstractContextElevated serum lipoprotein(a) [Lp(a)] levels are associated with increased cardiovascular disease risk. ABCA1-mediated cholesterol efflux from macrophages may be an antiatherogenic process. Plasminogen (PLG) is a driver of ABCA1-mediated cholesterol efflux, and its action is inhibited by purified human Lp(a).ObjectiveTo determine the effects of Lp(a) in human serum on ABCA1 cholesterol efflux.MethodsCholesterol efflux capacity (CEC) was measured with two different cell-culture models using serum from 76 patients with either low (<50 mg/dL) or high (>50 mg/dL) Lp(a) levels.ResultsUsing cAMP-stimulated J774 macrophages or baby hamster kidney fibroblasts overexpressing human ABCA1, we show that CEC was lower in patients with high Lp(a) levels compared with patients with low levels (−30.6%, P = 0.002 vs −24.1%, P < 0.001, respectively). Total-serum CEC negatively correlated with Lp(a) levels (r = −0.433, P = 0.0007 vs r = −0.505, P = 0.0011, respectively). These negative associations persisted after adjusting for serum cholesterol, age, sex, and statin use in a multiple linear regression model (adjusted R2 = 0.413 or 0.405, respectively) and were strengthened when further adjusting for the interaction between Lp(a) and PLG levels (adjusted R2 = 0.465 and 0.409, respectively). Total-serum and isolated Lp(a) from patients with high Lp(a) inhibited PLG-mediated ABCA1 cholesterol efflux.ConclusionTotal-serum CEC is reduced in patients with high Lp(a) levels. This is in part due to the inhibition of PLG-mediated ABCA1 cholesterol efflux by Lp(a). Our findings suggest an atherogenic role for Lp(a) through its ability to inhibit CEC.
The impact of using primaquine without prior G6PD testing: a case series describing the obstacles to the medical management of haemolysis
Authors: Chu Cindy S. , Bancone Germana , Soe Nay Lin , Carrara Verena I. , Gornsawun Gornpan , Nosten François 
Published: April 2019

Radical cure of Plasmodium vivax malaria in glucose-6-phosphate dehydrogenase (G6PD) deficient individuals employs weekly primaquine dosing. This is the only recommended regimen for this patient sub-group. If national malaria programs mandate daily primaquine dosing (the recommended regimen for G6PD normal individuals), then G6PD testing before prescription is necessary to avoid iatrogenic haemolysis in G6PD deficient individuals. In this case series, two P. vivax infected patients with unknown G6PD status from two different countries were prescribed primaquine as per national malaria program guidelines. During treatment both patients presented to the clinic with symptoms of anaemia after taking primaquine incorrectly. The clinical management of the iatrogenic severe haemolysis that occurred in these patients demonstrates the various adverse effects primaquine can cause, that other common medical treatments also have haemolytic potential, and how the diagnosis of G6PD deficiency can be elusive during acute haemolysis. Health care providers should provide careful instructions about primaquine dosing, be watchful for haemolysis, and have a high index of suspicion for G6PD deficiency in the presence of haemolysis if the G6PD status is previously unknown.
Dětská pojetí vybraných environmentálních fenoménů u žáků 1. a 2. stupně základní školy
Authors: Pavlátová Věra 
Published: April 2019

Představa učitele, které pojmy (= fenomény) znamenají pro žáky problém, je nezbytným předpokladem úspěšné realizace výuky. Je ale možné, že žáci vidí obtížnost fenoménů jinak než učitel. V našem výzkumu porovnáme názor na vnímání obtížnosti 20 vybraných environmentálních fenoménů u učitelů 10 základních škol (N=60; výzkumným nástrojem byl dotazník) a u jejich žáků (N=1341; výzkumným nástrojem byl kognitivní test). Kromě vnímání obtížnosti nás také zajímalo porozumění významu a pojetí tohoto porozumění.
Za využití metodologické triangulace jsme dále pracovali z 8 fenomény, které se ukázaly dle výsledků kognitivního testu pro žáky nejvíce obtížnými, a to následným, kvalitativním výzkumem, kde byla výzkumným nástrojem pojmová mapa (N=79) doplněná u některých respondentů (= R) následným rozhovorem (N=4).
Byl prokázán statisticky významný rozdíl v porozumění významu fenoménů v závislosti na použitém výzkumném nástroji (Z=6,8, p <0,001). Jsou zde diskutovány možné důvody pro dětská pojetí a miskoncepce, které dle výsledku výzkumu, přetrvávají s věkem žáků.
Multiple Closed Geodesics on Positively Curved Finsler Manifolds
Authors: Wang Wei 
Published: April 2019

Abstract
In this paper, we prove that on every Finsler manifold

(
M
,
F
)

{(M,F)}

with reversibility λ and flag curvature K satisfying

(

λ

λ
+
1

)

2

<
K
≤
1

{(\frac{\lambda}{\lambda+1})^{2}<K\leq 1}

, there exist

[

dim
⁡
M

+
1

2

]

{[\frac{\dim M+1}{2}]}

closed geodesics. If the number of closed geodesics is finite, then there exist

[

dim
⁡
M

2

]

{[\frac{\dim M}{2}]}

non-hyperbolic closed geodesics. Moreover, there are three closed geodesics on

(
M
,
F
)

{(M,F)}

satisfying the above pinching condition when

dim
⁡
M

=
3

{\dim M=3}

.
Envelope wages, hidden production and labor productivity
Authors: Di Nola Alessandro , Kocharkov Georgi , Vasilev Aleksandar 
Published: April 2019

Abstract
We evaluate the relative importance of aggregate labor productivity versus income taxes and social contributions for tax compliance in an economy with a large degree of informality. Empirical evidence points out that tax evasion in Europe happens through partially concealing wages and profits in formally registered enterprises. To this end, we build a model in which employer-employee pairs of heterogeneous productive capacities make joint decisions on the degree of tax evasion. The quantitative model is used to analyze the case of Bulgaria which has the largest informal economy in Europe and underwent a number of important tax reforms over the period 2000–2014, including the introduction of a flat income tax in 2008. The estimation strategy relies on matching the empirical series for the size of the informal economy and other aggregate outcomes for 2000–2014. Our counterfactual experiments show that the most important factor for the changing size of the informal economy is labor productivity, which accounts for more than 75% of the change. The variation in corporate income tax accounts for the rest. We find that the 2008 flat tax reform did not play any visible role in coping with informality.
Wege zur Optimierung des Forschungsdatenmanagements – Die Forschungsperspektive des PODMAN-Projekts
Authors: Förster André , Blask Katarina , Lemaire Marina 
Published: April 2019

ZusammenfassungAusgehend von der Notwendigkeit, die Integration von Forschungsdatenmanagement in bestehende Forschungsprozesse zu optimieren, stellt dieser Beitrag das BMBF-Projekt PODMAN vor. Es kombiniert Konzepte des Prozessmanagements und der Psychologie zu einem prototypischen Forschungsdatenmanagement-Modell. Hierbei bezieht es Forscher aus den Geisteswissenschaften und der Psychologie sowie die Infrastruktureinrichtungen an der Universität Trier und dem Zentrum für Psychologische Information und Dokumentation (ZPID) mit ein.
Open Access aus der Sicht von Verlagen
Authors: Kaier Christian , Lackner Karin 
Published: April 2019

ZusammenfassungFördergeber, Universitäten und Bibliotheken drängen seit Jahren auf einen freien Zugang zu wissenschaftlichen Publikationen. Während mit immer mehr großen Verlagen Open-Access-Abkommen ausverhandelt werden, waren kleinere Verlage bislang in den Debatten zur Open-Access-Transformation kaum vertreten. Wir befragten daher Vertreter von 82 kleinen und mittelständischen Wissenschaftsverlagen zu ihren Erfahrungen, Einstellungen und Angeboten zu Open Access. Es zeigte sich, dass Open Access für diese Verlage und ihre Autoren wichtiger wird, allerdings bestehen abhängig von Verlagsgröße, Fachbereichen und Literaturtypen deutliche Unterschiede bei Einstellungen und Kenntnissen bezüglich Open Access. Zentrale Anforderungen für eine Umstellung ihrer Publikationstätigkeit auf Open Access sind für Verlage ausreichende Finanzierung, mehr Standardisierung sowie eine bessere Zusammenarbeit und Kommunikation mit anderen Stakeholdern.
Archivierungsstrategien anpassen – Herausforderungen und Lösungen für die Archivierung und Sekundärnutzung von ethnologischen Forschungsdaten
Authors: Sterzer Wjatscheslaw , Kretzer Susanne 
Published: April 2019

ZusammenfassungEthnologische Forschungsdaten enthalten in der Regel sensible und schutzwürdige, häufig personenbezogene Daten, die hohe Anforderungen an die Archivierung und Aufbereitung für die Sekundärnutzung stellen. Angemessene und flexible Workflows erlauben eine adäquate Darstellung der Studien in einer sicheren technischen Umgebung und berücksichtigen forschungspraktische, ethische und rechtliche Aspekte. Für den deutschen Raum hat sich das Datenservicezentrum Qualiservice als einzige Möglichkeit erwiesen, um eine adäquate Archivierung für solche Daten zu ermöglichen. Der Beitrag beschreibt die Anforderungen für die Archivierung von ethnologischen Forschungsdaten und die Workflows, die von Qualiservice für den ethnologischen Bereich adaptiert werden können.
MyCoRe macht Forschungsdaten FAIR
Authors: Oeltjen Wiebke , Neumann Kathleen , Stahl Ulrike , Stephan Robert 
Published: April 2019

ZusammenfassungForschungsdaten werden in Repositorien gespeichert und zur Nachnutzung erhalten. Dies setzt voraus, dass die Repositorien bestimmte Prinzipien einhalten. Die FAIR-Leitprinzipien besagen, dass wissenschaftliche Daten auffindbar, zugänglich, interoperabel und wiederverwendbar sein sollen. In diesem Artikel wird gezeigt, dass die Open-Source-Software MyCoRe geeignet ist, Repositorien bereitzustellen, die die FAIR-Prinzipien erfüllen. Dazu werden drei MyCoRe-Anwendungen, die Forschungsdaten verwalten und bereitstellen, untersucht und bewertet.
Methods to Evaluate Lifecycle Models for Research Data Management
Authors: Weber Tobias , Kranzlmüller Dieter 
Published: April 2019

AbstractLifecycle models for research data are often abstract and simple. This comes at the danger of oversimplifying the complex concepts of research data management. The analyses of 90 different lifecycle models lead to two approaches to assess the quality of these models. While terminological issues make direct comparisons of models hard, an empirical evaluation seems possible.
Die Bibliographische Datenbank zur Geschichtsschreibung im Osmanischen Europa (15. bis 18. Jh.)
Authors: Strotmann Vivian 
Published: April 2019

ZusammenfassungDas DFG-Projekt „Bibliographische Datenbank zur Geschichtsschreibung im Osmanischen Europa (15. bis 18. Jh.)“ (HOE) wurde zwischen 2015 und 2018 kooperativ vom Lehrstuhl für die Geschichte des Osmanischen Reiches und der Türkei (ORT) und der Universitätsbibliothek (UB) der Ruhr-Universität Bochum durchgeführt. Der vorliegende Artikel gibt einen Überblick über die dem Systemdesign zugrundeliegenden konzeptionellen und technischen Überlegungen und beschreibt die Rolle der Universitätsbibliothek in einer Kooperation mit mehreren wissenschaftlichen Partnern.Teil 1.1 des Textes und die korrespondierenden Internetseiteninhalte beruhen auf Ausführungen von Ovidiu-Victor Olar, Mitglied des wissenschaftlichen Projektteilteams.
Framework Information Literacy – Aspekte aus Theorie, Forschung und Praxis
Authors: Sauerwein Tessa 
Published: April 2019

ZusammenfassungDas Framework for Information Literacy for Higher Education bietet neue, ganzheitliche Möglichkeiten für die Konzeption, Gestaltung und Förderung von Informationskompetenz. Dieser Beitrag zeigt, wie das Rahmenmodell der amerikanischen Association of College & Research Libraries (ACRL) für Schulungsangebote in Deutschland genutzt werden kann. Vorgestellt werden Aspekte aus Theorie und Forschung sowie ein adaptives Best-Practice-Beispiel der Universitätsbibliothek Bamberg. Die prämierten Framework Information Literacy Lessons (FILL) liefern nachhaltige Erkenntnisse zum wissenschaftlichen Arbeiten. Das fördert Kollaboration, Kommunikation sowie forschendes Lernen und gestaltet Zukunft. Teaching Libraries können so für die digitale Informationswelt kritisch sensibilisieren.