bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lurbinectedin Inactivates the Ewing Sarcoma Oncoprotein EWS-FLI1 by Redistributing It within the Nucleus
Authors: Harlow Matt L. , Maloney Nichole , Roland Joseph , Guillen Navarro Maria Jose , Easton Matthew K. , Kitchen-Goosen Susan M. , Boguslawski Elissa A. , Madaj Zachary B. , Johnson Ben K. , Bowman Megan J. , D'Incalci Maurizio , Winn Mary E. , Turner Lisa , Hostetter Galen , Galmarini Carlos María , Aviles Pablo M. , Grohar Patrick J. 
Published: October 2016

Abstract
There is a great need to develop novel approaches to target oncogenic transcription factors with small molecules. Ewing sarcoma is emblematic of this need, as it depends on the continued activity of the EWS-FLI1 transcription factor to maintain the malignant phenotype. We have previously shown that the small molecule trabectedin interferes with EWS-FLI1. Here, we report important mechanistic advances and a second-generation inhibitor to provide insight into the therapeutic targeting of EWS-FLI1. We discovered that trabectedin functionally inactivated EWS-FLI1 by redistributing the protein within the nucleus to the nucleolus. This effect was rooted in the wild-type functions of the EWSR1, compromising the N-terminal half of the chimeric oncoprotein, which is known to be similarly redistributed within the nucleus in the presence of UV light damage. A second-generation trabectedin analogue lurbinectedin (PM01183) caused the same nuclear redistribution of EWS-FLI1, leading to a loss of activity at the promoter, mRNA, and protein levels of expression. Tumor xenograft studies confirmed this effect, and it was increased in combination with irinotecan, leading to tumor regression and replacement of Ewing sarcoma cells with benign fat cells. The net result of combined lurbinectedin and irinotecan treatment was a complete reversal of EWS-FLI1 activity and elimination of established tumors in 30% to 70% of mice after only 11 days of therapy. Our results illustrate the preclinical safety and efficacy of a disease-specific therapy targeting the central oncogenic driver in Ewing sarcoma. Cancer Res; 76(22); 6657–68. ©2016 AACR.
Genomic Approaches to Understanding Response and Resistance to Immunotherapy
Authors: Braun David A. , Burke Kelly P. , Van Allen Eliezer M. 
Published: October 2016

Abstract
Immunotherapy has led to a paradigm shift in the treatment of some malignancies, providing long-term, durable responses for patients with advanced cancers. However, such therapy has benefited only a subset of patients, with some patients failing to respond to treatment at all and others achieving a limited response followed by tumor progression. Understanding factors contributing to an effective response and further elucidating mechanisms of resistance will be crucial as these therapies are applied more broadly. Genomics-based approaches have significantly advanced the study of response and resistance to immunotherapy in general, and to immune checkpoint blockade more specifically. Here, we review how genomic and transcriptomic approaches have identified both somatic and germline positive correlates of response, including high mutational/neoantigen load and low intratumoral heterogeneity, among others. The genomic analysis of resistant tumors has additionally identified crucial factors involved in resistance to immune checkpoint blockade, including loss of PTEN and upregulation of other immune checkpoints. Overall, the continued use of genomic techniques at the point of care, combined with appropriate functional studies, would ideally lead to a better understanding of why certain patients respond to immune-based therapies, allowing clinicians to identify the subset of patients likely to benefit from such therapy, and potentially providing insight into how other therapies may be added in combination to increase the number of patients who may benefit from immunotherapy. Clin Cancer Res; 22(23); 5642–50. ©2016 AACR.
Immunotherapy in Endometrial Cancer: In the Nick of Time
Authors: Piulats Josep Maria , Matias-Guiu Xavier 
Published: October 2016

Abstract
Immunotherapy with checkpoint inhibitors is changing the face of oncology treatments for many tumors, and endometrial carcinoma may not be an exception. Several endometrial cancer groups from the molecular taxonomy are characterized by having an ultramutated/hypermutated genome, which could be the first Achilles' heel identified in this malignancy in decades. Clin Cancer Res; 22(23); 5623–5. ©2016 AACR.
See related article by Santin et al., p. 5682
IL2 Variant Circumvents ICOS+ Regulatory T-cell Expansion and Promotes NK Cell Activation
Authors: Sim Geok Choo , Liu Chengwen , Wang Ena , Liu Hui , Creasy Caitlin , Dai Zhimin , Overwijk Willem W. , Roszik Jason , Marincola Francesco , Hwu Patrick , Grimm Elizabeth , Radvanyi Laszlo 
Published: October 2016

AbstractClinical responses to high-dose IL2 therapy are limited due to selective expansion of CD4+CD25+Foxp3+ T-regulatory cells (Treg), especially ICOS+ Tregs, rather than natural killer (NK) cells and effector T cells. These ICOS+ Tregs are highly suppressive and constitutively express high levels of IL2Rα (CD25) and CD39. Here, we characterized the effect of a mutant form of IL2 (F42K), which preferentially binds to the lower affinity IL2Rβγ with reduced binding to CD25, on Tregs, effector NK cells, and T-cell subsets. Unlike wild-type (WT) IL2, F42K did not efficiently induce the expansion of highly suppressive ICOS+ Tregs in peripheral blood mononuclear cells (PBMC) from healthy controls and melanoma patients. Instead, it promoted the expansion of CD16+CD56+ NK cells and CD56hiCD16− NK cell subsets in both short- and long-term cultures, with enhanced Bcl-2 expression. Stimulation of PBMCs with F42K induced expression of more NK cell activation molecules, such as NKp30, NKp44, DNAM-1, NKG2D, 4-1BB/CD137, and Tim-3, than WT IL2. F42K induced greater upregulation of TRAIL, and NK-mediated cytolytic activity was increased against both autologous and HLA-mismatched melanoma cells compared with WT IL2. Gene expression analysis revealed distinct gene expression profiles stimulated by F42K, WT IL2, and IL15. F42K therapy in vivo also induced a dramatic reduction in the expansion of ICOS+ Tregs, promoted NK cell expansion, and inhibited melanoma tumor growth more efficiently than WT IL2 and more effectively than anti–CTLA-4. Our findings suggest that F42K could be a potential substitute for WT IL2 as a cytokine therapy for cancer. Cancer Immunol Res; 4(11); 983–94. ©2016 AACR.
The Influence of Synoptic Circulations and Local Processes on Temperature Anomalies at Three French Observatories
Authors: Dione Cheikh , Lohou Fabienne , Chiriaco Marjolaine , Lothon Marie , Bastin Sophie , Baray Jean-Luc , Yiou Pascal , Colomb Aurélie 
Published: October 2016

AbstractThe relative contribution of the synoptic-scale circulations to local and mesoscale processes was quantified in terms of the variability of midlatitude temperature anomalies from 2003 to 2013 using meteorological variables collected from three French observatories and reanalyses. Four weather regimes were defined from sea level pressure anomalies using National Centers for Environmental Prediction reanalyses with a K-means algorithm. No correlation was found between daily temperature anomalies and weather regimes, and the variability of temperature anomalies within each regime was large. It was therefore not possible to evaluate the effect of large scales on temperature anomalies by this method. An alternative approach was found with the use of the analogs method: the principle being that for each day of the considered time series, a set of days that had a similar large-scale 500-hPa geopotential height field within a fixed domain was considered. The observed temperature anomalies were then compared with those observed during the analog days: the closer the two types of series are to each other, the greater is the influence of the large scale. This method highlights a widely predominant influence of the large-scale atmospheric circulation on the temperature anomalies. It showed a potentially larger influence of the Mediterranean Sea and orographic flow on the two southern observatories. Low-level cloud radiative effects substantially modulated the variability of the daily temperature anomalies.
Randomized phase 2 trial of ixazomib and dexamethasone in relapsed multiple myeloma not refractory to bortezomib
Authors: Kumar Shaji K. , LaPlant Betsy R. , Reeder Craig B. , Roy Vivek , Halvorson Alese E. , Buadi Francis , Gertz Morie A. , Bergsagel P. Leif , Dispenzieri Angela , Thompson Melanie A. , Crawley Jamie , Kapoor Prashant , Mikhael Joseph , Stewart Keith , Hayman Suzanne R. , Hwa Yi L. , Gonsalves Wilson , Witzig Thomas E. , Ailawadhi Sikander , Dingli David , Go Ronald S. , Lin Yi , Rivera Candido E. , Rajkumar S. Vincent , Lacy Martha Q. 
Published: October 2016

Key Points
The combination of ixazomib and dexamethasone has clinical activity in patients with relapsed and or refractory multiple myeloma. Higher dose of ixazomib leads to improved response rates but with higher rates of treatment related adverse events.
Construing the ecological perspective of the Tai Dam as seen in ‘Sen Huen’ ritual manuscripts
Authors: Patpong Pattama 
Published: October 2016

AbstractThis paper is a part of the research project entitled “Transmission of ‘Sen Huen’ ritual as an intangible cultural heritage of Tai Dam ethnic group”. The Sen Huen ritual is a significant aspect of the Tai Dam’s ancestor worship. This ritual has to be conducted in a room set for ancestral spirits called "Image missing" and the ritual is required to be done every 2–3 years to avoid bad luck and receive good fortune and blessings, otherwise the descendants will suffer misfortunes such as illness, hardship and adversity. The theoretical framework applied to this study is Systemic Functional Linguistics, in particular the description of the system of transitivity, which is part of the ideational metafunction. The paper aims to investigate how the Tai Dam perception of local ecology is construed grammatically in the transitivity system. The system of transitivity is a resource for construing human experience of change or goings − on in the flow of events inside and around us. A quantum of change in the flow of events is construed as a configuration of a process involving one or more participants and attendant circumstances. The data were drawn from six Sen Huen ritual manuscripts which were collected from six Sen Huen ritual shamans residing in four provinces of Thailand: Phetchaburi, Ratchaburi, Nakhon Pathom, and Suphanburi provinces. The study reveals that there is a connection between the process and circumstance configurations expressing the Tai Dam ecological perspective. It illustrates a clear correlation between the semiotic model of time (month by month) and space (geographical space) that is construed by language and the material actions that are carried out by different participants (both human and non-human).
Prospective Longitudinal Analysis of 2-Hydroxyglutarate Magnetic Resonance Spectroscopy Identifies Broad Clinical Utility for the Management of Patients With IDH-Mutant Glioma
Authors: Choi Changho , Raisanen Jack M. , Ganji Sandeep K. , Zhang Song , McNeil Sarah S. , An Zhongxu , Madan Akshay , Hatanpaa Kimmo J. , Vemireddy Vamsidhara , Sheppard Christie A. , Oliver Dwight , Hulsey Keith M. , Tiwari Vivek , Mashimo Tomoyuki , Battiste James , Barnett Samuel , Madden Christopher J. , Patel Toral R. , Pan Edward , Malloy Craig R. , Mickey Bruce E. , Bachoo Robert M. , Maher Elizabeth A. 
Published: October 2016

Purpose Proton magnetic resonance spectroscopy (MRS) of the brain can detect 2-hydroxyglutarate (2HG), the oncometabolite produced in neoplasms harboring a mutation in the gene coding for isocitrate dehydrogenase ( IDH). We conducted a prospective longitudinal imaging study to determine whether quantitative assessment of 2HG by MRS could serve as a noninvasive clinical imaging biomarker for IDH-mutated gliomas. Patients and Methods 2HG MRS was performed in 136 patients using point-resolved spectroscopy at 3 T in parallel with standard clinical magnetic resonance imaging and assessment. Data were analyzed in patient cohorts representing the major phases of the glioma clinical course and were further subgrouped by histology and treatment type to evaluate 2HG. Histologic correlations were performed. Results Quantitative 2HG MRS was technically and biologically reproducible. 2HG concentration > 1 mM could be reliably detected with high confidence. During the period of indolent disease, 2HG concentration varied by less than ± 1 mM, and it increased sharply with tumor progression. 2HG concentration was positively correlated with tumor cellularity and significantly differed between high- and lower-grade gliomas. In response to cytotoxic therapy, 2HG concentration decreased rapidly in 1p/19q codeleted oligodendrogliomas and with a slower time course in astrocytomas and mixed gliomas. The magnitude and time course of the decrease in 2HG concentration and magnitude of the decrease in tumor volume did not differ between oligodendrogliomas treated with temozolomide or carmustine. Criteria for 2HG MRS were established to make a presumptive molecular diagnosis of an IDH mutation in gliomas technically unable to undergo a surgical procedure. Conclusion 2HG concentration as measured by MRS was reproducible and reliably reflected the disease state. These data provide a basis for incorporating 2HG MRS into clinical management of IDH-mutated gliomas.
Autonomous motivation, self-efficacy, and psychophysical wellbeing in a group of Polish breastfeeding mothers- preliminary communication
Authors: Kadzikowska-Wrzosek Romana 
Published: October 2016

Aim of the studyWomen’s decisions to quit breastfeeding are strongly influenced by feelings such as physical or psychological fatigue. The purpose of this study was to find out whether the autonomy of a breastfeeding mother’s motivation has an effect on her breastfeeding self-efficacy. Furthermore, the study examined the relationship between breastfeeding self-efficacy and such indicators of wellbeing as the frequency of experiencing positive and negative emotions, life satisfaction, and the occurrence of somatic symptoms.Subject or material and methodsThe sample consisted of 93 breastfeeding mothers ages 21 to 42. The survey was conducted online. The participants answered a questionnaire measuring their level of autonomous motivation to breastfeed, their breastfeeding self-efficacy, the level of experienced somatic stress,the frequency of experiencing positive and negative emotions and life satisfaction.ResultsThe results of the study confirmed that the more autonomous the mother’s motivation to breastfeed her baby, the higher her breastfeeding self-efficacy. Self-efficacy turned out to be a significant predictor of the frequency of experiencing positive emotions, negative emotions, and somatic stress symptoms. No relationship was found between the mothers’ self-efficacy and their reported life satisfaction.DiscussionAutonomous motivation in breastfeeding mothers has a positive effect on their breastfeeding self-efficacy. The higher level of breastfeeding self-efficacy, the more positive are breastfeeding mothers’ subjective experiences.ConclusionsShaping autonomous motivation in breastfeeding women has a positive effect on their breastfeeding self-efficacy High breastfeeding self-efficacy, which has a positive effect on the mother’s wellbeing, may also contribute to longer duration of breastfeeding.
Boundary conditions for semi-Lagrangian methods for the BGK model
Authors: Groppi Maria , Russo Giovanni , Stracquadanio Giuseppe 
Published: October 2016

Abstract
A new class of high-order accuracy numerical methods based on a semi-Lagrangian formulation for the BGK model of the Boltzmann equation has been recently proposed in [1]. In this paper semi-Lagrangian schemes for the BGK equation have been extended to treat boundary conditions, in particular the diffusive ones. Two different techniques are proposed, using or avoiding iterative procedures. Numerical simulations illustrate the accuracy properties of these approaches and the agreement with the results available in literature.
A mass conservative TR-BDF2 semi-implicit semi-Lagrangian DG discretization of the shallow water equations on general structured meshes of quadrilaterals
Authors: Tumolo Giovanni 
Published: October 2016

Abstract
As an extension of a previous work considering a fully advective formulation on Cartesian meshes, a mass conservative discretization approach is presented here for the shallow water equations, based on discontinuous finite elements on general structured meshes of quadrilaterals. A semi-implicit time integration is performed by employing the TR-BDF2 scheme and is combined with the semi-Lagrangian technique for the momentum equation only. Indeed, in order to simplify the derivation of the discrete linear Helmoltz equation to be solved at each time-step, a non-conservative formulation of the momentum equation is employed. The Eulerian flux form is considered instead for the continuity equation in order to ensure mass conservation. Numerical results show that on distorted meshes and for relatively high polynomial degrees, the proposed numerical method fully conserves mass and presents a higher level of accuracy than a standard off-centered Crank Nicolson approach. This is achieved without any significant imprinting of the mesh distortion on the solution.
Cost evaluation of clinical laboratory in Taiwan’s National Health System by using activity-based costing
Authors: Su Bin-Guang , Chen Shao-Fen , Yeh Shu-Hsing , Shih Po-Wen , Lin Ching-Chiang 
Published: October 2016

AbstractBackground:To cope with the government’s policies to reduce medical costs, Taiwan’s healthcare service providers are striving to survive by pursuing profit maximization through cost control. This article aimed to present the results of cost evaluation using activity-based costing performed in the laboratory in order to throw light on the differences between costs and the payment system of National Health Insurance (NHI).Methods:This study analyzed the data of costs and income of the clinical laboratory. Direct costs belong to their respective sections of the department. The department’s shared costs, including public expenses and administrative assigned costs, were allocated to the department’s respective sections. A simple regression equation was created to predict profit and loss, and evaluate the department’s break-even point, fixed cost, and contribution margin ratio.Results:In clinical chemistry and seroimmunology sections, the cost per test was lower than the NHI payment and their major laboratory tests had revenues with the profitability ratio of 8.7%, while the other sections had a higher cost per test than the NHI payment and their major tests were in deficit. The study found a simple linear regression model as follows: “Balance=–84,995+0.543×income (R2=0.544)”.Conclusions:In order to avoid deficit, laboratories are suggested to increase test volumes, enhance laboratory test specialization, and become marginal scale. A hospital could integrate with regional medical institutions through alliances or OEM methods to increase volumes to reach marginal scale and reduce laboratory costs, enhancing the level and quality of laboratory medicine.
Two cases of massive subchorionic thrombosis
Authors: Kaneko Megumi , Ebina Yasuhiko , Shinozaki Nanae , Yamasaki Yui , Deguchi Masashi , Yamada Hideto 
Published: October 2016

Abstract
Massive subchorionic thrombosis (MST) is defined as a massive thrombosis under the chorionic plate, and is responsible for obstetric complications. We encountered two cases of MST. Placental abruption was misdiagnosed by ultrasound examination in Case 1, and a cesarean section was performed at 33 weeks of gestation. Magnetic resonance imaging (MRI) at 21 weeks of gestation suggested MST in Case 2. A cesarean section was performed at 26 weeks’ gestation because of pregnancy-induced hypertension, fetal growth restriction and non-reassuring fetal status.
Development of forest cover mask to monitor the health condition of forests in Poland using long-term satellite observations
Authors: Bartold Maciej 
Published: October 2016

Abstract
The work presented here aims at developing cover mask for monitoring forest health in Poland using remote sensing data. The main objective was to assess the impact of using the mask on forest condition monitoring combined with vegetation indices obtained from long-term satellite data. In this study, a new mask developed from the CORINE Land Cover 2012 (CLC2012) database is presented and its one-kilometer pixel size matched to low-resolution data derived from SPOT VEGETATION satellite registrations. For vegetation mapping, only pixels with a cover ≥ 50% of broad-leaved and mixed forests defined by CLC2012 were taken into account. The masked pixels were used to evaluate spatial variability in eight Natural-Forest Regions (NFRs). The largest coverages by masked forests were obtained in Sudetian (65.7%), Carpathian (65.9%) and Baltic (51.3%) regions. For other forest regions the coverage was observed to be around 30-50%.
Time-series of the Normalized Difference Vegetation Index (NDVI) comprising SPOT VEGETATION images from 1998 until 2014 were computed and cross-comparison analyses on ≥ 50% and < 50% forest cover masks brought up frequent differences at a level higher than 0.05 NDVI in seven out of eight NFRs. An exception is the Sudetian region, where the data was highly consistent. Furthermore, the Mann-Whitney U non-parametric test revealed statistically significant differences in two regions: Baltic and Masurian-Podlasie NFR. The comparative analysis of NDVI confirmed that there is a need for additional investigation of the quality of newly developed forest mask combined with vegetation and meteorological data.
Psyhical effort, energy expediture, and motivation in structured and unstructured active video games: a randomized controlled trial
Authors: De Brito-Gomes Jorge Luiz , Perrier-Melo Raphael José , Melo de Oliveira Saulo Fernandes , De Sá Pereira Guimarães Fernando José , Costa Manoel da Cunha 
Published: October 2016

PurposeThe goals of the study were: a) to compare the way that two types of active video games (AVG) influenced physical
effort and motivation in young adults; b) to compare direct and indirect instruments and use an indirect instrument (heart
rate analysis) as a practical tool to verify physical effort in AVGsMethodsMethods. Initially, 16 healthy but physically inactive young
adult males with no AVGs experience took part in the randomized control trial. After the baseline assessments of blood pressure
(BP), heart rate (HR), and aerobic capacity (AE), the participants were randomized into two groups: structured AVG (<i>n</i> = 6) and
unstructured AVG (<i>n</i> = 7) (3 dropouts). They played 3 sessions a week, during 6 weeks. Direct and indirect metabolic measurements
were made. To compare direct and indirect AE, Student t-test was used for related samples. Changes (group × time) in HR,
perceived exertion (PE), calculated energy expenditure (EE), calculated metabolic equivalent (MET), and motivation (points)
were assessed with the two-way analysis of varianceResultsThere were no differences between direct and indirect AE (36.0
± 5.2 vs 33.9 ± 6.0 ml/kg/min: unstructured; 39.0 ± 5.9 vs 37.7 ± 5.9 ml/kg/min; <i>p</i> > 0.05). No differences were observed in
maximal HR, PE, or motivation (<i>p</i> > 0.05). Statistically significant differences referred to average HR, MET, and EE over the
sessions (<i>p</i> < 0.05). HR and EE values were higher in structured than in unstructured AVGsConclusionsHR and EE responses
of structured AVGs turned out higher than those of unstructured AVGs, and the measurements proved efficient to analyse
physical effort in AVGs in a long-term perspective