bluuebunny/crossref_metadata_2025_split huggingface dataset:
RELAP5-3D Three-Dimensional Analysis Based on PHÉNIX Dissymmetric Transient Test
Authors: Narcisi Vincenzo , Giannetti Fabio , Subioli Andrea , Del Nevo Alessandro , Caruso Gianfranco 
Published: September 2019

Abstract
Before the final shutdown of the PHÉNIX fast reactor, the CEA carried out a final set of experimental tests to gather data and additional knowledge on relevant sodium fast reactors (SFR) operation and safety aspects. One of these experiments conducted was the dissymmetrical configuration test, which was selected as benchmark transient within the H2020 SESAME project. ENEA and Sapienza University of Rome are participating in the benchmark using the RELAP5-3D© code. The thermal hydraulic analysis focuses on adequate core cooling prediction in accidental scenario. With the goal of investigating asymmetric thermal hydraulic behavior inside of the reactor pool, two different nodalization approaches have been applied for the RELAP5-3D model, which adopt the same geometrical scheme for the primary flow path, with the exception of the hot and cold pools and the core bypass. The first scheme has been developed using vertical parallel pipes with cross junctions for the hot and cold pools and an equivalent pipe to reproduce the core bypass. The second model includes a multidimensional (MULTID) component, which simulates the pools and provides a detailed nodalization of the core bypass. This study aims at assessing whether the two modeling approaches are equally capable to predict the asymmetrical temperature evolution over the test, caused by the azimuthal asymmetry of the boundary conditions. Blind calculation results are presented and discussed. The paper will be a first step toward the RELAP5-3D code assessment against the experimental results collected as part of the PHÉNIX dissymmetric test.
Time-Domain Bloch Boundary Conditions for Efficient Simulation of Thermoacoustic Limit Cycles in (Can-)Annular Combustors
Authors: Haeringer Matthias , Polifke Wolfgang 
Published: September 2019

Abstract
Thermo-acoustic eigenmodes of annular or can-annular combustion chambers, which typically feature a discrete rotational symmetry, may be computed in an efficient manner by utilizing the Bloch-wave theory. Unfortunately, the application of the Bloch-wave theory to combustion dynamics has hitherto been limited to the frequency domain. In this study, we present a time-domain formulation of Bloch boundary conditions (BBC), which allows to employ them in time domain simulations, e.g., computational fluid dynamics (CFD) simulations. The BBCs are expressed as acoustic scattering matrices and translated to complex-valued state-space systems. In a hybrid approach an unsteady, compressible CFD simulation of the burner-flame zone is coupled via characteristic-based state-space boundary conditions to a reduced order model of the combustor acoustics that includes BBCs. The acoustic model with BBC accounts for cross-can acoustic coupling and the discrete rotational symmetry of the configuration, while the CFD simulation accounts for the nonlinear flow–flame acoustic interactions. This approach makes it possible to model limit cycle oscillations of (can-)annular combustors at drastically reduced computational cost compared to CFD simulations of the full configuration and without the limitations of weakly nonlinear approaches that utilize a flame describing function. In this study, the suggested approach is applied to a generic multican combustor. Results agree well with a fully compressible CFD simulation of the complete configuration.
Non-Axisymmetric Flows and Rotordynamic Forces in an Eccentric Shrouded Centrifugal Compressor—Part 1: Measurement
Authors: Song Jieun , Kim Suyong , Park Tae Choon , Cha Bong-Jun , Lim Dong Hun , Hong Joo Sung , Lee Tae Wook , Song Seung Jin 
Published: September 2019

Abstract
Centrifugal compressors can suffer from rotordynamic instability. While individual components (e.g., seals, shrouds) have been previously investigated, an integrated experimental or analytical study at the compressor system level is scarce. For the first time, non-axisymmetric pressure distributions in a statically eccentric shrouded centrifugal compressor with eye-labyrinth seals have been measured for various eccentricities. From the pressure measurements, direct and cross-coupled stiffness coefficients have been determined. Thus, the contributions of the pressure perturbations in the shroud cavity and labyrinth seals have been simultaneously investigated. The cross-coupled stiffness coefficients in the shroud and labyrinth seals are both positive and one order of magnitude larger than the direct stiffness coefficients. Furthermore, in the tested compressor, contrary to the common assumption, the cross-coupled stiffness in the shroud is 2.5 times larger than that in the labyrinth seals. Thus, not only eye-labyrinth seals but also shrouds need to be considered in rotordynamic analysis.
Medication-related harm in older adults following hospital discharge: development and validation of a prediction tool
Authors: Parekh Nikesh , Ali Khalid , Davies John Graham , Stevenson Jennifer M , Banya Winston , Nyangoma Stephen , Schiff Rebekah , van der Cammen Tischa , Harchowal Jatinder , Rajkumar Chakravarthi 
Published: September 2019

ObjectivesTo develop and validate a tool to predict the risk of an older adult experiencing medication-related harm (MRH) requiring healthcare use following hospital discharge.Design, setting, participantsMulticentre, prospective cohort study recruiting older adults (≥65 years) discharged from five UK teaching hospitals between 2013 and 2015.Primary outcome measureParticipants were followed up for 8 weeks in the community by senior pharmacists to identify MRH (adverse drug reactions, harm from non-adherence, harm from medication error). Three data sources provided MRH and healthcare use information: hospital readmissions, primary care use, participant telephone interview. Candidate variables for prognostic modelling were selected using two systematic reviews, the views of patients with MRH and an expert panel of clinicians. Multivariable logistic regression with backward elimination, based on the Akaike Information Criterion, was used to develop the PRIME tool. The tool was internally validated.Results1116 out of 1280 recruited participants completed follow-up (87%). Uncertain MRH cases (‘possible’ and ‘probable’) were excluded, leaving a tool derivation cohort of 818. 119 (15%) participants experienced ‘definite’ MRH requiring healthcare use and 699 participants did not. Modelling resulted in a prediction tool with eight variables measured at hospital discharge: age, gender, antiplatelet drug, sodium level, antidiabetic drug, past adverse drug reaction, number of medicines, living alone. The tool’s discrimination C-statistic was 0.69 (0.66 after validation) and showed good calibration. Decision curve analysis demonstrated the potential value of the tool to guide clinical decision making compared with alternative approaches.ConclusionsThe PRIME tool could be used to identify older patients at high risk of MRH requiring healthcare use following hospital discharge. Prior to clinical use we recommend the tool’s evaluation in other settings.
Radiotherapy mucositis in head and neck cancer: prevention by low-energy surface laser
Authors: Bourbonne Vincent , Otz Joelle , Bensadoun René-Jean , Dissaux Gurvan , Lucia Francois , Leclere Jean-Christophe , Pradier Olivier , Schick Ulrike 
Published: September 2019

BackgroundModern radiotherapy (RT) planning techniques and the use of oral supportive care have reduced the occurrence of acute radiation-induced toxicities. Oral mucositis remains a major concern in patients with head and neck cancer as it can compromise treatment compliance and outcome.ObjectiveTo report the rate of mucositis with the preventive use of surface low-level laser therapy in patients with head and neck cancer.MethodsForty patients treated with definitive (n=27) or adjuvant (n=13) RT using volumetric arc therapy between August 2014 and October 2015 for squamous cell carcinoma of the head and neck were included. All patients were treated using photobiomodulation using surface low-level laser therapy (Heltschl kind FL 3500, 350 mW), 3 times a week during the whole treatment course. The grade of mucositis was obtained from week 1 to week 7 and at 1 month.ResultsThe median RT dose was 70 Gy (64–70). Concomitant chemotherapy was administered in 29 patients. According to the Common Terminology Criteria for Adverse Events (CTCAE) v. 3, grade 0, 1, 2 and 3 mucositis was observed in 9 (22.5%), 9 (22.5%), 16 (40%) and 6 (15%) patients at week 7, and 32 (80%), 2 (5%), 3 (7.5%) and 3 (7.5%) patients at 1 month following treatment. No grade 4 occurred. Median average and maximum dose to the oral mucosa was 42 Gy (12.9–66.3) and 66.6 Gy (39–76), respectively.ConclusionDespite a substantial dose to the oral mucosa, the rate of acute radiation-induced mucositis of grade ≥3 remains low in patients receiving extraoral low-energy laser during RT.
Systematic literature review informing the 2018 update of the EULAR recommendation for the management of large vessel vasculitis: focus on giant cell arteritis
Authors: Monti Sara , Águeda Ana F , Luqmani Raashid Ahmed , Buttgereit Frank , Cid Maria , Dejaco Christian , Mahr Alfred , Ponte Cristina , Salvarani Carlo , Schmidt Wolfgang , Hellmich Bernhard 
Published: September 2019

ObjectivesTo analyse the current evidence for the management of large vessel vasculitis (LVV) to inform the 2018 update of the EULAR recommendations.MethodsTwo systematic literature reviews (SLRs) dealing with diagnosis/monitoring and treatment strategies for LVV, respectively, were performed. Medline, Embase and Cochrane databases were searched from inception to 31 December 2017. Evidence on imaging was excluded as recently published in dedicated EULAR recommendations. This paper focuses on the data relevant to giant cell arteritis (GCA).ResultsWe identified 287 eligible articles (122 studies focused on diagnosis/monitoring, 165 on treatment). The implementation of a fast-track approach to diagnosis significantly lowers the risk of permanent visual loss compared with historical cohorts (level of evidence, LoE 2b). Reliable diagnostic or prognostic biomarkers for GCA are still not available (LoE 3b).The SLR confirms the efficacy of prompt initiation of glucocorticoids (GC). There is no high-quality evidence on the most appropriate starting dose, route of administration, tapering and duration of GC (LoE 4). Patients with GCA are at increased risk of dose-dependent GC-related adverse events (LoE 3b). The addition of methotrexate or tocilizumab reduces relapse rates and GC requirements (LoE 1b). There is no consistent evidence that initiating antiplatelet agents at diagnosis would prevent future ischaemic events (LoE 2a). There is little evidence to guide monitoring of patients with GCA.ConclusionsResults from two SLRs identified novel evidence on the management of GCA to guide the 2018 update of the EULAR recommendations on the management of LVV.
Twist-3 contributions to $$\gamma \gamma \rightarrow \pi ^+\pi ^-,K^+K^-$$ processes in perturbative QCD approach
Authors: Wang Cong , He Jun-Kang , Zhou Ming-Zhen 
Published: September 2019

Abstract
As one of the simplest hadronic processes, $$\gamma \gamma \rightarrow M^{+}M^{-}$$γγ→M+M- ($$M=\pi ,K$$M=π,K) could be a good testing ground for our understanding of the perturbative and nonperturbative structure of QCD, and will be studied with high precision at BELLE-II in the near future. In this paper, we revisit these processes with twist-3 corrections in the perturbative QCD approach based on the $$k_{T}$$kT factorization theorem, in which transverse degrees of freedom as well as resummation effects are taken into account. The influence of the distribution amplitudes on the cross sections are discussed in detail. Our work shows that not only the transverse momentum effects but also the twist-3 corrections play a significant role in the processes $$\gamma \gamma \rightarrow M^{+}M^{-}$$γγ→M+M- in the intermediate energy region. Especially in the few GeV region, the twist-3 contributions become dominant in the cross sections. And it is noteworthy that both the twist-3 result of the $$\pi ^{+}\pi ^{-}$$π+π- cross section and that of the $$K^{+}K^{-}$$K+K- cross section agree well with the BELLE and ALEPH measurements. For the pion and kaon angular distributions, there still exist discrepancies between our results and the experimental measurements. Possible reasons for these discrepancies are discussed briefly.
Heavy neutrino searches at future Z-factories
Authors: Ding Jian-Nan , Qin Qin , Yu Fu-Sheng 
Published: September 2019

AbstractWe analyze the capacity of futureZ-factories to search for heavy neutrinos with their mass from 10 to 85 GeV. The heavy neutrinosNare considered to be produced via the process$$e^+e^-\rightarrow Z\rightarrow \nu N$$e+e-→Z→νNand to decay into an electron or muon and two jets. By means of Monte Carlo simulation of such signal events and the Standard Model background events, we obtain the upper bounds on the cross sections$$\sigma (e^+e^-\rightarrow \nu N\rightarrow \nu \ell jj)$$σ(e+e-→νN→νℓjj)given by theZ-factories with integrated luminosities of 0.1, 1 and 10$$\hbox {ab}^{-1}$$ab-1if no signal events are observed. Under the assumption of a minimal extension of the Standard Model in the neutrino sector, we also present the corresponding constraints on the mixing parameters of the heavy neutrinos with the Standard Model leptons, and find they are improved by at least one order compared to current experimental constraints.
Impact of sintering temperatures on conduction behaviors of ZnO nanoparticles- and MnO-doped SnO2-based thick film varistors obtained by screen printing
Authors: Sendi Rabab 
Published: September 2019

In this study, ZnO nanoparticles and MnO-doped SnO2-based thick film varistors (TFVs) were fabricated using screen printing technique. The sintering temperature had significant impact on the SZM-based TFVs, especially in terms of grain growth, even at a low sintering temperature of 1100[Formula: see text]C. The strong solid-state reaction during sintering may be attributed to the large surface area of the 20 nm ZnO nanoparticles that promoted strong surface reaction even at low sintering temperatures. Moreover, the X-ray diffraction lattice constant and full wave at half maximum data indicated that the sintering process also improved the grain crystallinity with the decrease in intrinsic compressive stress. The sintering temperatures also significantly influenced the electrical properties of the SZM-based TFVs with a significant decrease in the breakdown field from 360 V/mm (sample at 1100[Formula: see text]C) to 158 V/mm (sample at 1250[Formula: see text]C). The grain boundary resistance ([Formula: see text] also experienced a dramatic drop from 266.4 k[Formula: see text] (sample at 1100[Formula: see text]C) to 89.46 k[Formula: see text] (sample at 1250[Formula: see text]C). The sample sintered at 1200[Formula: see text]C exhibited superior electrical behaviors with a nonlinear exponent of 61 and leakage current of 115 [Formula: see text]A. Furthermore, it achieved high permittivity and low dissipation factor at the low frequency range. The conduction behaviors of [Formula: see text] ions with activation energy of approximately 0.6 eV was dominated by decreasing [Formula: see text] and [Formula: see text] defects (around 0.4 eV) with increasing sintering temperature. Therefore, the sintering process can be applied to control the conduction behaviors of SZM-based TFVs doped with ZnO nanoparticle powder and achieve improved structural and electrical properties with good nonlinear behaviors.
Circulating Tumor Cell-Neutrophil Tango along the Metastatic Process
Authors: Saini Massimo , Szczerba Barbara M. , Aceto Nicola 
Published: September 2019

Abstract
The crosstalk between cancer cells and the immune system is crucial for disease progression and its therapeutic targeting is providing exciting results, in particular with newly developed immune checkpoint inhibitors. Current approaches primarily focus on cellular interactions occurring between tumor cells and T lymphocytes; however, recent data highlight a crucial role of neutrophils in support of tumor progression and suggest yet unexplored treatment opportunities. In this review, we summarize the current understanding of those interactions that occur between neutrophils and cancer cells, focusing on both protumor and antitumor activities of neutrophils at different stages of cancer progression. These include infiltration of neutrophils into the primary tumor, their interactions with circulating tumor cells (CTC) within the bloodstream, and their involvement in the establishment of a metastatic niche. Additionally, we discuss how further investigation of CTCs and their interacting immune cell partners may point towards novel immune checkpoint inhibition strategies and provide new insights on the efficacy of already existing immunotherapies.
Bioactivation of Napabucasin Triggers Reactive Oxygen Species–Mediated Cancer Cell Death
Authors: Froeling Fieke E.M. , Swamynathan Manojit Mosur , Deschênes Astrid , Chio Iok In Christine , Brosnan Erin , Yao Melissa A. , Alagesan Priya , Lucito Matthew , Li Juying , Chang An-Yun , Trotman Lloyd C. , Belleau Pascal , Park Youngkyu , Rogoff Harry A. , Watson James D. , Tuveson David A. 
Published: September 2019

Abstract

Purpose:
Napabucasin (2-acetylfuro-1,4-naphthoquinone or BBI-608) is a small molecule currently being clinically evaluated in various cancer types. It has mostly been recognized for its ability to inhibit STAT3 signaling. However, based on its chemical structure, we hypothesized that napabucasin is a substrate for intracellular oxidoreductases and therefore may exert its anticancer effect through redox cycling, resulting in reactive oxygen species (ROS) production and cell death.

Experimental Design:
Binding of napabucasin to NAD(P)H:quinone oxidoreductase-1 (NQO1), and other oxidoreductases, was measured. Pancreatic cancer cell lines were treated with napabucasin, and cell survival, ROS generation, DNA damage, transcriptomic changes, and alterations in STAT3 activation were assayed in vitro and in vivo. Genetic knockout or pharmacologic inhibition with dicoumarol was used to evaluate the dependency on NQO1.

Results:
Napabucasin was found to bind with high affinity to NQO1 and to a lesser degree to cytochrome P450 oxidoreductase (POR). Treatment resulted in marked induction of ROS and DNA damage with an NQO1- and ROS-dependent decrease in STAT3 phosphorylation. Differential cytotoxic effects were observed, where NQO1-expressing cells generating cytotoxic levels of ROS at low napabucasin concentrations were more sensitive. Cells with low or no baseline NQO1 expression also produced ROS in response to napabucasin, albeit to a lesser extent, through the one-electron reductase POR.

Conclusions:
Napabucasin is bioactivated by NQO1, and to a lesser degree by POR, resulting in futile redox cycling and ROS generation. The increased ROS levels result in DNA damage and multiple intracellular changes, one of which is a reduction in STAT3 phosphorylation.
Lessons Learned from Deescalation Trials in Favorable Risk HPV-Associated Squamous Cell Head and Neck Cancer–A Perspective on Future Trial Designs
Authors: Ventz Steffen , Trippa Lorenzo , Schoenfeld Jonathan D. 
Published: September 2019

Abstract
In recent years several clinical studies have investigated deintensified treatments in human papillomavirus (HPV)-associated head and neck squamous cell carcinoma. Two large phase III trials, RTOG 1016 and De-ESCALaTE, which attempted to reduce toxicity by replacing radiotherapy in combination with cisplatin with the use of cetuximab in combination with radiotherapy, recently suggested that radiotherapy + cetuximab leads to inferior survival compared with standard therapy (observed HRs of 1.45 and 5 in RTOG 1016 and De-ESCALaTE), as well as increased rates of locoregional failure. These unexpected results should prompt a careful examination of deintensification trials, both in HPV-associated oropharyngeal cancer and in other contexts. Statistical designs for deintensification studies should be consistent with the study aims of reducing toxicities while maintaining survival nearly identical to the standard of care. We suggest criteria to design future deintensification trials and discuss important operating characteristics, including tradeoffs between power and stringent early stopping rules to reduce the number of patients exposed to inferior treatments. Using retrospective analyses of previous clinical studies, we compared designs with different operating characteristics. As an example, using outcomes data from RTOG 1016 and De-ESCALaTE, we conducted analyses to determine advantages of (i) stringent futility early-stopping rules and of (ii) study designs that leverage both toxicity and efficacy endpoints for interim analyses. We show that increasing the frequency of interim-futility analyses has little impact on power, but the average study duration and number of subjects enrolled before the trial is closed for inferiority can decrease substantially (from 57.8 to 18 months, and from 764 to 645 subjects). Moreover, the number of observed deaths during the study can be reduced by up to 68%.
Dilution of Molecular–Pathologic Gene Signatures by Medically Associated Factors Might Prevent Prediction of Resection Status After Debulking Surgery in Patients With Advanced Ovarian Cancer
Authors: Heitz Florian , Kommoss Stefan , Tourani Roshan , Grandelis Anthony , Uppendahl Locke , Aliferis Constantin , Burges Alexander , Wang Chen , Canzler Ulrich , Wang Jinhua , Belau Antje , Prader Sonia , Hanker Lars , Ma Sisi , Ataseven Beyhan , Hilpert Felix , Schneider Stephanie , Sehouli Jalid , Kimmig Rainer , Kurzeder Christian , Schmalfeldt Barbara , Braicu Elena I. , Harter Philipp , Dowdy Sean C. , Winterhoff Boris J. , Pfisterer Jacobus , du Bois Andreas 
Published: September 2019

Abstract

Purpose:
Predicting surgical outcome could improve individualizing treatment strategies for patients with advanced ovarian cancer. It has been suggested earlier that gene expression signatures (GES) might harbor the potential to predict surgical outcome.

Experimental Design:
Data derived from high-grade serous tumor tissue of FIGO stage IIIC/IV patients of AGO-OVAR11 trial were used to generate a transcriptome profiling. Previously identified molecular signatures were tested. A theoretical model was implemented to evaluate the impact of medically associated factors for residual disease (RD) on the performance of GES that predicts RD status.

Results:
A total of 266 patients met inclusion criteria, of those, 39.1% underwent complete resection. Previously reported GES did not predict RD in this cohort. Similarly, The Cancer Genome Atlas molecular subtypes, an independent de novo signature and the total gene expression dataset using all 21,000 genes were not able to predict RD status. Medical reasons for RD were identified as potential limiting factors that impact the ability to use GES to predict RD. In a center with high complete resection rates, a GES which would perfectly predict tumor biological RD would have a performance of only AUC 0.83, due to reasons other than tumor biology.

Conclusions:
Previously identified GES cannot be generalized. Medically associated factors for RD may be the main obstacle to predict surgical outcome in an all-comer population of patients with advanced ovarian cancer. If biomarkers derived from tumor tissue are used to predict outcome of patients with cancer, selection bias should be focused on to prevent overestimation of the power of such a biomarker.
See related commentary by Handley and Sood, p. 9