bluuebunny/crossref_metadata_2025 huggingface dataset:
The application of S-series ILS specifications data model in civil aircraft customer service system
Authors: Feng Yunwen , Chen Junyu , Lu Cheng , Xue Xiaofeng
Published: August 2021

Civil aircraft customer service is the full support of the main manufacturer from the perspective of customer needs, aircraft performance, and the interests of related parties during the product life cycle. Its data model can coordinate business and data between stakeholders, and provide a framework for business information representation and operation for customer data integration. In order to enable civil aircraft customer service to improve customer satisfaction and meet the development needs of the civil aircraft industry, it is necessary to establish a complete customer service system and form a common customer service business data model. Firstly, the S-series of integrated logistic support(ILS) specifications and ISO 10303-239 PLCS are interpreted to explore the ILS business interface relevance between international specifications. Then, the tools used to establish the customer service business model and data interaction of civil aircraft are sorted out, and how to use them is explained. Finally, the system is constructed from the three levels of civil aircraft customer service requirements, indicators and activities, combined with model tools to build a civil aircraft customer service business data model based on the S-series ILS specifications. This paper provides guidance for realizing the data circulation of various business links of customer service, and provides a basis and method for ensuring the safe operation of aircraft, reducing user operating costs and promoting customer service levels.
Research on the forward flight performance of rotor based on variable-droop leading edge
Authors: Li Congcong , SHI Yongjie , Xu Guohua , Liu Xingliang
Published: August 2021

Aiming at the dynamic stall phenomenon of the retreating side of the rotor in forward flight, the existing flow control method of dynamic leading edge droop was applied to the flow control of forward-flying rotor at three-dimensional scale. A numerical simulation method based on variable droop leading edge is established in this paper. The seesaw rotor is taken as the research object, the moving overset mesh method and RBF grid deformation technology are used, the integral form of Reynolds average N-S equation is the main control equation. The influence of the dynamic leading edge at r/R=0.75~1 on the aerodynamic characteristics of the rotor when the forward ratio is 0.3 is investigated. It is found that variable droop leading edge on the retreating side can effectively inhibit the generation and development of separation vortices near the trailing edge, and has a significant effect on lifting lift coefficient and section normal force coefficient, reducing torque coefficient, and thus improving the equivalent lift-drag ratio of the rotor. In a certain range, the control effect is better with the increase of the droop amplitude under the leading edge.
Conception, réalisation, mise en service du captage et dépoussiérage secondaire de l'aciérie de Dunkerque
Authors: Jager J. M. , Guichard P. , Thoral R. , Rose W. , Dehoux Ph.
Published: August 2021

Trois phases ont contribué au dimensionnement de l'installation de captage-dépoussiérage secondaire des convertisseurs de Sollac Dunkerque : les mesures du Leces sur site, la simulation sur maquette hydraulique, les calculs thermiques et aérauliques.

Le filtre à manches à dépression, en amont de trois ventilateurs, a une capacité de 3 128 000 m3/h à 130 °C. Le montage des équipements, de décembre 1992 à janvier 1993, s'est réalisé dans une aciérie en exploitation.
Nitrogen control in liquid steel for slab casting
Authors: van der Knoop W. , Moonen W. H. L. , Post J. , van Unen G.
Published: August 2021

For the production of a two piece can (DWI), a continuous aonealed material for tin plate is preferred witb a low nitrogen content.

At Hoogovens BOS No. 2, a steelmaking practice has been developed for the entire route to obtain N < 20 ppm. Major features are the blowing techniques to obtain low nitrogen in the BOF, prevention of -pick up during ladle treatrnent and improved shrouding at the caster.
Modélisation thermomécanique des produits longs de coulée continue. Application à la maîtrise de la santé interne par réduction douce
Authors: Do Thong P. , Jolivet J. M. , Lopes C. , Gratacos P. , Roquet J. , Selaries J.
Published: August 2021

La technique de réduction douce est un moyen de maîtriser la qualité interne des produits de coulée continue. L'Irsid a mené des calculs thermomécaniques pour modéliser ce procédé dans le cas particulier de la coulée continue de rond. L'étude a consisté à étudier l'influence de la technologie de réduction (2 ou 4 génératrices), du format et de la nuance sur la mise en compression du pâteux et sur les efforts à mettre en œuvre

Il ressort de cette étude que la technologie de réduction sur 2 génératrices minimise les efforts à appliquer pour une même efficacité de compression.
Symmetric and asymmetric shocked gas jets for laser-plasma experiments
Authors: Rovige L. , Huijts J. , Vernier A. , Andriyash I. , Sylla F. , Tomkus V. , Girdauskas V. , Raciukaitis G. , Dudutis J. , Stankevic V. , Gecys P. , Faure J.
Published: August 2021

Shocks in supersonic flows offer both high density and sharp density gradients that are used, for instance, for gradient injection in laser-plasma accelerators. We report on a parametric study of oblique shocks created by inserting a straight axisymmetric section at the end of a supersonic “de Laval” nozzle. The effect of different parameters, such as the throat diameter and straight section length on the shock position and density, is studied through computational fluid dynamics (CFD) simulations. Experimental characterizations of a shocked nozzle are compared to CFD simulations and found to be in good agreement. We then introduce a newly designed asymmetric shocked gas jet, where the straight section is only present on one lateral side of the nozzle, thus providing a gas profile well adapted for density transition injection. In this case, full-3D fluid simulations and experimental measurements are compared and show excellent agreement.
Development of solid state terahertz interferometer for the first plasma on HL-2M tokamak
Authors: Shi P. W. , Yang Z. C. , Shi Z. B. , Xu L. F. , Deng W. C. , Jiang M. , Chen W. , Zhong W. L. , Wen J. , Fang K. R. , Tong R. H. , Xue G. Q. , Yu X. , Li Y. G. , Ji X. Q. , Zhang Y. P. , Yang Q. W. , Xu M. , Wang Z. X. , Duan X. R.
Published: August 2021

A solid state terahertz interferometer has been developed on the recent commissioned HL-2M tokamak. It can work in a wide frequency region of 220–325 GHz, and the terahertz wave is generated from a low frequency phase locked voltage controlled oscillator with the frequency multiplying technique. A phase processor based on field programmable gate array (FPGA) technology is designed for the heterodyne interferometer, and it contributes to real-time display of electron density. To extract phase information, a novel numerical algorithm related to fast Fourier transform is written on the FPGA chip and enables one to obtain phase shift without being affected by amplitude variation induced by plasma absorption or frequency modulation from the outer electromagnetic environment. The interferometer achieves minimum measurable electron density in the order of 1016 m−3. With the plasma diagnosis, electron density and low frequency tearing mode have been measured during the first experimental campaign.
Magnetic interactions and spin excitations in van der Waals ferromagnet

VI3
Authors: Gordon Elijah , Mkhitaryan V V , Zhao Haijun , Lee Y , Ke Liqin
Published: August 2021

Using a combination of density functional theory (DFT) and spin-wave theory methods, we investigate the magnetic interactions and spin excitations in semiconducting VI3. Exchange parameters of monolayer, bilayer, and bulk forms are evaluated by mapping the magnetic energies of various spin configurations, calculated using DFT+U, onto the Heisenberg model. The intralayer couplings remain largely unchanged in three forms of VI3, while the interlayer couplings show stronger dependence on the dimensionality of the materials. We calculate the spin-wave spectra within a linear spin-wave theory and discuss how various exchange parameters affect the magnon bands. The magnon–magnon interaction is further incorporated, and the Curie temperature is estimated using a self-consistently renormalized spin-wave theory. To understand the roles of constituent atoms on magnetocrystalline anisotropy energy (MAE), we resolve MAE into sublattices and find that a strong negative V-I inter-sublattice contribution is responsible for the relatively small easy-axis MAE in VI3.
Applied ecoimmunology: using immunological tools to improve conservation efforts in a changing world
Authors: Ohmer Michel E B , Costantini David , Czirják Gábor Á , Downs Cynthia J , Ferguson Laura V , Flies Andy , Franklin Craig E , Kayigwe Ahab N , Knutie Sarah , Richards-Zawacki Corinne L , Cramp Rebecca L
Published: August 2021

Ecoimmunology is a rapidly developing field that explores how the environment shapes immune function, which in turn influences host–parasite relationships and disease outcomes. Host immune defence is a key fitness determinant because it underlies the capacity of animals to resist or tolerate potential infections. Importantly, immune function can be suppressed, depressed, reconfigured or stimulated by exposure to rapidly changing environmental drivers like temperature, pollutants and food availability. Thus, hosts may experience trade-offs resulting from altered investment in immune function under environmental stressors. As such, approaches in ecoimmunology can provide powerful tools to assist in the conservation of wildlife. Here, we provide case studies that explore the diverse ways that ecoimmunology can inform and advance conservation efforts, from understanding how Galapagos finches will fare with introduced parasites, to using methods from human oncology to design vaccines against a transmissible cancer in Tasmanian devils. In addition, we discuss the future of ecoimmunology and present 10 questions that can help guide this emerging field to better inform conservation decisions and biodiversity protection. From better linking changes in immune function to disease outcomes under different environmental conditions, to understanding how individual variation contributes to disease dynamics in wild populations, there is immense potential for ecoimmunology to inform the conservation of imperilled hosts in the face of new and re-emerging pathogens, in addition to improving the detection and management of emerging potential zoonoses.
Theoretical viscoelastic deformations due to an expansion source in a spherical earth model
Authors: Sun Wenke , Tang He
Published: August 2021

Sources of expansion, such as nuclear explosions and magma chambers, can cause various surface effects, such as displacement and gravity field change on the Earth. The deformation simulation of an expansion source can be traced back to certain classic works nearly 70 yr ago, which were primarily based on a half-space earth model. However, the deformation of expansion sources in a spherical earth model has not been presented in the context of the semi-analytical viscoelastic Love numbers framework. In this study, we present the deformation Green's function for an expansion source in a spherical, non-rotating, viscoelastic, isotropic layered earth model using a semi-analytical method. We further obtain the analytical Green's functions for an elastic model in the near field. In addition, the influence of the stratification, curvature, and viscosity on the deformation is analysed using a layered spherical earth model. The suitability and effectiveness of the formulas are verified by numerical experiments and compared with previous results. The method presented in this paper is useful for explaining the viscoelastic deformations caused by the deep expansion source, for example, large magma chambers and upwelling of a mantle plume, in the layered viscoelastic earth model.
Social Emotions and the Legitimation of the Fertility Technology Market
Authors: Mimoun Laetitia , Trujillo-Torres Lez , Sobande Francesca
Published: August 2021

Using the sociology of emotions, we investigate the role of social emotions as a legitimating force in the market. In a longitudinal study of the media coverage surrounding US fertility technologies, we find that legitimation involves the establishment of hierarchies among feeling rules, which dictate what social emotions are expressed toward markets, consumers, and technologies. We delineate three mechanisms (polarizing, reifying, and transforming social emotions) that are affected by trigger events such as product innovations and historical developments. These mechanisms work to (re)shape regulatory, normative, and cultural-cognitive legitimacy pillars, influencing the overall cultural attention paid to a market. Consequently, legitimation is ongoing and fragmented as the dominance of feeling rules varies across multiple entities and over time, with negative social emotions and controversies at times aiding this process rather than exclusively hindering it.
Dust growth, fragmentation, and self-induced dust traps in phantom
Authors: Vericel Arnaud , Gonzalez Jean-François , Price Daniel J , Laibe Guillaume , Pinte Christophe
Published: August 2021

We present the implementation of a dust growth and fragmentation module in the public smoothed particle hydrodynamics (SPH) code phantom. This module is made available for public use with this paper. The coagulation model considers locally monodisperse dust size distributions around single values that are carried by the SPH particles. Along with the presentation of the model, implementation, and tests, we showcase growth and fragmentation in a few typical circumstellar disc simulations and revisit previous results. The module is also interfaced with the radiative transfer code mcfost, which facilitates the comparison between simulations and ALMA observations by generating synthetic maps. Circumstellar disc simulations with growth and fragmentation reproduce the ‘self-induced dust trap’ mechanism first proposed in 2017, which supports its existence. Synthetic images of discs featuring this mechanism suggest it would be detectable by ALMA as a bright axisymmetric ring at several tens of au from the star. With this paper, our aim is to provide a public tool to be able to study and explore dust growth in a variety of applications related to planet formation.
Dynamical properties ofz∼4.5 dusty star-forming galaxies and their connection with local early-type galaxies
Authors: Rizzo Francesca , Vegetti Simona , Fraternali Filippo , Stacey Hannah R , Powell Devon
Published: August 2021

There is a large consensus that gas in high-z galaxies is highly turbulent, because of a combination of stellar feedback processes and gravitational instabilities driven by mergers and gas accretion. In this paper, we present the analysis of a sample of five Dusty Star Forming Galaxies (DSFGs) at 4 ≲ z ≲ 5. Taking advantage of the magnifying power of strong gravitational lensing, we quantified their kinematic and dynamical properties from ALMA observations of their [C ii] emission line. We combined the dynamical measurements obtained for these galaxies with those obtained from previous studies to build the largest sample of z ∼ 4.5 galaxies with high-quality data and sub-kpc spatial resolutions, so far. We found that all galaxies in the sample are dynamically cold, with rotation-to-random motion ratios, V/σ, between 7 and 15. The relation between their velocity dispersions and their star formation rates indicates that stellar feedback is sufficient to sustain the turbulence within these galaxies and no further mechanisms are needed. In addition, we performed a rotation curve decomposition to infer the relative contribution of the baryonic (gas, stars) and dark matter components to the total gravitational potentials. This analysis allowed us to compare the structural properties of the studied DSFGs with those of their descendants, the local early type galaxies. In particular, we found that five out of six galaxies of the sample show the dynamical signature of a bulge, indicating that the spheroidal component is already in place at z ∼ 4.5.
WALLABY Pre-Pilot Survey: the effects of angular momentum and environment on the H i gas and star formation properties of galaxies in the Eridanus supergroup
Authors: Murugeshan C , Kilborn V A , For B-Q , Wong O I , Wang J , Westmeier T , Stevens A R H , Spekkens K , Kamphuis P , Staveley-Smith L , Lee-Waddell K , Kleiner D , Koribalski B S , Cluver M E , Oh S-H , Rhee J , Catinella B , Reynolds T N , Dénes H , Elagali A
Published: August 2021

We use high-resolution ASKAP observations of galaxies in the Eridanus supergroup to study their H i, angular momentum, and star formation properties, as part of the WALLABY pre-pilot survey efforts. The Eridanus supergroup is composed of three sub-groups in the process of merging to form a cluster. The main focus of this study is the Eridanus (or NGC 1395) sub-group. The baryonic specific angular momentum – baryonic mass (jb−Mb) relation for the Eridanus galaxies is observed to be an unbroken power law of the form $j_{\mathrm{b}} \propto M_{\mathrm{b}}^{0.57 \pm 0.05}$, with a scatter of ∼0.10 ± 0.01 dex, consistent with previous works. We examine the relation between the atomic gas fraction, fatm, and the integrated atomic disc stability parameter q (the fatm−q relation), and find that the Eridanus galaxies deviate significantly from the relation owing to environmental processes such as tidal interactions and ram pressure affecting their H i gas. We find that a majority of the Eridanus galaxies are H i deficient compared to normal star-forming galaxies in the field. We also find that the star formation among the Eridanus galaxies may be suppressed owing to their environment, thus hinting at significant levels of pre-processing within the Eridanus sub-group, even before the galaxies have entered a cluster-like environment.
BSCI-01. Small RNAseq analysis of microRNAs in brain metastasis
Authors: Jancalek Radim , Siegl Frantisek , Sana Jiri , Sidorova Simona , Vecera Marek , Trachtova Karolina , Hendrych Michal , Vybihal Vaclav , Smrcka Martin , Hermanova Marketa , Kazda Tomas , Slaby Ondrej
Published: August 2021

MicroRNAs (miRNAs) are a well-known subclass of short non-coding RNAs responsible for posttranscriptional gene silencing and have been described as dysregulated in many cancers. They have also been shown to be both specific diagnostic, prognostic, and predictive biomarkers as well as therapeutic targets. Therefore, specific miRNA expression patterns of BMs of various origins could serve as a promising diagnostic tool for determining both the original tumor and the prognosis in patients with BMs of unknown origin.

For identifying significantly dysregulated miRNAs among BMs (n = 90) with various origin and non-tumor brain tissues (n = 12), small RNAseq analyses were used. cDNA libraries were prepared using QIAseq miRNA Library Kit and purified by Qiaseq beads. The final sequencing analyses were performed by Next 500/550 High Output v2 Kit-75 cycles using the NextSeq 500 instrument. For miRNA mapping and analysis, Miraligner and MirBase were used.

Bioinformatic analysis of obtained sequencing data identified 472 significantly dysregulated miRNAs (logFc>2, adj.p-value<0.05) between BM and non-tumor samples. The comparison of BMs origin from lung BMs (n = 26) with other BMs revealed 132 significantly dysregulated miRNAs, mainly miR-4662a-5p, miR-1179, miR-211-5p, miR-146a-5p, and miR-194-5p. The most significantly dysregulated miRNAs in breast BMs were miR-4728-3p, miR-211-5p, miR-184, miR-365b-5p, and miR-2115-3p. In BMs originating from melanoma, miR-200c-3p, miR-141-5p, miR-200b-5p, miR-514a-3p, and miR-200b-3p showed the most aberrant expression.

We have demonstrated that miRNA profiling could be a potent tool for the partition of brain metastases based on their origin. We found that miRNA signatures corresponding to particular origins are rather distinct from the profiles of the rest of BMs. Our results suggest that after validation, miRNA profiling can be used to identify the origin of brain metastases and potentially for the refinement of the diagnosis.

Supported by the Ministry of Health of the Czech Republic, grant nr. NV18-03-00398.
BSCI-04. Tumor-educated platelets promote breast cancer brain metastasis and therapeutic resistance
Authors: Tabet Elie , Tannous Bakhos
Published: August 2021

Platelets have been shown to play an important role in systemic and local tumor modulation. Once encountered by tumor cells, platelets are educated to collect and release pro-tumor factors in the tumor/microenvironment, serving as a guiding partner for metastasis. This educational program, however, is not well understood. Here, we show that tumor-educated platelets (TEPs) acquire tumor promoting functions and drive breast cancer progression, metastasis to distal sites including the brain, as well as therapeutic resistance. Importantly, TEPs promoted an increased pro-tumorigenic effect on metastatic breast cancer, compared to their wild-type counterpart, leading to epithelial to mesenchymal transition through NF-κB/STAT3 signaling axis via C/EBPβ transcription factor. Our findings point to the important role of TEPs in breast cancer brain metastasis and therapeutic resistance, which could have a major implication in other tumor types, endorsing TEPs as a potential therapeutic target.
BSCI-11. Targeting PI3K/Akt/mTOR pathway to prevent melanoma brain metastasis
Authors: Tehranian Cedric , Fankhauser Laura , Harter Patrick N , Ratcliffe Colin D H , Zeiner Pia S , Messmer Julia M , Hoffmann Dirk C , Frey Katharina , Westphal Dana , Ronellenfitsch Michael W , Sahai Erik , Wick Wolfgang , Karreman Matthia A , Winkler Frank
Published: August 2021

Background

Patients developing brain metastasis (BM) still face a poor survival due to limited treatment options. BM prevention using low dose drug schedules could be a more potent strategy with less side effects than treating established BM. This could add a real benefit to the ongoing challenge of facing the frequent BM formation in high-risk malignant melanoma (MM) patients.

Methods

Aiming to study the dynamics of PI3K/Akt/mTOR (PAM) pathway activation during the brain metastatic cascade, in vivo molecular imaging with an Akt biosensor was performed. Long-term intravital multiphoton microscopy through a chronic cranial window in mice was employed to investigate timing and effectiveness of PAM pathway inhibition for BM prevention.

Results

In vivo molecular imaging revealed the activation of PAM pathway as a prerequisite for extravasation of circulating MM cells in the brain. However, established human BM present with heterogeneous activation of the PAM pathway. Moreover, in two MM mouse models, PAM pathway inhibition with the brain-penetrant dual PI3K/mTOR inhibitor GNE-317 resulted in only moderate effects on established BM. In contrast, giving low dose GNE-317 in a preventive schedule successfully reduced growth rate and number of BM in both mouse models. Longitudinal intravital multiphoton microscopy suggests that the first, rate-limiting, steps of BM formation can be effectively targeted by dual PI3K/mTOR inhibition.

Conclusion

PAM pathway activation is key for the critical early steps of MM metastatic brain colonization. These findings reveal that early PAM pathway inhibition is a promising strategy to prevent the formation of clinically relevant BM.
BSCI-13. MTH1 expression is upregulated in brain metastases of malignant melanoma
Authors: Timmer Marco
Published: August 2021

Objective

MuT Homolog1 (MTH1) is an enzyme involved in DNA repair in normal cells and is often up- regulated in cancer cells. The enzyme catalyses the hydrolysis of oxidised dNTPs, to prevent their incorporation into DNA or RNA, resulting in mutations or cell damage/death. Cancer cells can have a high concentration of ROS, due to defective redox regulation. This results in the damage of DNA and oxidises free dNTPS, which in turn leads to mutations in DNA replication or cell death. Identifying MTH1 in brain metastases could present a target for treatment with MTH1-Inhibitors.

Methods

The quantification of MTH1 expression was shown using Western Blot analysis. 16 tumours were obtained during neurosurgery, 8 metastatic and 8 recurrent tumours of the same patient, and immediately frozen using liquid nitrogen. The proteins were extracted using RIPA lysis buffer. Western Blot was performed and detection followed via peroxidase linked secondary antibodies.

Results

MTH1 expression was shown to be up-regulated in brain metastases (1,442+/-0,6374) versus normal brain tissue (0,4133+/-0,277). However, in the recurrent tumour of the brain metastases, MTH1 was not expressed in a significantly higher amount compared the controll tissue and less than in the brain metastases (0,6941+/-0,4146).

Conclusion

The high expression of MTH1 in cerebral metastases is not uncommon for many cancers and thus presents a therapeutic target for MTH1-inhibitors, provided these are able to cross the blood brain barrier. Comparison to the primary melanoma tumour would be useful in showing significant differences of the metastases. Lower levels of MTH1 in recurrent brain metastases may suggest dedifferentiation from the original metastases. It may present a target for specific treatment of brain metastases of melanoma.
BSCI-15. Osteopontin plays a crucial role in invasiveness of triple negative breast cancer cells in the context of human microglia
Authors: Wojnicki Kamil , Kochalska Agata , Poleszak Katarzyna , Roura Adria-Jaume , Matyja Ewa , Czernicki Tomasz , Gieryng Anna , Kaminska Bozena
Published: August 2021

The triple-negative breast cancer (TNBC) is the most malignant among breast cancers and has the high risk of developing metastasis into the brain. Metastases of breast cancers are increasing and pose a clinical challenge as the current treatments are not effective due to the unique brain microenvironment for metastatic breast cancer cells. While the contribution of brain macrophages to the formation of the metastatic niche is established, factors responsible for the crosstalk between cells remain elusive. SPP1 encoding a secreted phosphoprotein 1 (ostepontin) is highly overexpressed in malignant breast cancers. We evaluated the role of SPP1 in invasion and metastasis of human breast cancer cells. We found the increased invasion of triple-negative MDA-MB-231 (MDA-231) cells in the presence of human microglial HMSV40 cells. Using Western blot analysis demonstrated the elevated levels of focal adhesion kinase (FAK) and signal transducer and activator of transcription 3 (STAT3) in MDA-231 cells in co-cultures. Moreover, blocking SPP1 and integrin interactions with the synthetic RGD peptide, efficiently diminished both basic and microglia-induced invasion of MDA-231. To assess the role of SPP1 in cell invasion, we established the MDA-231 cells with knocked-down SPP1 expression using shRNA (shSPP1). Interestingly, the shSPP1 cells were unresponsive towards HMSV40 microglia. We have previously found that an antibiotic minocycline reduces SPP1 expression in glioma cells. We performed cell toxicity studies on 4 breast cancer cell lines and various non-malignant cells. All tested malignant cancer cells were more sensitize to minocycline than non-cancerous cells and breast cancer cells derived from TNBC were the most susceptible. Altogether, we demonstrate that microglia support invasion of breast cancer cells via SPP1/osteopontin triggering the integrin signalling, and minocycline by downregulating SPP1 expression may reduce both basic and microglia-induced cancer invasion. Therefore, we purpose that minocycline could be a new therapeutics targeting metastatic brain cancers.
OTHR-06. PACS Lesion Tracking Tool provides real time automatic information on brain tumor metastasis growth curves and RECIST criteria
Authors: Jang Benjamin , Lin MingDe , Owens Randy , Bousabarah Khaled , Mahajan Amit , Fadel Sandra Abi , Ikuta Ichiro , Tocino Irena , Aboian Mariam
Published: August 2021

Objective

Communicating metastatic brain treatment response can be complicated. A widely used method to assess clinical response is called response evaluation criteria in solid tumors or RECIST. In our study, we use a PACS Lesion Tracking Tool (TT) to assess intracranial metastasis using RECIST criteria. We predict that the TT will be superior to the standard radiology reports.

Methods

Nuance ® mPowerTM was used to identify 30 patients with brain metastasis who received brain MRI from 4/2020–4/2021. Patient’s first brain MRI with metastasis was set as baseline and subsequent 3 brain MRI studies were examined. All lesions were measured on post-gadolinium sequence and defined as target lesions or new lesions. The TT was used to measure lesion size over time with creation of growth curves and RECIST outcomes, which include stable disease, progressive disease, partial response, or complete response. Subsequently, RECIST evaluations were compared with radiologic impressions for discrepancy, and further evaluations were made to see if it made a clinical difference in patient management and/or provide additional useful information. These evaluations were given a rating of agree/yes, equivocal, or disagree/no. They were assessed by 3 neuroradiologists.

Results

Number of lesions ranged from 1–27. The assessments from 3 neuroradiologists were averaged. Comparing impression versus RECIST evaluation, the results demonstrated the following: 8/30 disagreement, 4/30 equivocal, and 18/30 agreement. Using more stringent criteria, assessing whether the TT would result in either change in patient management or provide additional useful information, the results were the following: 6/30 yes, 4/30 equivocal, and 20/30 no.

Discussion

In addition to providing real time RECIST criteria evaluations and visually descriptive lesion growth tables, the TT was easy to use. Interpretation of these additional data provided more clarity and was found to be superior to standard radiology report.
OTHR-07. Systematic Review and Meta-analysis of Lung Cancer Brain Metastasis and Primary Tumor PD-L1 Expression Discordance
Authors: Tonse Raees , Rubens Muni , Appel Haley , Tom Martin C , Hall Matthew D , Odia Yazmin , Mehta Minesh P , McDermott Michael W , Ahluwalia Manmeet S , Kotecha Rupesh
Published: August 2021

Background

Novel immunotherapeutic strategies, such as those targeting the PD-1/PD-L1 axis, are promising in patients with metastatic lung cancer and are often administered when tumors show PD-L1 positivity. The objective of this study was to analyze PD-L1 receptor discordance in tumor cell between the primary tumor and lung cancer brain metastasis (LCBM).

Methods

A systematic review of series published prior to April 2021 obtained from the Medline database of biopsied or resected LCBM evaluating PD-L1 discordance was performed using PRISMA guidelines. Weighted random effects models were used to calculate pooled estimates.

Results

Six full-text articles (n=247 patients) with a median of 32 patients in each study (range: 24–73 patients) reported PD-L1 receptor expression analyses of both primary lung tumors and brain metastases. The majority of patients (81%) were smokers, with 67% non-small cell lung cancer and 33% small cell lung cancer. The pooled estimate for overall PD-LI receptor concordance between primary and LCBM was 76% (95% CI: 52%-90). The positivity rate varied when analyzed by various cutoff levels of PD-L1 expression; for <1% expression, it was 41% (95% CI: 22%-62%) for primary vs. 58% (95% CI: 35%-78%) for LCBM; for PD-L1 expression of 1–50%, it was 24% (95% CI: 13%-40%) vs. 19% (95% CI: 10%-33%); and for PD-L1 >50% it was 12% (95% CI: 4%-33%) vs. 21% (95% CI: 14%-29%) (p=0.425). The pooled estimate for overall PD-LI receptor discordance between primary and LCBM was 17% (95% CI: 10%-27%). Meta-regression analysis showed that age, sex, smoking status, and histology were not associated with PD-LI receptor discordance.

Conclusions

PD-L1 status discordance in tumor cell occurs in approximately 20% of LCBM, with the greatest discordance in the <1% expression category. Awareness of this discordance is important for the selection of immune checkpoint inhibitor therapy as well as in the analysis of patterns of failures.
OTHR-08. Efficacy of anti-epileptic drug prophylaxis on seizure prevention in patients with brain metastases: A systematic review and meta-analysis
Authors: Souders Leslie , Beg Usman , Svetly Conner , Dabrowski Michael , Hamidi Nima , Padmanaban Varun , Mansouri Alireza
Published: August 2021

Introduction

Seizures can occur in patients with brain metastasis and are often debilitating, leading to morbidity, mortality, and economic burden. Implementation of anti-epileptic drugs (AEDs) prophylaxis remains controversial, and provider dependent as current Level III guidelines recommend against their use. This systematic review gathers the current evidence on the effectiveness of AED prophylaxis on preventing new-onset seizures in patients with BM. Associated adverse effects of AED usage in this population are also reported.

Methods

Using PRISMA guidelines, a pertinent search was conducted on Embase, PubMed, and Web of Science to identify journal articles that reported AED prophylaxis as a variable to modify seizure frequency in adult patients with BM. Data of interest included AED agent, new-onset seizure frequency, and safety profile. A meta-analysis was performed to calculate odds ratio using Der-Simonian and Laird methods to compare AED group with control for new seizures. Heterogeneity was determined by Cochran Q test and I2.

Results

Our search returned 175 publications of which 5 retrospective cohort studies met inclusion criteria. A total of 1,292 patients (283 receiving AED prophylaxis, and 1,009 in control group) were included across the studies. AEDs used were phenobarbital, levetiracetam, phenytoin, and valproate. Meta-analysis showed no difference in seizure frequency between the AED and the control group (OR = 0.98; 95%-CI: 0.56–1.72). Heterogeneity: I2 = 7%. Adverse events were not reported in the publications.

Conclusion

Our meta-analysis suggests that there is no improvement in frequency of new seizures with AED prophylaxis in BM patients, supporting current guidelines. However, the evidence is based on a small patient population and retrospective studies. Additional studies are needed to determine efficacy of prophylaxis with newer AEDs and establish guidelines to target therapies for improving morbidity, mortality, and quality of life in patients with BM.
OTHR-12. The development of machine learning algorithms for the differentiation of glioma and brain metastases – a systematic review
Authors: Brim Waverly Rose , Jekel Leon , Petersen Gabriel Cassinelli , Subramanian Harry , Zeevi Tal , Payabvash Sam , Bousabarah Khaled , Lin MingDe , Cui Jin , Brackett Alexandria , Mahajan Ajay , Johnson Michele , Mahajan Amit , Aboian Mariam
Published: August 2021

Purpose

Medical staging, surgical planning, and therapeutic decisions are significantly different for brain metastases versus gliomas. Machine learning (ML) algorithms have been developed to differentiate these pathologies. We performed a systematic review to characterize ML methods and to evaluate their accuracy.

Methods

Studies on the application of machine learning in neuro-oncology were searched in Ovid Embase, Ovid MEDLINE, Cochrane trials (CENTRAL) and Web of science core-collection. A search strategy was designed in compliance with a clinical librarian and confirmed by a second librarian. The search strategy comprised of controlled vocabulary including artificial intelligence, machine learning, deep learning, magnetic resonance imaging, and glioma. The initial search was performed in October 2020 and then updated in February 2021. Candidate articles were screened in Covidence by at least two reviewers each. A bias analysis was conducted in agreement with TRIPOD, a bias assessment tool similar to CLAIM.

Results

Twenty-nine articles were used for data extraction. Four articles specified model development for solitary brain metastases. Classical ML (cML) algorithms represented 85% of models used, while deep learning (DL) accounted for 15%. cML algorithms performed with an average accuracy, sensitivity, and specificity of 82%, 78%, 88%, respectively; DL performed 84%, 79%, 81%. The support vector machine (SVM) algorithm was the most common used cML model in the literature and convolutional neural networks (CNN) were standard for DL models. We also found T1, T1 post-gadolinium and T2 sequences were most commonly used for feature extraction. Preliminary TRIPOD analysis yielded an average score of 14.25 (range 8–18).

Conclusion

ML algorithms that can accurately classify glioma from brain metastases have been developed. SVM and CNN are leading approaches with high accuracy. Standardized algorithm performance reporting is a clear limitation to be addressed in future studies.
RADI-01. Cystic brain metastases managed with reservoir placement and stereotactic radiosurgery
Authors: Park David , Schulder Michael
Published: August 2021

Background

Stereotactic radiosurgery (SRS) has become a mainstay of treatment for patients with metastatic brain tumors. However, metastatic tumors with a large cystic component often exceed the size limit for safe and effective SRS. In such cases, surgical resection may not be the preferred first method of treatment, due to tumor location, patient co-morbidities, and patient preference. In such cases volume reduction by cyst aspiration followed by SRS may be a preferred option.

Methods

Seven patients were treated with this method. We performed reservoir insertion for the aspiration of cystic component in each patient and followed that with outpatient SRS.

Results

Mean overall volume reduction from this treatment method was 80% (range 46.5–94.9). Mean volume reduction from the cyst aspiration alone was 60.7% (range 3.5–90.9), and after SRS a further 71.6% (range 34.6–94.4), accounting for some cyst reaccumulation between the time of surgery and SRS. The interval between those two procedures were 24 days on average (range 11–58 days). Repeat reservoir aspiration was done a total of 10 times in 5 patients.

Conclusion

Cyst aspiration with reservoir placement followed by SRS is a good option for patients with large cystic brain metastases. The reservoir allows for repeat aspiration if needed. Catheter placement at the center of the cyst, and SRS within 2–3 weeks of surgery, can maximize the likelihood of a successful outcome.
RADI-13. Systemic Therapy Type and Timing Effects on Radiation Necrosis Risk in HER2+ Breast Cancer Brain Metastases Patients Treated with Stereotactic Radiosurgery
Authors: Park Christine , Buckley Evan , Van Swearingen Amanda , Giles Will , Herndon James , Floyd Scott , Anders Carey
Published: August 2021

Background

Current standard of care options for HER2+ breast cancer brain metastasis (BCBrM) include radiation therapy, brain permeable systemic therapies, and in select cases, neurosurgical resection. There is a concern that HER2-directed systemic therapies when administered concurrently with stereotactic radiosurgery (SRS) may increase the risk of radiation necrosis (RN). This study explores the impact of timing and type of systemic therapies on the development of RN in patients treated with SRS for HER2+ BCBrM.

Methods

This was a single-institution, retrospective study including patients ≥18 years of age with HER2+ BCBrM who received SRS between 2013 and 2018 with at least 12-month post-SRS follow-up. Presence of RN was determined at one-year post-SRS. Demographics, radiotherapy parameters, and timing (“during” defined as four weeks before/after SRS) and type of systemic therapy were evaluated.

Results

Among 46 patients with HER2+ BCBrM who received SRS, 28 (60.9%) developed RN and 18 (39.1%) did not. Age (mean 53.3 vs 50.4 years, respectively), radiotherapy parameters (dose, fraction, CTV, GTV, CI, V12Gy, all p>0.05), and receipt of any type of systemic therapy during SRS (60.7% vs 55.6%, p = 0.97) did not differ between patients who did or did not develop RN. However, patients who developed RN more commonly received more than one line of HER2-directed therapy independent of SRS timing compared to those who did not develop RN (75.0% vs 44.4%, p = 0.08). In fact, a significantly higher proportion of those who developed RN received more than one line of HER2-directed therapy during a given SRS treatment compared to those did not develop RN (35.7% vs 5.6%, p<0.05).

Conclusions

Patients with HER2+ BCBrM who receive multiple lines of HER2-directed therapy during SRS for BCBrM may be at higher risk of RN. Collectively, this data supports a practice of holding HER2-directed therapy during treatment with SRS if medically acceptable.
RADI-17. Outcomes for patients with triple negative breast cancer treated with upfront stereotactic radiosurgery for brain metastases
Authors: An Ran , Wang Yan , Wang Fuchenchu , Raghavendra Akshara Singareeka , Gao Chao , Amaya Diana N , Ibrahim Nuhad K , Li Jing
Published: August 2021

Background

Triple-negative breast cancer (TNBC) is an aggressive subtype with high propensity of developing brain metastases (BM). Clinical outcomes and prognostic factors after stereotactic radiosurgery (SRS) for BM were not well defined.

Methods

We identified 57 consecutive TNBC patients (pts) treated with single fraction SRS for BM during 05/2008–04/2018. Overall survival (OS) from BM diagnosis and freedom from BM progression (FFBMP) after initial SRS were evaluated. BM progression was defined as local and/or distant brain failure (LBF, DBF) after SRS. Kaplan-Meier analyses and Cox proportional hazard regression were used to estimate survival outcomes and identify prognostic factors.

Results

The median time to BM development from TNBC diagnosis was 23.7 months (mo) (range 0.7‒271.1). Median OS was 13.1 mo (95%CI 8.0‒19.5). On univariate analysis, Karnofsky performance score (KPS) >70 (p=0.03), number of BMs <3 (p=0.016), and BM among the first metastatic sites (p=0.04) were associated with longer OS. On multivariate analysis, KPS ≤70 was associated with higher risk of death (HR 3.0, p=0.03). Of 46 pts with adequate imaging follow-up, 29 (63%) had intracranial progression with a median FFBMP of 7.4 mo (95% CI 5.7–12.7). At 12 mo the estimated cumulative DBF rate was 61.1% (95%CI 40.8%–74.4%) and LBF rate was 17.8% (95%CI 2%–31.1%). Number of BMs (≥3 vs <3) was not associated with FFBMP (p=0.7). Of the 29 pts with BM progression, additional radiation therapy (RT) (vs. no RT) was associated with improved survival (21.7 vs. 7.0 mo, p<0.0001).

Conclusions

TNBC pts with BM treated with SRS had an OS of 13.1 mo and FFBMP of 7.4 mo. Good KPS was an independent prognostic factor for OS. Further studies with more pts or conducted prospectively are needed to better understand and to improve treatment outcomes in this pt population.
SURG-03. The effect of surgery on radiation necrosis in irradiated brain metastases: extent of resection and long-term clinical and radiographic outcomes
Authors: Newman William , Goldberg Jacob , Guadix Sergio , Brown Samantha , Reiner Anne , Beal Kathryn , Brennan Cameron , Tabar Viviane , Young Robert , Moss Nelson
Published: August 2021

Objective

Radiation therapy is a cornerstone of brain metastasis (BrM) management but carries the risk of radiation necrosis (RN), which can require resection for palliation or diagnosis. We sought to determine the relationship between extent of resection (EOR) of pathologically-confirmed RN and postoperative radiographic and symptomatic outcomes.

Methods

A single-center retrospective review was performed at an NCI-designated Comprehensive Cancer Center to identify all surgically-resected, previously-irradiated necrotic BrM without admixed recurrent malignancy from 2003–2018. Clinical, pathologic and radiographic parameters were collected. Volumetric analysis determined EOR and longitudinally evaluated perilesional T2-FLAIR signal preoperatively, postoperatively, and at 3-, 6-, 12-, and 24-months postoperatively when available. Rates of time to 50% T2-FLAIR reduction was calculated using cumulative incidence in the competing risks setting with last follow-up and death as competing events. The Spearman method was used to calculate correlation coefficients, and continuous variables for T2-FLAIR signal change, including EOR, were compared across groups.

Results

Forty-six patients were included. Most underwent prior stereotactic radiosurgery with or without whole-brain irradiation (n=42, 91%). Twenty-seven operations resulted in gross-total resection (59%; GTR). For the full cohort, T2-FLAIR edema decreased by a mean of 78% by 6 months postoperatively that was durable to last follow-up (p<0.05). EOR correlated with edema reduction at last follow-up, with significantly greater T2-FLAIR reduction with GTR versus subtotal resection (p<0.05). There was a trend towards decreased steroid use, from 8mg daily dexamethasone-equivalent (range 2–36) preoperatively to 3mg 12-months postoperatively (range 1–8; p=0.063).

Conclusions

RN resection conferred both durable T2-FLAIR reduction, which correlated with EOR, and reduced steroid dependency.
Motherhood‐induced gene expression in the mouse medial amygdala: Changes induced by pregnancy and lactation but not by pup stimuli
Authors: Abellán‐Álvaro María , Ayala Guillermo , Barneo‐Muñoz Manuela , Martínez‐García Fernando , Agustín‐Pavón Carmen , Lanuza Enrique
Published: August 2021

During lactation, adult female mice display aggressive responses toward male intruders, triggered by male‐derived chemosensory signals. This aggressive behavior is not shown by pup‐sensitized virgin females sharing pup care with dams. The genetic mechanisms underlying the switch from attraction to aggression are unknown. In this work, we investigate the differential gene expression in lactating females expressing maternal aggression compared to pup‐sensitized virgin females in the medial amygdala (Me), a key neural structure integrating chemosensory and hormonal information. The results showed 197 genes upregulated in dams, including genes encoding hormones such as prolactin, growth hormone, or follicle‐stimulating hormone, neuropeptides such as galanin, oxytocin, and pro‐opiomelanocortin, and genes related to catecholaminergic and cholinergic neurotransmission. In contrast, 99 genes were downregulated in dams, among which we find those encoding for inhibins and transcription factors of the Fos and early growth response families. The gene set analysis revealed numerous Gene Ontology functional groups with higher expression in dams than in pup‐sensitized virgin females, including those related with the regulation of the Jak/Stat cascade. Of note, a number of olfactory and vomeronasal receptor genes was expressed in the Me, although without differences between dams and virgins. For prolactin and growth hormone, a qPCR experiment comparing dams, pup‐sensitized, and pup‐naïve virgin females showed that dams expressed higher levels of both hormones than pup‐naïve virgins, with pup‐sensitized virgins showing intermediate levels. Altogether, the results show important gene expression changes in the Me, which may underlie some of the behavioral responses characterizing maternal behavior.