bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractEcoimmunology 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

SUMMARYSources 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

Abstract
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

ABSTRACT
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

ABSTRACTThere 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

ABSTRACT
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

Abstract
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&gt;2, adj.p-value&lt;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

Abstract
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

Abstract

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

Abstract

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

Abstract
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

Abstract

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

Abstract

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 &lt;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 &gt;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 &lt;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.