bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Tianlai dish pathfinder array: design, operation, and performance of a prototype transit radio interferometer
Authors: Wu Fengquan , Li Jixia , Zuo Shifan , Chen Xuelei , Das Santanu , Marriner John P , Oxholm Trevor M , Phan Anh , Stebbins Albert , Timbie Peter T , Ansari Reza , Campagne Jean-Eric , Chen Zhiping , Cong Yanping , Huang Qizhi , Kwak Juhun , Li Yichao , Liu Tao , Liu Yingfeng , Niu Chenhui , Osinga Calvin , Perdereau Olivier , Peterson Jeffrey B , Podczerwinski John , Shi Huli , Siebert Gage , Sun Shijie , Tian Haijun , Tucker Gregory S , Wang Qunxiong , Wang Rongli , Wang Yougang , Wu Yanlin , Xu Yidong , Yu Kaifeng , Yu Zijie , Zhang Jiao , Zhang Juyong , Zhu Jialu 
Published: July 2021

ABSTRACT
The Tianlai Dish Pathfinder Array is a radio interferometer designed to test techniques for 21 cm intensity mapping in the post-reionization universe as a means for measuring large-scale cosmic structure. It performs drift scans of the sky at constant declination. We describe the design, calibration, noise level, and stability of this instrument based on the analysis of about 5% of 6200 h of on-sky observations through 2019 October. Beam pattern determinations using drones and the transit of bright sources are in good agreement, and compatible with electromagnetic simulations. Combining all the baselines, we make maps around bright sources and show that the array behaves as expected. A few hundred hours of observations at different declinations have been used to study the array geometry and pointing imperfections, as well as the instrument noise behaviour. We show that the system temperature is below 80 K for most feed antennas and that noise fluctuations decrease as expected with integration time, at least up to a few hundred seconds. Analysis of long integrations, from 10 nights of observations of the North Celestial Pole (NCP), yielded visibilities with amplitudes of 20–30 mK, consistent with the expected signal from the NCP radio sky with ${\lt}10\,$ mK precision for 1 MHz × 1 min binning. Hi-pass filtering the spectra to remove smooth spectrum signal yields a residual consistent with zero signal at the $0.5\,$ mK level.
Statistical recovery of the BAO scale from multipoles of the beam-convolved 21 cm correlation function
Authors: Kennedy Fraser , Bull Philip 
Published: July 2021

ABSTRACT
Despite being designed as an interferometer, the MeerKAT radio array (a Square Kilometre Array pathfinder) can also be used in autocorrelation (‘single-dish’) mode, where each dish scans the sky independently. Operating in this mode allows extremely high survey speeds to be achieved, albeit at significantly lower angular resolution. We investigate the recovery of the baryon acoustic oscillation (BAO) scale from multipoles of the redshift-space correlation function as measured by a low angular resolution 21 cm intensity mapping survey of this kind. Our approach is to construct an analytic model of the multipoles of the correlation function and their covariance matrix that includes foreground contamination and beam resolution effects, which we then use to generate an ensemble of mock data vectors from which we attempt to recover the BAO scale. In line with previous studies, we find that recovery of the transverse BAO scale α⊥ is hampered by the strong smoothing effect of the instrumental beam with increasing redshift, while the radial scale α∥ is much more robust. The multipole formalism naturally incorporates transverse information when it is available however, and so there is no need to perform a radial-only analysis. In particular, the quadrupole of the correlation function preserves a distinctive BAO ‘bump’ feature even for large smoothing scales. We also investigate the robustness of BAO scale recovery to beam model accuracy, severity of the foreground removal cuts, and accuracy of the covariance matrix model, finding in all cases that the radial BAO scale can be recovered in an accurate, unbiased manner.
Carbon-enhanced stars with short orbital and spin periods
Authors: Whitehouse L J , Farihi J , Howarth I D , Mancino S , Walters N , Swan A , Wilson T G , Guo J 
Published: July 2021

ABSTRACTMany characteristics of dwarf carbon stars are broadly consistent with a binary origin, including mass transfer from an evolved companion. While the population overall appears to have old-disc or halo kinematics, roughly 2 per cent of these stars exhibit  Hα emission, which in low-mass main-sequence stars is generally associated with rotation and relative youth. Its presence in an older population therefore suggests either irradiation or spin-up. This study presents time-series analyses of photometric and radial-velocity data for seven dwarf carbon stars with  Hα emission. All are shown to have photometric periods in the range 0.2–5.2 d, and orbital periods of similar length, consistent with tidal synchronization. It is hypothesized that dwarf carbon stars with emission lines are the result of close-binary evolution, indicating that low-mass, metal-weak, or metal-poor stars can accrete substantial material prior to entering a common-envelope phase.
Spiral instabilities: little interaction with a live halo
Authors: Sellwood J A 
Published: July 2021

ABSTRACT
In order to address the question of whether spiral disturbances in galaxy discs are gravitationally coupled to the halo, we conduct simulations of idealized models of disc galaxies. We compare growth rates of spiral instabilities in identical mass models in which the halo is held rigid or is represented by particles drawn from an equilibrium distribution function. We examine cases of radial and azimuthal bias in the halo velocity ellipsoid in one of our models, and an isotropic velocity distribution in both. We find at most marginal evidence for an enhanced growth rate of spiral modes caused by a halo supporting response. We also find evidence for very mild dynamical friction between the spiral disturbance and the halo. We offer an explanation to account for the different behaviour between spiral modes and bar modes, since earlier work had found that bar instabilities became significantly more vigorous when a responsive halo was substituted for an equivalent rigid mass distribution. The barely significant differences found here justify the usual simplifying approximation of a rigid halo made in studies of spiral instabilities in galaxies.
RENET2: high-performance full-text gene–disease relation extraction with iterative training data expansion
Authors: Su Junhao , Wu Ye , Ting Hing-Fung , Lam Tak-Wah , Luo Ruibang 
Published: July 2021

Abstract
Relation extraction (RE) is a fundamental task for extracting gene–disease associations from biomedical text. Many state-of-the-art tools have limited capacity, as they can extract gene–disease associations only from single sentences or abstract texts. A few studies have explored extracting gene–disease associations from full-text articles, but there exists a large room for improvements. In this work, we propose RENET2, a deep learning-based RE method, which implements Section Filtering and ambiguous relations modeling to extract gene–disease associations from full-text articles. We designed a novel iterative training data expansion strategy to build an annotated full-text dataset to resolve the scarcity of labels on full-text articles. In our experiments, RENET2 achieved an F1-score of 72.13% for extracting gene–disease associations from an annotated full-text dataset, which was 27.22, 30.30, 29.24 and 23.87% higher than BeFree, DTMiner, BioBERT and RENET, respectively. We applied RENET2 to (i) ∼1.89M full-text articles from PubMed Central and found ∼3.72M gene–disease associations; and (ii) the LitCovid articles and ranked the top 15 proteins associated with COVID-19, supported by recent articles. RENET2 is an efficient and accurate method for full-text gene–disease association extraction. The source-code, manually curated abstract/full-text training data, and results of RENET2 are available at GitHub.
ECOA-5. Integrative 3D spatial characterization of genomic and epigenomic intratumoral heterogeneity in glioblastoma
Authors: Mathur Radhika , Wang Qixuan , Schupp Patrick , Hilz Stephanie , Hong Chibo , Smirnov Ivan , Lafontaine Marisa , Nair Devika , Iyyanaki Sriranga , Phillips Joanna , Chang Susan , Li Yan , Lupo Janine , Oldham Michael , Yue Feng , Costello Joseph 
Published: July 2021

Abstract
Treatment failure in glioblastoma is often attributed to intratumoral heterogeneity (ITH), which fosters tumor evolution and selection of therapy-resistant clones. While genomic alterations are known contributors to ITH, emerging studies highlight functional roles for epigenomic ITH which integrates differentiation status, stochastic events, and microenvironmental inputs. Here, we have established a novel platform for integrative characterization of genomic and epigenomic ITH of glioblastoma in three-dimensional (3-D) space. In collaboration with neurosurgeons and biomedical imaging experts, we utilize 3-D surgical neuro-navigation to safely acquire ~10 tumor samples per patient representing maximal anatomical diversity. We conduct whole-exome sequencing, RNA sequencing, and assay for transposase-accessible chromatin using sequencing (ATAC-Seq) on each sample. The spatial location of each sample is mapped by its 3-D coordinates, allowing 360-degree visualization of genomic and epigenomic ITH for each patient. We demonstrate this approach on 8 patients with primary IDH-WT glioblastoma (83 spatially mapped samples), providing unprecedented insight into their spatial organization at the genomic and epigenomic levels. We link genetically defined tumor subclones to patterns of open chromatin and gene regulation, revealing underlying transcription factor binding at active promoters and enhancers. We also identify ITH in whole-genome doubling and focal oncogene amplification events in multiple patients, which we then link with epigenomic ITH. Further, to study microenvironmental inputs and their contribution to epigenomic ITH, we conduct deconvolution of RNA sequencing and ATAC-Seq data by analyzing feature co-variation. We resolve the 3-D spatial organization of immune, neural, and other nontumor cell types present in glioblastoma, characterizing their functional states and interactions with tumor cells. This work provides the most comprehensive spatial characterization of genomic and epigenomic ITH to date in glioblastoma. As a resource for further investigation, we have developed an interactive data sharing platform – The 3D Glioma Atlas – that enables 360-degree visualization of both genomic and epigenomic ITH.
ECOA-10. Integrated genomic and clinical analysis of BRAF-mutated glioma in adults
Authors: Langat Pinky , Li Taibo , Bi Wenya Linda , Schreck Karisa C 
Published: July 2021

Abstract
BRAF alterations are recognized as a significant driver of disease in pediatric low-grade glioma (pLGG) but the implications of BRAF alterations on the natural history and response to treatment are unclear in adult glioma. We characterized the molecular and clinical features of a multi-institutional cohort of adults with BRAF-mutated gliomas. We identified patients with glioma containing BRAF alterations on sequencing in multi-institutional cohorts (Dana-Farber/Brigham Cancer Center, Johns Hopkins Hospital, GENIE, TCGA). BRAF alterations were grouped into previously defined classes: I (V600E; RAS-independent/dimerization-independent), II (RAS-independent/dimerization-dependent), III (RAS-dependent/dimerization-dependent) in addition to BRAF copy number gains, fusions, and other. We interrogated 289 BRAF-altered gliomas (199 patients &gt;=18yrs, 90 patients &lt;18yrs; range 0-85yrs), and observed histopathologic and molecular differences between BRAF-altered gliomas in adults versus pediatric patients. Amongst adults, the most common BRAF alterations were Class I followed by copy number gains, with glioblastoma (GBM) the most prevalent histology. In comparison, pediatric gliomas in our cohort frequently harbored Class I mutations followed by BRAF fusions, with primarily pilocytic astrocytoma and pLGG histologies. Principal component analysis and correlation analysis revealed molecular features associated with gliomas of different BRAF alterations and histologies, including mutation of NF1, a negative regulator of RAS, which was significantly associated with class II/III BRAF alterations (64.3%) and not observed in BRAFV600E-mutated gliomas (0%, n=62) (p&lt;0.0001). Demographic and molecular features were evaluated for correlates for adult glioma risk stratification. Comparative survival analysis showed no significant difference between adult GBM harboring Class I compared to other BRAF alterations, whereas young adult age (18-35yrs) was associated with improved outcomes (p&lt;0.05). Among 86 GBM patients with detailed clinicopathologic data, 7 received RAF-targeted therapy, with variable clinical response. This cohort of BRAF-altered adult gliomas demonstrates a broad range of molecular alterations with implications for treatment sensitivity and patient risk stratification.
MOMC-5. Systems pharmacogenomics identifies novel targets and clinically actionable therapeutics for medulloblastoma
Authors: Genovesi Laura , Millar Amanda , Tolson Elissa , Singleton Matthew , Hassall Emily , Kojic Marija , Brighi Caterina , Girald Emily , Andradas Clara , Kuchibhotla Mani , Endersby Raelene , Gottardo Nicholas , Bernard Anne , Adolphe Christelle , Olson James , Davis Melissa , Wainwright Brandon 
Published: July 2021

Abstract

Background
Medulloblastoma (MB) is the most common malignant paediatric brain tumour and a leading cause of cancer-related mortality and morbidity. Existing treatment protocols are aggressive in nature resulting in significant neurological, intellectual and physical disabilities for the children undergoing treatment. Clearly, there is an urgent need for improved, targeted therapies that minimize these harmful side effects.

Methods
We identified candidate drugs for MB using a network-based systems-pharmacogenomics approach: based on results from a functional genomics screen, we identified a network of interactions implicated in human MB growth regulation. We then integrated drugs and their known mechanisms of action, along with gene expression data from a large collection of medulloblastoma patients to identify drugs with potential to treat MB.

Results
Our analyses identified drugs targeting CDK4, CDK6, and AURKA as strong candidates for MB; all of these genes are well validated as drug targets in other tumour types. We also identified non-WNT MB as a novel indication for drugs targeting TUBB, CAD, SNRPA, SLC1A5, PTPRS, P4HB and CHEK2. Based upon these analyses we subsequently demonstrated that one of these drugs, the new microtubule stabilizing agent, ixabepilone, blocked tumour growth in vivo in mice bearing Sonic Hedgehog and Group 3 patient-derived xenograft tumours, providing the first demonstration of its efficacy in MB.

Conclusions
Our findings confirm that this data-driven systems pharmacogenomics strategy is a powerful approach for the discovery and validation of novel therapeutic candidates relevant to MB treatment, and along with data validating ixabepilone in PDX models of the two most aggressive subtypes of medulloblastoma, we present the network analysis framework as a resource for the field.
NGMA-4. Creation of a MADR brain tumor single-cell atlas for examination of inter-/intratumor heterogeneity and the results of genetic perturbations in a diverse array of brain tumor subtypes
Authors: Pacheco David Rincon Fernandez , Park Hannah , Grausam Katie , Breunig Joshua 
Published: July 2021

Abstract
We have recently established mosaic analysis by dual recombinase-mediated cassette exchange (MADR), which permits stable labeling of mutant cells expressing transgenic elements from precisely defined chromosomal loci. MADR provides a toolkit of elements for combinatorial labeling, inducible/reversible transgene manipulation, VCre recombinase expression, and genetic manipulation of human cells. Further, we have demonstrated the versatility of MADR by creating glioma models with mixed, reporter-identified zygosity or with “personalized” driver mutations from pediatric glioma. For example, introducing H3f3a (aka H3.3) mutation variants with MADR regulates the spatiotemporal profile of glioma, and single-cell RNA and ATAC sequencing analysis demonstrates a recapitulation of developmental hierarchy seen in K27M mutant human glioma. Moreover, we have generated novel models of H3.3 WT glioma, H3.3 G34R glioma, and supratentorial ependymoma using patient-derived oncofusion transgenes. These models display a high degree of phenotypic fidelity and we now compare these models on a single-cell level with our previous models, mouse single-cell RNA glioma datasets from other studies, and human tumor cell transcriptomes. Our multi-omics approach includes integration of ChIP-seq/Cut&Tag datasets, single-cell ATAC, and single-cell Cut&Tag datasets.
Moreover, we have engineered a novel methodology for inducible gain- and loss-of function perturbation studies in vivo. Using ETS transcription factors as a proof-of-principle, we overlay these genetic perturbations on the glioma atlas to examine the gene networks altered by precise molecular manipulations.
We hope that these combined approaches will enable researchers to discover disease mechanisms with increased resolution and test therapeutics in credentialed pre-clinical disease models.
OPTC-3. Differential Synapse-Related Gene Expression Identifies Glioma Subtypes and Predicts Prognosis
Authors: Surapaneni Akhil , Kohli Vik , Ahmed Yousuf , Seghers Matthew , Kuo John 
Published: July 2021

Abstract
Synaptic connectivity between gliomas and adjacent brain was recently implicated in tumorigenesis. However, the interaction of synapse-related genes (SRGs) with patient survival and with established clinical and molecular glioma subtypes merit further study in a large patient cohort. We characterized differential expression of SRGs in gliomas and investigated SRG expression as putative clinical biomarkers in a large glioma cohort.
Expression of 1189 SRGs was interrogated via RNA sequencing analysis in 603 gliomas (LGG n=451, GBM n=152) of The Cancer Genome Atlas. SRG expression patterns partitioned gliomas into two clusters that were more distinctive than priorly identified glioma subtypes. The two glioma clusters showed significantly low (14.9 months) or high median survival (105.1 months; Hazard Ratio = 7.1, 95% CI: [5.32, 9.78], p = 1.29e-46 using a log-rank test). The high survival cluster showed overrepresentation of known pro-neural and neural subtypes and IDH-mutated gliomas (p&lt;0.00001). The mesenchymal and classic GBMs and IDH-wild type gliomas were overrepresented in the low survival cluster (p &lt; 0.00001). In addition, an Elastic Net Cox Regression model identified 34 SRGs whose expression significantly predicted differential survival and a prognostic Synapse Gene Score (SGS) was created. Using an accelerated failure time model, SGS predicted survival in the overall gliomas after adjusting for IDH-1 mutation (HR = 2.51, 95% CI: [2.27, 2.7496], p&lt;0.00001), and in the IDH-1 mutant cohort after adjusting for 1p/19q co-deletion (HR = 2.05, 95% CI: [1.73, 2.37], p&lt;0.00001).
Our analysis shows that gliomas can be distinctively clustered by differential SRGs expression, suggesting that synapse-related proteins may contribute to tumorigenesis via multiple mechanisms. Furthermore, the potential utility of SRGs as clinical glioma biomarkers is supported by our creation of a prognostic SGS. Future studies elucidating interactions between tumorigenesis and synaptic mechanisms may reveal additional insights for glioma biology and therapeutic targeting.
OMRT-11. The effect of microenvironment on glioblastoma stem cells therapeutic resistance
Authors: Turnsek Tamara Lah , Breznik Barbara , Majc Bernarda , Novak Metka , Porčnik Andrej , Habič Anamarija , Mlinar Mateja , Bošnjak Roman 
Published: July 2021

Abstract
Epithelial-to-mesenchymal transition (EMT) is an essential molecular and cellular process in physiologic processes and invasion of various types of carcinoma and glioblastoma (GBM) cells. EMT is activated and regulated by specific endogenous triggers in complex network of intercellular interactions and signaling pathways. The hallmark of cancer-linked EMT are intermediate states that show notable cell plasticity, characteristic of cancer stem cells (CSCs), including glioblastoma stem cells – GSCs. GSCs resistance to irradiation (IR) and temozolomide (TMZ) chemotherapy is responsible for early relapses, even at distant brain sites. As GSCs are mostly homing to their “niches” as slowly-dividing GSC-subtype, mimicking a proneural-like non- invasive phenotype PN-genotype, we assume that this, by undergoing an EMT-like transition, GSCs are-reprogrammed to an invasive mesenchymal (MES) GBs/GSCs phenotype in a processes, called PMT (1). However, it is not known, if and by which environmental cues within the niche, this transition of GSCs is induced in vivo. In this work, we are presenting the transriptome data obtained when we exposed GSC spheroids to irradiation alone, TMZ alone and to the combined treatment in vitro and compared their differential genetic fingerprints related to EMT/PMT transition to the GSCs PMT transition, when embedded in their natural microenvironment in the GBM organoid model. The differential gene expression upon GSCs therapeutic perturbation (when alone and vs in the tumoroid microenvironment) will reveal the effects of the major candidate genes, associated with micronevironmendt stromal cells and matrix are contributing their observed EMT/PMT transition of GSCs in vivo.
•1. Majc, B., Sever, T., Zarić, M, Breznik, B., Turk, B, Lah Turnšek, T. Epithelial- to-mesenchymal transition as the driver of changing carcinoma and glioblastoma microenvironment. DOI: 10.1016/j.bbamcr.2020.118782