bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using Deep Learning for Big Spatial Data Partitioning
Authors: Vu Tin , Belussi Alberto , Migliorini Sara , Eldway Ahmed 
Published: August 2020

This article explores the use of deep learning to choose an appropriate spatial partitioning technique for big data. The exponential increase in the volumes of spatial datasets resulted in the development of big spatial data frameworks. These systems need to partition the data across machines to be able to scale out the computation. Unfortunately, there is no current method to automatically choose an appropriate partitioning technique based on the input data distribution.
This article addresses this problem by using deep learning to train a model that captures the relationship between the data distribution and the quality of the partitioning techniques. We propose a solution that runs in two phases, training and application. The offline training phase generates synthetic data based on diverse distributions, partitions them using six different partitioning techniques, and measures their quality using four quality metrics. At the same time, it summarizes the datasets using a histogram and well-designed skewness measures. The data summaries and the quality metrics are then use to train a deep learning model. The second phase uses this model to predict the best partitioning technique given a new dataset that needs to be partitioned. We run an extensive experimental evaluation on big spatial data, and we experimentally show the applicability of the proposed technique. We show that the proposed model outperforms the baseline method in terms of accuracy for choosing the best partitioning technique by only analyzing the summary of the datasets.
Expression of the Androgen Receptor Governs Radiation Resistance in a Subset of Glioblastomas Vulnerable to Antiandrogen Therapy
Authors: Werner Christian K. , Nna Uchechi J. , Sun Hanshi , Wilder-Romans Kari , Dresser Joseph , Kothari Ayesha U. , Zhou Weihua , Yao Yangyang , Rao Arvind , Stallard Stefanie , Koschmann Carl , Bor Tarik , Debinski Waldemar , Hegedus Alexander M. , Morgan Meredith A. , Venneti Sriram , Baskin-Bey Edwina , Spratt Daniel E. , Colman Howard , Sarkaria Jann N. , Chinnaiyan Arul M. , Eisner Joel R. , Speers Corey , Lawrence Theodore S. , Strowd Roy E. , Wahl Daniel R. 
Published: August 2020

Abstract
New approaches are needed to overcome intrinsic therapy resistance in glioblastoma (GBM). Because GBMs exhibit sexual dimorphism and are reported to express steroid hormone receptors, we reasoned that signaling through the androgen receptor (AR) could mediate therapy resistance in GBM, much as it does in AR-positive prostate and breast cancers. We found that nearly half of GBM cell lines, patient-derived xenografts (PDX), and human tumors expressed AR at the transcript and protein level—with expression levels overlapping those of primary prostate cancer. Analysis of gene expression datasets also revealed that AR expression is higher in GBM patient samples than normal brain tissue. Multiple clinical-grade antiandrogens slowed the growth of and radiosensitized AR-positive GBM cell lines and PDXs in vitro and in vivo. Antiandrogens blocked the ability of AR-positive GBM PDXs to engage adaptive transcriptional programs following radiation and slowed the repair of radiation-induced DNA damage. These results suggest that combining blood–brain barrier permeable antiandrogens with radiation may have promise for patients with AR-positive GBMs.
Abstract A15: Improving immune recognition of shared tumor-associated antigens in pediatric tumors using a multimodal oncolytic virus
Authors: Ghonime Mohammed G. , Roth Justin C. , Barker Naomi J. , Miller Katherine E. , Mardis Elaine R. , Walker Christopher M. , Cassady Kevin A. 
Published: August 2020

Abstract
Immunotherapy is an attractive treatment approach for children because of its precision and reduced toxicity. Unfortunately, pediatric solid tumors often evade immune recognition. Like adult cancers, the immunosuppressive tumor microenvironment can restrict immune activity. Further complicating this, pediatric cancers have low mutation rates, creating fewer antigenic targets for the immune response. We therefore developed a multimodal oncolytic virus that harnesses the antiviral immune response and redirects it against shared tumor-associated antigen (TAA) in the tumor. Engineering a TAA, Ephrin A2 (EphA2), into the oncoviral (OV) genome circumvents transcriptional/translational arrest and allows TAA overexpression during infection. Our results show that virus-based EphA2 expression (C57BL/6 sequence) induces an immune-mediated antitumor response in syngeneic C57BL/6-based brain and peripheral tumor models, improving survival (e.g., CT2A brain tumor median survival: 43d-TAA virus vs. 30d-parent virus, 29d-Saline; overall survival: 44.4%-TAA virus vs. 12%-parent virus vs 0%-Saline, *p=0.0233). TAA-virus treatment increases CD8 memory effector-like cells in tumor infiltrates (CD62L+, CD44+) and rechallenge studies show abscopal effect in TAA-virus treated survivors. Peptide pulsing studies using splenocytes from survivors show that viral TAA expression induces a circulating EphA2-specific CD8 effector-like (CD8+, CD25+, Granzyme B+) population (14.1%-TAA virus vs 2.6%-parent virus, 0.6% Saline, **p≤0.0098). This multimodal viral platform harnesses the oncolytic and immunostimulatory properties of a next-generation OV to enhance immune activity against tumors expressing shared tumor antigens. Our results suggest that this flexible viral-based platform provides an effective in situ antitumor vaccination approach and could be engineered against multiple antigens for low mutational load tumors.
Citation Format: Mohammed G. Ghonime, Justin C. Roth, Naomi J. Barker, Katherine E. Miller, Elaine R. Mardis, Christopher M. Walker, Kevin A. Cassady. Improving immune recognition of shared tumor-associated antigens in pediatric tumors using a multimodal oncolytic virus [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr A15.
Abstract A20: Single-cell immune TCR repertoire profiling in the context of immunotherapy by using three 10x Genomics libraries
Authors: Qi Yuan , Im Jin Seon , Su Xiaoping 
Published: August 2020

Abstract
10x Genomics single-cell sequencing provides a comprehensive and scalable solution for cell characterization and gene expression profiling of hundreds to tens of thousands of cells. For performance comparison of single-cell immune TCR repertoire profiling, we tested three libraries: (1) 5-prime gene expression, (2) direct enrichment for TCR, and (3) post-cDNA-amplification enrichment for TCR, on two invariant natural killer T (iNKT) cells, on B240 and B241, with iNKT purity at 90% and 45%, respectively. We also performed correlation analysis between gene expression data and clonotype data by library 3. About 1,100 cells of B240 and 580 cells of B241 were sequenced. The numbers of productive clonotypes of B240 were identified as 165, 284, and 332 for the three libraries, respectively, while 47 clonotypes overlapped among the libraries. The numbers of productive clonotypes of B241 were 88, 152, and 148, respectively, while 35 clonotypes overlapped. Each sample is a mixture of iNK T cells and non-invariant NK T cells. We were able to identify the clusters of iNKT cells using the 5’ gene expression data by library 1 in tSNE plots for both B240 and B241. More importantly, the clusters correlated strongly with the TCR clonotypes identifying iNKT cells by library 3. Based upon our data, we noticed that the number of clonotypes identified is proportional to the number of cells sequenced regardless of libraries. Library 1 has low sensitivity in terms of clonotype detection, due to un-enrichment of TCR genes, and mainly detected single chain in each cell (beta chain most of the time). The other two libraries are able to identify high and similar number of clonotypes. However, library 3 is able to associate gene expression pattern with TCR clonotype usage, which is a big advantage over the other two libraries for 10x Genomics single-cell immune TCR repertoire profiling.
Note: This abstract was not presented at the conference.
Citation Format: Yuan Qi, Jin Seon Im, Xiaoping Su. Single-cell immune TCR repertoire profiling in the context of immunotherapy by using three 10x Genomics libraries [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr A20.
Abstract A22: YAP1 knockout in vitro models of medulloblastoma showed improved response to sonidegib
Authors: Cruzeiro Gustavo Alencastro Veiga , de Almeida Magalhães Taciani , de Sousa Ribeiro Graziella , Ferreira das Chagas Pablo , Silva Ricardo Bonfim , Chatterje Sampurna , Scrideli Carlos Alberto , Tone Luiz Gonzaga 
Published: August 2020

Abstract
Background: Medulloblastoma (MB) is the most common malignant brain tumor in childhood. Despite improvement in current treatment, children still suffer from long-term sequelae resulting from standard care therapy. World Health Organization considers MB as 4 distinct entities: SHH, WNT, Group 3, and Group 4. The most aggressive variant of SHH MB is the bearer of TP53 mutation and it is resistant to standard chemo/radiation therapy. Therefore, novel treatments modalities are urgently needed. In this study we aimed to evaluate the biologic relevance of YAP1 in SHH MB human cell lines bearers of TP53 mutation and its potential as a new therapeutic target.
Methods: We generated YAP1 CRISPR/CAS9 knockout single-cell clones of human cell lines DAOY and UW228 assigned as “MB SHH-like” and bearers of TP53 mutation. We picked sonidegib as a standard-care chemotherapy for in vitro SHH MB model and assessed the apoptosis/necrosis using Annexin V/Propidium-Iodide staining to identify positive cells through flow cytometry. Proliferation and colony formation were assessed by cell counting Kit 8 proliferation assay and GIEMSA staining, respectively. Additionally, we used verteporfin, a YAP1 inhibitor, and evaluated its effect on cell proliferation.
Findings: Using single-cell cloning, we successfully generated DAOY and UW228 cell lines with depleted YAP1 protein. YAP1 knockout cell lines DAOY and UW228 showed improved response to sonidegib regarding i) decrease in proliferation (p&lt;0.05), ii) apoptosis induction (p&lt;0.01), and iii) colony formation abrogation (p&lt;0.001). In order to step towards translation, we tested verteporfin (YAP1 inhibitor) and found that this compound successfully reduced proliferation in both cell lines (p&lt;0.05).
Conclusion: Although YAP1 depletion showed association with better response to sonidegib, a smoothened inhibitor, more experiments are needed to evaluate if the in vitro findings might shed new light on a potential synergistic combination between sonidegib and verteporfin and provide a good rationale for targeted therapy.
Citation Format: Gustavo Alencastro Veiga Cruzeiro, Taciani de Almeida Magalhães, Graziella de Sousa Ribeiro, Pablo Ferreira das Chagas, Ricardo Bonfim Silva, Sampurna Chatterje, Carlos Alberto Scrideli, Luiz Gonzaga Tone. YAP1 knockout in vitro models of medulloblastoma showed improved response to sonidegib [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr A22.
Abstract A33: HIF2 in pediatric high-grade glioma and its targeting
Authors: Fuchs Quentin , Blandin Anne Florence , Rebel Isabelle Lelong , Pierrevelcin Marina , Dontenwill Monique , Entz-Werlé Natacha 
Published: August 2020

Abstract
Pediatric high-grade gliomas (pHGGs) represent a very dismal disease that is needing new innovative compound for treatment. Despite the past discovery of histone H3 driver mutations, we are not able for instance to stop this induced process on epigenetic remodulation. Therefore, there is since a decade proactive works aimed to discover new targetable proteins in these tumors. In our recent previous works in pHGGs, we highlighted HIF2alpha as a biomarker of worse prognosis and outcome and a key in treatment resistance. Therefore, this new project was designed to determine in several patient-derived cell lines (5 PDCLs) the presence of HIF2alpha, its role and its induction in normoxic and hypoxic microenvironment concomitantly by immunofluorescence and Western blot assessments and RNA sequencing analyses. Complementary ChipSeq was also performed using HIF2 antibodies to determine its role as a transmission factor. Specific promoters were involved. After the confirmation of its frequent presence in multiple PDCLs initiated from thalamic pHGGs and DIPG, we used allosteric inhibitors to target HIF2alpha. Surprisingly, this protein was expressed constantly in hypoxic and normoxic conditions and specifically in PDCLs bearing stem cell features. Specific expression associations were established between stemness markers and HIF2alpha. To go further, we tested specific HIF2A inhibitors, which were having an impact on cell proliferation and on the decrease of the target itself. In conclusion, HIF2 seem to be a major biomarker in pHGGs that might be targeted, and it is a useful new opportunity for pHGGs treatments.
Citation Format: Quentin Fuchs, Anne Florence Blandin, Isabelle Lelong Rebel, Marina Pierrevelcin, Monique Dontenwill, Natacha Entz-Werlé. HIF2 in pediatric high-grade glioma and its targeting [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr A33.
Abstract A38: Validation of potential therapies for treatment of fatal pediatric brain tumors DIPG and AT/RT using a novel rapid intracranial model in zebrafish
Authors: Kaur Harpreet , Guo Huizi , White David , Green Peter , Hector Alara M. , Akhtarkhavari Sepehr , Bhargava Anukriti , Shah Smit , Eberhart Charles G. , Mumm Jeffrey , Raabe Eric H. 
Published: August 2020

Abstract
Diffuse intrinsic pontine glioma (DIPG) and atypical teratoid/rhabdoid tumors (AT/RT) are deadly pediatric brain tumors. Developing new targets and therapeutics are urgently needed. We have previously shown that multiple primary brain tumors and cell lines express increased amounts of the epigenetic modifier and DNA binding oncoprotein high-mobility group AT-hook 2 (HMGA2). Targeting HMGA2 using short hairpins decreased AT/RT and glioma growth in xenografted mice. We hypothesized that pharmacologic inhibition of HMGA proteins using DNA minor-groove binding drugs such as quinacrine would decrease tumor growth due to displacement of HMGA proteins from DNA. Quinacrine is a safe and widely used treatment for pediatric malaria and parasitic infections. We used quinacrine in six patient-derived cell lines: three AT/RT (BT37, CHLA-05, CHLA-266) and three DIPG (JHHDIPG1, SUDIPGXIII, SF7761). Using quinacrine fluorescence as a surrogate, we can achieve micromolar concentration of quinacrine in the mouse and zebrafish brain after oral administration without overt toxicity. In both tumor cell lines, quinacrine causes a dose-dependent reduction in proliferation (BrdU) and increase in apoptosis (cleaved caspase-3 and cleaved PARP) compared to vehicle-treated cells (P&lt;0.01). Quinacrine had no effect on growth of normal hindbrain neural stem and progenitor cells. Treatment of mice bearing ATRT flank tumors with quinacrine resulted in decreased tumor volume compared to vehicle-treated mice (P&lt;0.05). Current mouse intracranial DIPG models can take 6-9 months due to long latency. To validate quinacrine orthotopically in DIPG, we developed a novel model in zebrafish wherein we injected fluorescent DIPG cells into the developing zebrafish blastula. Five days post injection, DIPG cells had homed to the zebrafish brain. Treatment of xenografted zebrafish with quinacrine for 48 hours decreased DIPG growth by 40% as measured by fluorescence, suggesting that minor groove binding drugs such as quinacrine are a viable treatment strategy for these tumors. Future studies are aimed at investigating the mechanism of quinacrine in these tumors.
Citation Format: Harpreet Kaur, Huizi Guo, David White, Peter Green, Alara M. Hector, Sepehr Akhtarkhavari, Anukriti Bhargava, Smit Shah, Charles G. Eberhart, Jeffrey Mumm, Eric H. Raabe. Validation of potential therapies for treatment of fatal pediatric brain tumors DIPG and AT/RT using a novel rapid intracranial model in zebrafish [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr A38.
Abstract A43: Effects of transcriptional dysregulation on the DNA damage response in Ewing’s sarcoma
Authors: Rollins Matthew G. , Schwartz Jacob C. 
Published: August 2020

Abstract
Ewing’s sarcoma is a soft-tissue bone malignancy characterized by a translocation event wherein the N-terminal low complexity domain of EWSR1 is fused with the DNA binding domain of the ETS transcription factor Fli1. The resulting EWS-Fli1 fusion protein drives expression of oncogenes and knockdown of tumor-suppressor proteins. More specifically, EWS-Fli1 acts as transcriptional regulator by helping recruit RNA Pol II to promoter regions, which is subsequently phosphorylated by CDK9 to escape initiation into elongation. Interestingly, Ewing’s sarcoma is particularly susceptible to chemotherapy compared to other cancers; however, the underlying reason for this sensitivity to DNA damage has not been elucidated. Given EWS-Fli1’s role in disrupting transcription, it was hypothesized that EWS-Fli1 is concurrently disrupting the DNA damage response. Here, a combination of CDK9 inhibition with DNA damage was found to drastically diminish cell viability in Ewing’s cell lines but not in non-Ewing’s osteosarcoma or HEK293 cells. Ordinarily, after DNA damage γH2A.X phosphorylation occurs on histones near sites of damaged DNA early during the DNA damage response to signal DNA damage repair initiation. Further work has shown Ewing’s cells undergoing the combination treatment above have a marked decrease in the DNA damage marker γH2A.X as compared to non-Ewing’s cells. Together, these results suggest Ewing’s sarcoma cells are sensitized to DNA damage due in part to transcriptional dysregulation.
Citation Format: Matthew G. Rollins, Jacob C. Schwartz. Effects of transcriptional dysregulation on the DNA damage response in Ewing’s sarcoma [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr A43.
Abstract A57: Feasibility of physical activity in children with cancer: A multidisciplinary program in the context of the VIE study
Authors: Caru Maxime , Duhamel Gabrielle , Marcil Valérie , Sultan Serge , Meloche Caroline , Bouchard Isabelle , Drouin Simon , Bertout Laurence , Laverdière Caroline , Sinnett Daniel , Curnier Daniel 
Published: August 2020

Abstract
Purpose: Cancer is one of the leading causes of death in the world. The physiologic and psychological benefits of physical activity have been shown in children with cancer. However, almost one in two cancer patients do not follow the physical activity guidelines. The aim of this study will be to assess the feasibility of a physical activity program intervention in pediatric oncology and to assess the barriers and facilitators in the success or failure of this physical activity program.
Methods: The VIE (Valorization, Implication and Education) intervention is a multidisciplinary program including physical activity, nutritional, and psychological interventions in pediatric oncology. This study involves one intervention group that will be followed over two years (evaluations and physical activity interventions) and one control group that will participate in only one evaluation. The feasibility of this program will be measured through a comparison between sessions performed and sessions scheduled, while the security will be measured according to the number of reported incidents.
Preliminary Results: An adhesion rate of about 40% despite restrictions and organizational conflicts specific to the hospital context was reported. A minor incident in 1 of 278 sessions performed with 35 children with cancer was observed.
Conclusion: This study is the first to examine the effects of exercise in pediatric oncology, from diagnosis to the expected end of treatment. At this time, our findings show the feasibility of this physical activity program in a safe context. This is an important study in the exercise and oncology field to help patients and their family during and after cancer treatments.
Citation Format: Maxime Caru, Gabrielle Duhamel, Valérie Marcil, Serge Sultan, Caroline Meloche, Isabelle Bouchard, Simon Drouin, Laurence Bertout, Caroline Laverdière, Daniel Sinnett, Daniel Curnier. Feasibility of physical activity in children with cancer: A multidisciplinary program in the context of the VIE study [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr A57.
Abstract A70: Aqueous humor is superior to blood as a liquid biopsy for retinoblastoma
Authors: Xu Liya , Berry Jesse L , Polski Ashley , Jubran Rima , Kuhn Peter , Kim Jonathan W. , Hicks James 
Published: August 2020

Abstract
Purpose: To evaluate whether blood demonstrates similar potential as aqueous humor (AH) to be used as a liquid biopsy for retinoblastoma (RB) and whether tumor-derived cell-free DNA (cfDNA) can be isolated as effectively from the blood as AH.
Methods: AH was extracted via clear corneal limbal paracentesis from RB eyes at diagnosis or during intravitreal injection of chemotherapy. Matched peripheral venous blood samples were drawn. Shallow whole-genome sequencing was performed to assess for cell-free tumor DNA fractions and highly recurrent somatic copy number alterations (SCNAs) in the blood and AH samples.
Results: Seven samples of AH taken at diagnosis and 13 samples at the time of intravitreal injection were compared to matched blood samples. The presence of any detectable SCNA in the AH was 11/20 and 0/20 in the blood (p=&lt;0.001). The median size distribution of cfDNA molecules in the AH was 157.5 bp versus 181.5 bp in the blood (p=&lt;0.001).
Conclusions: The AH appears to be superior to the blood as a source of cell-free tumor DNA for retinoblastoma, thus a better target for development as a liquid biopsy for this cancer.
Citation Format: Liya Xu, Jesse L Berry, Ashley Polski, Rima Jubran, Peter Kuhn, Jonathan W. Kim, James Hicks. Aqueous humor is superior to blood as a liquid biopsy for retinoblastoma [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr A70.