dataesr/scientific-paragraphs-categorization huggingface dataset:
Background Sharing of -omics data has become the default modus operandi in recent years, with many funding sources and journals requiring authors to deposit their data in public repositories. This has led to a wealth of available datasets for in silico analysis or validation of new findings. To date, over 65,000 studies were deposited in the NCBI Gene Expression Omnibus (GEO) of which more than 1200 relate to breast cancer. However, these repositories are accompanied with minimal analysis and/or limited built-in visualization features in addition, offline analysis is relying on elevated bio-informatics skills. In order to make these datasets more accessible and interactive, we developed a web application called gene expression browser or GXB  [1]. Methods As a pilot project, we uploaded the GEO datasets we recently used to validate breast cancer immune subtypes to the GXB application and annotated the datasets collating data from the GEO database entries, the matching publications and added our own immune gene clustering assignments  [2, 3].
Results A total of 2178 samples were imported as part of 14 GEO datasets, 1728 of which were used in our validation set. One dataset (GSE9151) was deposited in GEO in an incompatible format and had to be reprocessed from the raw CELL files into a normalized expression matrix. Adding group sets for clinical features, immunological gene clusters and generating matching gene rank lists will allow the users to quickly visualize differentially expressed genes. The addition of extra overlay data will enable the user to investigate correlations between phenotypic features. An example of the visualizations available in this application is demonstrated in Fig. 29.
Results We identified an average of 680 potential neoepitopes per patient based solely on WGS data. To further refine and select high quality neoepitopes we restricted these neoepitopes based on gene expression yielding an average of 304 expressed neoepitopes per patient. We predicted each patient's HLA typing using only omics data, which we then used to predict HLA-expressed neoepitope binding analysis resulting in an average of 11 high-quality tumor specific neoepitopes per patient. We identified few recurrent neoepitopes that were bound and expressed, indicating the need for a personalized medicine approach. Conclusions Within the TCGA dataset, the majority of neoepitopes among patients with breast cancer were unique to each patient. Rarely within subsets of breast cancers such as HER2+, do we identify neoepitopes that are shared between patients.
Results Using the 2CT genome-scale perturbation screen in melanoma cells, we identified and validated multiple genes whose loss impaired the effector function of T cells. Moreover, we uncover a group of core genes from these screens that correlates with cytolytic activity across the majority of the cancer types, reflecting context independence of these genes in the modulation of inherent T cell responses in multiple cancers. This dataset can be utilized to stratify patients for T cell based immunotherapies, and also for studying emergence of novel immune escape mechanisms.
Background High dose IL-2 (HD IL-2) can provide durable responses in patients with metastatic melanoma (mM) and metastatic renal cell carcinoma (mRCC). PROCLAIM SM [http://www. proclaimregistry. com] is an IL-2 registry that captures real-world patient population survival and outcomes. Herein, we report on patient experience sequencing HD IL-2 with immune checkpoint blockade (ICB) and/or targeted therapy (TT) in mM and mRCC. Methods Patients were prospectively enrolled into the registry as of 2011 and must have received at least one dose of HD IL-2. Statistics and survival analysis were performed on datasets as of December 17, 2015.
In mRCC, survival based on TT or ICB after HD IL-2 was analyzed (Table  3 ). Survival of patients receiving HD IL-2 as first line with no post therapy was also determined (Table  3 ). Conclusions This analysis of the national IL-2 registry suggests that HD IL-2 continues to be a valuable treatment option for eligible mM and mRCC patients. Attainment of SD is clinically relevant and contributes to HD IL-2's survival benefit. Support for investigation of HD IL-2 in combination or sequence with ICB is warranted. Trial Registration ClinicalTrials. gov identifier NCT01415167.
Results EnAd induced up-regulation of surface activation markers and induced the production of pro-inflammatory cytokines. Further mechanistic experiments, comparing the effects of EnAd to those of Ad5 indicated that the activation was selective for EnAd, was particle-mediated and dependent on CD46 binding. In order to understand the functional implications downstream of these interactions, T cell activation and phenotype was assessed using an allogeneic mixed lymphocyte reaction approach. EnAd-treated DCs selectively stimulated stronger T cell responses, including enhanced IFNg production. The data supports EnAd as a good candidate OV for steering the response of T cells activated within the tumor towards a Th1 phenotype for enhanced effector responses. Conclusions Thus, as well as its potent oncolytic properties, EnAd particles may also function in the tumor microenvironment to help drive functional adaptive immune responses by inducing proinflammatory phenotype APCs, which should also synergize effectively with other immunotherapy strategies.
In order to further substantiate our findings, we analyzed an independent cohort of non-T cell inflamed bladder cancers. Methods Ninety-three samples were analyzed from a validation data set (GSE 31684) with gene expression profiling. Affymetrix microarray files were downloaded from the GEO database and preprocessed to generate normalized gene expression values for 20,390 genes. Consensus clustering of samples was conducted using 725 genes from our prior TCGA analysis, and repeated using a refined 160 gene set developed across multiple cancer types by Methods previously described. Immune subtypes were called based on gene expression. Differentially expressed genes were filtered by FDR-adjusted Pvalue < 0. 01 and fold change ≥ 1. 5.
Here we report safety/tolerability, pharmacokinetics, pharmacodynamics, and preliminary clinical efficacy results from these trials. Methods During escalation in NCT01775631, patients with relapsed/refractory B-NHL received urelumab at 0. 1 or 0. 3 mg/kg or a flat dose of 8 mg (equivalent to 0. 1 mg/kg in an 80-kg patient; initiated based on available pharmacokinetic and safety data) Q3W plus rituximab 375 mg/ m 2 QW (4 doses); during expansion, patients with relapsed/refractory diffuse large B cell lymphoma (DLBCL) or follicular lymphoma (FL) were treated with urelumab 8 mg plus rituximab. The NCT02110082 study evaluated urelumab (0. 1 mg/kg or 8 mg Q3W) plus cetuximab (400 mg/m 2 on week 1 and 250 mg/m 2 Q1W thereafter) in patients with metastatic CRC or SCCHN. Primary endpoints were safety/ tolerability.
Trial Registration ClinicalTrials. gov identifier NCT01775631 and NCT02110082. P260 ATM is essential for the radiation-induced upregulation of the immunosuppressive cytokine activin-A by breast cancer cells Claire I Vanpouille-Box, Silvia C Formenti, Sandra Demaria Weill Cornell Medicine, Department of Radiation Oncology, New York, NY, USA Correspondence: Claire I Vanpouille-Box (clv2002@med. cornell. edu) Journal for ImmunoTherapy of Cancer 2016, 4(Suppl 1):P260Background Activin A (actA) is a member of the transforming growth factor beta (TGFβ) superfamily. Recent evidence suggests that actA may facilitate tumorigenesis in part by suppressing immunity in the tumor microenvironment[1]. Treatment-induced DNA double-strand breaks.
58). Responses were more durable and of highest magnitude for IFA V6. IVS CD8 responses and ex vivo CD4 responses were also improved with addition of IFA. Conclusions LPS is a safe and effective vaccine adjuvant when combined with IFA; the optimal biologic dose may be 100-400 EU. All regimens were deemed safe. Despite recent concerns about IFA, this study demonstrates that in humans, IFA enhanced magnitude and durability of T cell responses to peptide vaccines when added to TLR agonists. Thus, combination strategies with IFA and LPS and/or pICLC offer promise for next generation vaccines. Trial Registration ClinicalTrials. gov identifier NCT0158535. P353Long-term follow-up of Vigil (DNA engineered bi-shRNA furin GMCSF plasmid/autologous tumor) in recurrent metastatic Ewing's sarcoma (EWS) Maurizio Ghisoli 1 , Minal Barve 1 , Robert Mennel 2 , Gladice Wallraven 3 , Luisa Manning 4 , Neil Senzer 5 , John Nemunaitis 5 1 Mary Crowley Cancer Research Centers, Texas Oncology, P.
Multiplex immunohistochemistry (mIHC) allows for automated quantitation of phenotypes and spatial distributions of immune cells within formalin-fixed paraffinembedded (FFPE) tissues. In early stage melanoma, it has been established that tumor infiltrating lymphocytes (TILs) confer a favorable prognosis but assessment of TILs is subjective and the correlation has not been robust enough to incorporate into American Joint Committee on Cancer (AJCC) guidelines. Methods In order to test whether mIHC can improve on the accuracy of TIL quantitation for the purpose of biomarker development, we screened databases at the Herbert Irving Cancer Center (HICC) at Columbia University for early stage melanoma patients with available FFPE primary melanoma tissue and documented clinical follow up. We identified a preliminary population of 20 stage II-III melanoma patients diagnosed between 2000 and 2012, with characteristics shown in Fig.
Acknowledgements Funded by  NCI  Contract  HHSN261200800001E. 1 Thoracic  and  GI Oncology Branch, National Cancer Institute ,  Bethesda, MD ,  USA ; 2  Department of Medicine, Division of Hematology Oncology, UCSF ,  San Francisco , CA, USA; 3 H. Lee Moffitt Cancer Center, Tampa, FL, USA; 4 Gastrointestinal Oncology and  Mesothelioma Programs ,  Section of Hematology/Oncology, University of Chicago, Chicago, IL, USA; 5 Penn Prebyterian Medical Center, University of Pennsylvania, Philadelphia, PA, USA; 6 Aduro Biotech, Inc. , Berkeley, CA, USA ; 7  Oregon Health & Science University , Portland, OR, USA Correspondence:  Somayeh Honarmand  (shonarmand@aduro. com)Journal for ImmunoTherapy of Cancer 2016, 4(Suppl 1): P253  Acknowledgements Supported by  DOD BCRP post-doctoral fellowship   W81XWH-13-1-0012.
Acknowledgements Medical writing services provided by  Brian R. Haas, PhD , were funded by  Dendreon Pharmaceuticals, Inc. Trial Registration  NCT01431391  and  NCT01981122. 1  Meharry Medical College, Nashville , TN, USA; 2  Medical College of Georgia, Augusta, GA, USA ; 3  Meharry Medical College School of Medicine , Nashville, TN, USA; 4  National Cancer Institute-Frederick, Frederick, MD, USA ; 5  CIP, Center for Cancer Research, BSP ,  Leidos Biomed Research Inc, National Cancer Institute-Frederick, Frederick, MD, USA Correspondence :  Anil Shanker  (ashanker@mmc. edu)Journal for ImmunoTherapy of Cancer 2016, 4(Suppl 1): P332  Acknowledgements We acknowledge the  MDACC core facility NCI Support  Grant  P30CA16672. Acknowledgements Funding from 2014  Movember Prostate Cancer Foundation Challenge Award and Madison Vaccines, Inc.
Trial Registration ClinicalTrials. govidentifier  NCT02499835. Acknowledgements This work was supported by the  European Union 's  Seventh Framework Programme  under Grant Agreement No. 602705. Trial Registration ClinicalTrials. govidentifier NCT02390063. Acknowledgements  T32  grant  AI007505 , the  American Cancer Society  grant  RSG LIB-114645 ,  Cancer League of Colorado , The  University of Colorado Lung Cancer   SPORE Career Development Award   5P50CA058187-20 , and  CCSG CA 046934 , and  CCTSI UL1 TR 001082. Acknowledgements Funding for the study was provided by the  Cancer Research Society. Acknowledgements HJLCT Melanoma Research  Award  2010 ,  Fulbright Research Grant  No:  1214104/2014 ,  BioIncept LLC  sPIF (proprietary). Acknowledgements SK acknowledges support from the  OHSU Knight Cancer institute and Collins Medical Trust.
Acknowledgements Gene expression data from melanoma metastases were provided by  Steven A Rosenberg (NCI). Some results here are based upon data generated by the  TCGA Research Network : http://cancergenome. nih. gov(Cerami, et al. , PMID 22588877; Gao J, et al. , PMID 23550210). 1  University of Pittsburgh , Pittsburgh, PA, USA; 2  Magee-Womens Research Institute, Ovarian Cancer Center of Excellence , and  Peritoneal/Ovarian Cancer Specialty Care Center, Hillman Cancer Center ,  University of Pittsburgh, Pittsburgh, PA, USA; 3 Department of Surgery; University of Pittsburgh Cancer Institute; Department of Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, PA, USA Correspondence :  Marie-Nicole Theodoraki  (marie. nicole. theodorakis@gmail. com)Journal for ImmunoTherapy of Cancer 2016, 4(Suppl 1):P413 Acknowledgements KHY received an  ASCO Young Investigator Award  and an  RSNA   Research Seed Grant  which funded this work.
Our results demonstrate potent ATPP-mediated anti-tumor efficacy, independently of the MHC class I antigen processing machinery, by loading tumor cells with viral peptide antigens and redirecting virusspecific cytotoxic T cells against cancer. Trial Registration ClinicalTrials. gov identifier NCT01609556, NCT02631876, and NCT02606305. P304 CovIsoLink, a new enzymatic conjugation for the development of innovative antibody drug conjugates Sandrine Valsesia-Wittmann 1 , Eva Sivado 1 , Vincent Thomas 2 , Meddy El Alaoui 1 , Sébastien Papot 3 , Charles Dumontet 4 , Mike Dyson 5 , John McCafferty 5 , Said El Alaoui 2 1 Centre Léon Bérard, innovations in immunotherapy platform, Rhone-Alpes, France; 2 Covalab, Villeurbanne, Rhone-Alpes, France; P303 3 IC2MP, Poitiers, Limousin, France; 4 CRCL, Lyon, Rhone-Alpes, France; Treatment of tumor cells with mirvetuximab soravtansine, a 5 IONTAS, Cambridge, England, UK FRalpha-targeting antibody-drug conjugate (ADC), activates Correspondence: Sandrine Valsesia-Wittmann monocytes through Fc-FcgammaR interaction and immunogenic (sandrine.
Conclusions These results demonstrate that INO-3112 DNA-based immunotherapy can induce detectable immune responses in peripheral blood and tumor tissue in subjects with HPV associated HNSCCa. Trial Registration ClinicalTrials. gov identifier NCT02163057. ResultsAs of August 1 2016, accrual has been completed with 22 enrolled subjects. Cohort 1: n = 6, Cohort 2: n = 16, 20 males, median age 57. 5 years; base of tongue cancer = 10, tonsil cancer = 12; never smoker = 10. Six subjects in Cohort 1 received at least one dose of INO-3112 on average 14 days (.
Conclusions Importantly, our findings are clinically relevant since HNC patients that were treated with cetuximab single agent on a neoadjuvant trial (UPCI #08-013, Trial Registration ClinicalTrials. gov identifier NCT01218048. P379 Direct oncogene-targeted cancer killing and selective tumor Treg killing through the TNFR2 receptor via dominant antibody antagonists Heather Torrey, Toshi Mera, Yoshiaki Okubo, Eva Vanamee, Rosemary Foster, Denise Faustman Massachusetts General Hospital/Harvard Medical, Boston, MA, USA Correspondence: Denise Faustman (faustman@helix. mgh. harvard. edu) Journal for ImmunoTherapy of Cancer 2016, 4(Suppl 1):P379.
Obviously, the performance achieved so far in terms of accuracy, scalability and ease of operation leaves plenty of room for improvement. There are still a great number of methods to explore, and more to invent in the fields of image processing and machine vision. We deliver here an original image processing workflow, BioEmergences, in the form of standalone software. Although optimized for MLSM data and fast cell movements in gastrulating zebrafish embryos, it generally performs well on 3Dþtime imaging data without heavy requirements in terms of spatial and temporal resolution, or signal-to-noise ratio. In addition to the reconstruction of the cell lineage branching process, the BioEmergences workflow includes segmentation algorithms for cell nucleus and membrane shapes. These are based on the 'subjective surface' method, which can complete cell contours from heterogeneous fluorescent membrane staining  19.
The standalone version of the workflow can be operated through a graphical user interface, and its output data are connected to Mov-IT, a custom-made interactive visualization software. Alternatively, our web service offers users customized assistance and fast processing on computer clusters or on the European Grid Infrastructure (EGI), together with the possibility to explore a large parameter space for the optimization of results (see Methods to request access). We demonstrate the reconstruction and analysis of six digital embryos from three different species. All the data obtained, raw and reconstructed, is made available to the community. The BioEmergences workflow is compared with eight other software tools from four different providers on the basis of 'gold standard' data sets obtained by manual validation and correction of cell lineages.
2 ). The BioEmergences standalone pipeline produces reconstructed data that can be directly displayed by the interactive visualization software, Mov-IT (Methods). By superimposing reconstructed data on raw data, Mov-IT adds visual inferences to create an 'augmented phenomenology'. This allows the user to control data quality, measure the error rate, easily correct cell detection and tracking errors, and investigate the clonal history of cells and their behaviour. The automated tracking of cells from 4D image data sets across whole living embryos involves a difficult trade-off between interdependent variables: signal-to-noise ratio, spatial and temporal resolution, imaging depth and cell survival. Microscopy techniques for in vivo and in toto imaging of developing organisms are evolving rapidly.
This is achieved by repeated random trials of link modification, and validation of possible changes according to a cost function, based on a weighted sum of contributing terms and a 'temperature' parameter. The last step uses simulated annealing to link childless and motherless cells to the tree in an acceptable way, leaving open the possibility to make a posteriori changes in the detected nuclei. Visualization and validation. After processing, each step of the reconstruction can be interactively visualized and analysed with the Mov-IT software. Developed to address the needs of biologists investigating the potential of in silico embryology based on 3Dþtime microscopy imaging, Mov-IT allows easy validation and correction of nucleus detection and cell lineage by superimposing reconstructed data on raw data.
To this aim, it provides a complete set of tools including 3D volume rendering, 2D orthoslice views, cell lineage and segmentation display. The Mov-IT software was used to validate the reconstruction of our six specimens' cell lineage trees. The sea urchin (Pl1,2) and ascidian (Pm1,2) data sets were extensively checked and curated, producing quasi error-free digital specimens (gold standards) over an average of 30,000 temporal links. The fish data sets (Dr1,2) were only partly checked because of their large number of cells. More than 80,000 tracking links and 1,200 cell divisions were validated and, when necessary, corrected in the data set Dr1 chosen to establish our standard validation protocol (Fig. 4a-d , Methods, Supplementary Movies 7, 8 and 9). The performance of our automated workflow on data set Dr1 was evaluated on three processing outputs: nuclear centre detection, linkage (by tracking cells one time step in the past) and mitosis detection.
03%). The performance on small organisms, sea urchin and ascidian, was close to the gold standards for the best part of the images. Cell detection and tracking were occasionally poorer, depending on the image quality, essentially the signal-to-noise ratio, which degraded with imaging depth. The relevance and usefulness of the BioEmergences reconstruction workflow are demonstrated by comparing its outputs with those obtained on the same dataset Dr1 using state-of-the-art commercial and open-source software. Eight image processing tools from four different providers were deemed suitable to handle gigabytes of time-lapse data. Their performance was tested on the detection of nuclear centres, links and cell divisions in several time intervals (Fig. 5 , Methods and Supplementary Table  1 ). Based on measures of TP rates, called 'sensitivity', and FP rates, our methods produced the best results in every category.
In particular, BioEmergences had the lowest rate of false linkage at 1% (Fig. 5h , column e). It also obtained an average mitosis sensitivity of 67% against 13% for Amat et al. and 0% for the rest (Fig. 5h, column c ), meaning that the other tools were actually not designed to join lineage branches through the detection of divisions. Our software and Amat et al. 's software were the only ones allowing the linkage of one mother cell at time step t to two daughter cells at time step t þ 1. In essence, mitosis detection is a special task that only two packages among the nine that we tested were able to solve. Typically, it is at the time of anaphase and telophase that an algorithm can detect two separate nuclei, and as soon as it does it must also link them back to their mother. If this is not accomplished, the lineage tree will lack a junction.
Discussion The BioEmergences reconstruction pipeline, accessible through a simple graphical user interface, was designed to run as quickly and efficiently as possible from the acquisition of microscopy images to the display of cell lineage and cell segmentation aligned with raw data. Although the standalone version was crafted for convenient processing of small data sets on a laptop computer, there is no size limit on the data that can be uploaded to the BioEmergences web service through iRODS, an open-source data management software and the OpenMOLE engine  14  for data processing on the EGI. The concept of 'augmented phenomenology', coined to describe the overlay of raw and reconstructed data required for validation, correction and analysis, is fully exploited using the custom-made Mov-IT software.
All the results led to the conclusion that the BioEmergences workflow achieved the best performance on standard data produced by MLSM imaging with a temporal resolution chosen to explore either a small specimen (sea urchin or tunicate embryo) or up to one-third of the zebrafish gastrula. The software provided by Amat et al. was the next best, but its performance dropped faster than BioEmergences with the increase in cell density and tissue thickness. The cell tracking pipeline delivered here should be useful for a large variety of model organisms that have adequate optical properties to allow the acquisition of 3Dþtime data sets, including a channel for stained nuclei. The requirements in terms of spatial and temporal resolution and signal-to-noise ratio are easily fulfilled with commercial microscopy setups, either MLSM or SPIM.
The detection of cell nuclei is a critical step, as it is used not only for cell tracking but also for nucleus and membrane shape segmentation, which must be performed on validated nuclei to avoid major errors but is computationally expensive. Although the standalone software performs well on a few selected cells, full-scale shape segmentation can be achieved in a reasonable amount of time only on a computing cluster such as the one accessible through the BioEmergences web service. Segmentation output can also be verified with Mov-IT, but its quantitative validation remains an issue  35. The public availability of the BioEmergences platform and its application to the embryogenesis of model organisms is intended to open the path to in silico embryology based on digital specimens. We illustrate this ambition with fate-map studies.