dataesr/scientific-paragraphs-categorization huggingface dataset:
Update on Clinical Trials When our latest Trial Watch dealing with DC-based anticancer interventions was submitted for publication to OncoImmunology (July, 2012), official sources listed 114 recent (started after 2008, January 1st) clinical trials (all statuses included) that would assess the safety and efficacy of this immunotherapeutic strategy in cancer patients. 32 Of these studies, 35 involved DCs loaded ex vivo with purified TAAs, 34 DCs transfected with tumor-derived RNA or engineered to express TAAs, 22 DCs loaded ex vivo with tumor lysates, 9 dendritomes and 14 other DC-based approaches (including in vivo DC targeting). The status of the vast majority of these trials has remained unchanged since, with the exception of NCT00678119, NCT00683241, NCT00722098 and NCT01373515 (all of which have been completed), as well as NCT01216436 (which has been suspended for funding issues) (source www.
clinicaltrials. gov). Preliminary results from NCT01373515, a Phase I/IIa clinical trial investigating the safety and therapeutic potential of DCP-001, a preparation of mDCs obtained from an acute myeloid leukemia (AML)-derived cell line that expresses multiple TAAs (so-called "DCOne" cells), have been disclosed at the meeting of the American Society of Clinical Oncology (ASCO) held last June in Chicago (IL, USA). DCP-001 was well tolerated by AML patients, with most common toxicities being moderate (grade < 2) injection site reactions. In addition, DCP-001 not only elicited robust cellular and humoral immune responses, but also was associated with clinical activity (at least to some extent), warranting the initiation of a randomized Phase II study. 337 To the best of our knowledge, the results of NCT00678119 (testing DCs transfected ex vivo with tumor-derived RNA in prostate cancer patients), NCT00683241 (assessing the clinical profile of DCs pulsed ex vivo with cancer-cell lysates in women affected by ovarian carcinoma) and NCT00722098 (investigating the safety and therapeutic activity of DCs loaded ex vivo with multiple recombinant TAAs in melanoma patients) have not yet been disclosed.
At present (July 2013), official sources list 29 clinical trials launched after 2012, July 1st that would investigate the safety and therapeutic profile of DC-based anticancer interventions (source www. clinicaltrials. gov). The most common approach in this sense is represented by the administration of autologous DCs expanded ex vivo in the presence of one or more recombinant TAAs or peptides thereof (8 trials). Thus, DCs loaded with v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 (ERBB2)-, carcinoembryonic antigen (CEA)-, tumor blood vessel antigen (TBVA)-, or NY-ESO-1-derived peptides are being tested in cohorts of patients affected by breast carcinoma, CRC, melanoma or other solid neoplasms, respectively, either as standalone immunotherapeutic interventions (NCT01730118; NCT01885702) or combined with IL-2 plus autologous lymphocytes genetically engineered to express a NY-ESO-1-targeting T-cell receptor (NCT01697527) or dasatinib, an FDA approved multitarget tyrosine kinase inhibitor  [338] [339] [340] [341] [342]  (NCT01876212).
Along similar lines, the safety and clinical profile of autologous DCs pulsed ex vivo with not better specified TAAs or TAAderived peptides, administered in combination with the hitherto experimental TLR3 agonist Hiltonol  ® 219,343  or with hematopoietic stem cells plus cytotoxic T lymphocytes, are being assessed in advanced or unresectable melanoma patients (NCT01783431) as well as in subjects bearing primary glioblastoma multiforme (NCT01759810) or brain metastases from breast or lung carcinoma (NCT01782274; NCT01782287) (Table  1 ). Seven trials initiated after 2012, July 1st to assess the safety profile and efficacy of DC-based anticancer interventions involve sipuleucel-T. In particular, sipuleucel-T is being tested (invariably in cohorts of advanced, castration-resistant prostate carcinoma patients) in combination with a wide panel of immunotherapeutic interventions, including: (1) various forms of radiotherapy  233, [344] [345] [346]  (NCT01807065, NCT01833208, NCT01818986); (2) ipilimumab, an FDA approved monoclonal antibody targeting cytotoxic T lymphocyte-associated protein 4 (CTLA4)  [347] [348] [349] [350]  (NCT01804465; NCT01832870); (3) glycosylated recombinant human IL-7  227, 230, 351, 352  (NCT01881867); and (4) a DNA-based anticancer vaccine administered together with recombinant GM-CSF  225,227,230,353,354 (NCT01706458).
Five studies have recently been launched to investigate the clinical profile of autologous DCs pulsed ex vivo with tumor lysates. This approach, is being evaluated either as a standalone therapeutic intervention or combined with gemcitabine (an immunostimulatory nucleoside analog)  65, 66, 355, 356  and/or the FDA-approved TLR7 agonist imiquimod,  218, [357] [358] [359] [360] [361]  in cohorts of individuals bearing various forms of sarcoma (NCT01803152, NCT01883518), brain cancer (NCT01808820), melanoma (NCT01753089) or CRC (NCT01671592). Of note, NCT01671592 is an investigational, as opposed to interventional, clinical trial, aimed at followingby magnetic resonance imaging (MRI)-the distribution of DCs loaded ex vivo with tumor lysates upon reinfusion (Table  1 ). Six distinct clinical trials have been launched after 2012, July 1st to evaluate the safety and efficacy of autologous DCs.
Four of these studies involve the reinfusion of autologous DCs expanded ex vivo (in the presence of appropriate maturation signals, but not genetically modified), either as a standalone therapeutic interventions or in combination with Hiltonol ® , to individuals affected by Stage III melanoma (NCT01875653), unresectable pancreatic carcinoma (NCT01677962) or other solid neoplasms (NCT01734564; NCT01882946). In addition, two clinical trials are testing the therapeutic profile of DCs genetically engineered to express a GM-CSF-carbonic anhydrase IX fusion protein or an exogenously activatable variant of CD40, given as single agent or in combination with the chemical CD40 activator, respectively, in metastatic RCC (NCT01826877) and castration-resistant prostate carcinoma (NCT01823978) patients.
Finally, the efficacy of DCs transfected ex vivo with tumor-derived or TAAcoding RNAs, invariably as standalone therapeutic interventions, is being investigated in 3 clinical trials. In particular, DCs transfected with mRNAs coding for Wilms' tumor 1 (WT1) or several other leukemia-associated antigens are being explored as a treatment for AML patients undergoing remission (NCT01686334; NCT01734304), whereas DCs electroporated with not better specified mRNAs (presumably bulk mRNAs derived from neoplastic lesions) are being tested in individuals affected by Stage III/IV melanoma (NCT01676779) (Table  1 ).
7] [108]  Nowadays, several of these DC-based anticancer interventions have entered the clinical phase of development. Official sources list indeed more than 120 clinical trials recently (after 2008, January 1st) initiated to test the safety and efficacy of DC-based anticancer immunotherapy (source www. clinicaltrials. gov). Of these studies, 29 were launched during the last 13 mo, indicating that the interest of clinicians in the therapeutic potential of DCs remains very high. However, with the notable exception of sipuleucel-T, which is currently approved by FDA and other international regulatory agencies for the treatment of metastatic castration-refractory prostate cancer,  110, 362, 363  the clinical progress of DC-based anticancer immunotherapy appears to be problematic, with the majority of strategies failing to proceed beyond Phase II studies.
Acknowledgments Jitka Fucíková works for Sotio a. s. ( Prague, Czech Republic ), which is actively investigating DC-based vaccines in both preclinical and clinical settings. Authors are supported by the  European Commission (ArtForce) ;  European Research Council (ERC) ;  Agence National de la Recherche (ANR) ;  Ligue Nationale contre le Cancer ;  Fondation pour la Recherche Médicale (FRM) ;  Institut National du Cancer (INCa) ;  Associazione Italiana per la Ricerca sul Cancro (AIRC) ;  Association pour la Recherche sur le Cancer (ARC) ,  LabEx Immuno-Oncologie ;  Fondation de France ;  Fondation Bettencourt-Schueller ; AXA Chair for Longevity Research;  Cancéropôle Ile-de-France ,  Paris Alliance of Cancer Research Institutes (PACRI)  and  Cancer Research for Personalized Medicine (CARPEM).
a. As single agent NCT01753089 Sarcoma I I/II recruiting recruiting n. a. n. a. Combined with imiquimod ± gemcitabine NCT01803152 As single agent NCT01883518 Breast carcinoma I II/IIII recruiting Active not recruiting erBB2 n. s. As single agent Combined with CTLs and HSCT NCT01730118 NCT01782274 CrC I/II recruiting CeA As single agent NCT01885702 DCs pulsed with TAAs or TAA-derived Glioblastoma Lung cancer II/IIII II/IIII Active not recruiting Active not recruiting n. s. n. s. Combined with CTLs and HSCT Combined with CTLs and HSCT NCT01759810 NCT01782287 peptides Melanoma II n. a. Not yet recruiting recruiting TBvA n. s. Combined with dasatinib Combined with Hiltonol® NCT01876212 NCT01783431 Combined with IL-2 + autologous Advanced tumors II recruiting NY-eSO-1 PBLs genetically modified to express a NCT01697527 NY-eSO-1-targeting TCr DCs transfected with AML I/II Not yet recruiting Multiple LAAs As single agent NCT01734304 TAA-coding rNA II Not yet recruiting wT1 As single agent NCT01686334 Melanoma II recruiting n.
s. As single agent NCT01676779 I recruiting PAP Combined with ipilimumab NCT01832870 II Not yet recruiting PAP As single agent or in combination with eBrT NCT01807065 Sipuleucel-T Prostate cancer II recruiting PAP Combined with a DNA-based vaccine and GM-CSF NCT01706458 II Active not recruiting PAP Combined with ipilimumab NCT01804465 II Not yet recruiting PAP Combined with SABr NCT01818986 II Not yet recruiting PAP Combined with glycosylated rhIL-7 NCT01881867 n. a. Not yet recruiting PAP Combined with radiotherapy NCT01833208 Abbreviations: AML, acute myeloid leukemia; CeA, carcinoembryonic antigen; CrC, colorectal carcinoma; CTL, cytotoxic T lymphocyte; DC, dendritic cell; eBrT, external beam radiation therapy; erBB2, v-erb-b2 erythroblastic leukemia viral oncogene homolog 2; GM-CSF, granulocyte macrophage colony-stimulating factor; HSCT, hematopoietic stem cell transplantation; IL, interleukin; LAA, leukemia-associated antigens; n.
a. , not applicable/not available; n. s. , not specified; PAP, prostatic acid phosphatase; PBL, peripheral blood lymphocyte; rCC, renal cell carcinoma; rh, recombinant human; SABr, stereotactic ablative radiation therapy; TAA, tumor-associated antigen; TBvA, tumor blood vessel antigen; TCr, T-cell receptor; wT1, wilms' tumor 1. *Started after 2012 July, 1st and not withdrawn, terminated or suspended at the day of submission (source www. clinicaltrials. gov).
Statistical analysis A database was built using Excel 7. 0 (Microsoft) software. MRI findings and CSF/serum HP10 levels were recorded. Statistical analysis was made using SPSS 10. 0 (Microsoft), Epidat 3. 0 and SAS 9. 0 softwares. Parametric statistics (mean and SD) were calculated. Kappa coefficient (k) and 95% confidence intervals were calculated to evaluate the qualitative agreement between HP10 results in CSF and sera and between institutions. This coefficient varied between 21 and +1. The closer the value is to1, the stronger the agreement  [20]. Generalized Estimating Equations (GEE) analysis  [21]  was performed in order to confirm agreement taking into account repeated observations and variability of period of time between appointments. Results.
Over the past ten years technologies for generating, maintaining and using 3D geo-information have matured. For national mapping agencies one of the challenges is how to best extend 2D data into 3D data, making best use of research results and available technologies. Some mapping organisations are making serious progress. The question addressed in this paper is how research results achieved in the past ten years are applied in practice and what research problems remain. In addition, the paper explores the potentials of the OGC 3D standard (i. e. CityGML) for 3D national mapping and what developments are further required to make the standard better fit for this purpose. The main conclusions of the paper are that 3D data is more and more available but still suffers from a low level of usage (mainly visualisation) and standards and formats based on CityGML have been stabilised although software support is still in the early stage.
INTRODUCTION Over the past ten years technologies for generating, maintaining and using 3D geo-information have matured. Many local governments have 3D models of their area, a large number of companies are providing services for creating or disseminating 3D models, and universities and research organisations are investigating 3D technologies, from capture to data services. In addition, the Open Geospatial Consortium defined the 3D standard CityGML 1. 0 in 2008 and released a 2. 0 version in 2012  (OGC, 2012). This has grown to a well-established standard for 3D geo-information. CityGML originated in academia in Germany (Bonn, TU Berlin) and was originally defined as an exchange format. But it is also -and perhaps more importantly-an information model for representing 3D spatial objects. Although it started as a standard to model objects that occur in cities, the current version (2.
0) has been expanded and now supports a variety of objects in landscape and city models. Many projects use CityGML for 3D modelling. For example North-Rhine Westphalia in Germany has been the first state that provides a statewide 3D model consisting of 3D roads, railways, DTM, and 3D buildings employed for noise dispersion mapping  (Czerwinski et al 2006; 2007). Another important achievement in CityGML implementation is the extension of the German national cadastre model ALKIS by 3D building models. In this project a CityGML profile has been defined and most states in Germany provide 3D building models according to this profile. In addition INSPIRE data specifications for buildings contain a 3D building profile in line with the CityGML specifications for buildings. Finally, different Application Domain Extensions have been developed.
Some examples are noise (as used in the German state North-Rhine Westphalia and as documented within the CityGML specification), utility networks  (Becker et al, 2010; 2013) , real estate management, robotics, building information models (BIM), and hydrography (see  CityGML, 2013). It is clear that 3D applications are becoming increasingly important and therefore production of 3D information by governmental organisation gets more and more mandatory. For national mapping agencies, who have a long history in maintaining and incremental updating countrywide 2D-datasets, the major challenge is how to best convert this 2D data into 3D data, while supporting the established process of continuous incremental updating and making best use of research results and available technologies. Some mapping organisations are already making serious progress in this step (i.
3D MAPPING AT ICC: 3D DATA FOR TOPOGRAPHIC PRODUCTS The Institut Cartogràfic de Catalunya (ICC) is the regional mapping agency of the Government of Catalonia. From its creation in late 1982, the ICC has focused improving the cartographic production workflows. Topographic data, ranging from scales 1:1000 to 1:25. 000, are mainly collected using photogrammetric systems and stored using 2. 5D data models. Elevation models are derived from these models. Smaller scales such as 1:50. 000 and 1:250. 000 are collected in 2D, digitized on top of orthophotoimages. Since 2002, LIDAR systems are an additional source for elevation data. A full coverage of Catalonia is available with 1point/2m2 density. ICC products, including data, metadata and specifications, are distributed free-of-charge.
3D Topographic Data in urban areas The topographic data set at 1:1000 scale (CT-1M) is the most detailed data covering the urban areas and the areas planned for urbanization, a total surface of 330. 000 hectares. The accuracy of this product is 20 centimeters for X and Y and 25 centimeters for height. The data is compiled using photogrammetric systems, completed by data surveyed on the field, stored in an ORACLE database and distributed as geoservices and several GIS and CAD formats, including KMZ for buildings (see Figure  1 ). The updating cycle is between 4 and 6 years, depending on the number and importance of the changes on the territory. The Topographic Database at 1:5000 scale (BT-5M) is the most detailed database that covers complete Catalonia. The data is compiled using photogrammetric systems according to a 2.
5D data model and stored in an ORACLE database. The accuracy is 1 meter for X and Y and 1. 5 meters for the height. During the stereoplotting process all the features required to generate a digital terrain model (DTM) and a digital surface model (DSM) are compiled together with the topographic objects (Figure  3 ). The updating cycle is 5 years over all the country and more frequently over the most dynamic areas, located mainly in the coast.
The Topographic Database at 1:25. 000 scale Although from the beginning of 2000's a complete coverage of BT-5M was available, the customers were asking for a database at smaller scale for new GIS applications and mapping. This database should be manageable, like the 1:50. 000 database, but with the topographic information as detailed as possible, like the 1:5. 000. Moreover, elevation data was considered essential for visualization and analysis applications. A new topographic database at 1:25. 000 scale and 2. 5D (BT-25M) was designed to fulfill these user requirements. The existence of a production program for the BT-5M and the experiences at the ICC in implementing generalization workflows, allowed to start producing the first version of the BT-25M using generalization processes in the year 2003.
Comparing with previous ICC generalization experiences, the workflow entailed two challenges: to obtain a topographic database, not only a map, and to generalize 2. 5D data instead of 2D data (Figure  4 ). The complete coverage was finished in 2011 and, nowadays, the database is being updated independently of the original database, because the updating cycle planned for the BT-25M will be approximately 2 years, much shorter than the 5 years updating cycle of the BT-5M.
Work in progress The first line of the 3D work in progress is focused in the enrichment of the CT-1M data, adding the inclined roofs for obtaining a LOD2 city models. After some tests on commercial software for obtaining inclined roofs automatically, based on image correlation and building boundaries, the results are promising although manual tasks will be required to refine them. The second line of 3D work is the use of LIDAR data to improve the elevation data derived from the BT-5M, mainly in dense forests areas, where ground is not visible in the aerial images. Although the accuracy of LIDAR data is 0. 5 m in X and Y and 6-10 cm in Z, it must be taken into account that in cliffs and areas of high slope LIDAR data requires fine filtering. Moreover, the potential problems of incoherence between planimetric features and LIDAR data will be analyzed, for example in talwegs.
The third line of work is related to maintenance and updating of the information, crucial for optimizing the production costs. The related tasks in development are the coordination with municipalities and other government organizations to share information to speed the change detection. Other line of work is the analysis of the compatibility between ICC data models and other models and standards, as CityGML and INSPIRE. Finally, aspects related to dissemination of the information, are also under study. Although there is a huge potential of city model applications (urban planning, telecommunications, energy, environment, smart cities, simulations, etc. ), visualization is the most common while the other ones are not yet enough developed. A 3D viewer for ICC data, considering continuous zoom using the CT-1M, BT-5M and BT-25M information, is currently in development.
3D MAPPINT AT ORDNANCE SURVEY: FROM 2D TO 3D -EXPERIENCES AND CHALLENGES As the National Mapping Agency for Great Britain, Ordnance Survey's products include address data, digital terrain models (DTMs), road networks, imagery and topographic mapping (vector and raster), including the flagship topographic vector mapping product, OS MasterMap ® Topography Layer. With the exception of the DTM products, Ordnance Survey's portfolio is largely 2D-centric. However, many customers are using 2D data to help make decisions that are inherently threedimensional in nature; for instance, planning and consulting on urban change, asset management, civil contingency planning and risk assessment. This section outlines how OSGB anticipates meeting their customers' 3D needs. It will discuss issues that are being faced when moving towards a 3D-centric view.
A 3D future for Ordnance Survey? The long-term plan is to '3D-enable' the core databases, products and services. This will involve three broad types of change (see Figure  5 ): • Creating a new generation of elevation models (completed) • Adding ground height values to 2D vertices and features in the existing 2D datasets, including topographic features and routing networks (underway) • Generating elevations for features that extrude from the ground surface, including buildings, structures and vegetation.
Principle Narrative Survey standards Data will be captured to defined standards of geometric and attribute accuracy Maintained Features will be revised and updated throughout their lifecycle through a combination of continuous and cyclic processes Nationally consistent Equivalent geographies will (over time) be published to an equivalent specification Intelligent The data will enable spatial query and analysis Interoperable The data will be usable in association with both Ordnance Survey and external datasets. Accessible Products will be made available in formats and delivery methods which encourage adoption for sustained application.
Technical barriers Firstly, automated data capture techniques are preferred for minimising time and cost. This is especially relevant when scaling up to a city or national level. 3D data must also be captured during the same revision cycles as the existing 2D datasets in order to ensure synchronicity and interoperability. Since extensive use of photogrammetric techniques is being made for 2D capture, there is an obvious incentive to use similar techniques for 3D data capture to ensure this. Secondly, data capture trials have shown that there are issues related to matching up of existing 2D footprints and 3D roof shapes. The existing 2D capture specification is oriented towards building function rather than roof form. Thought needs to be employed on how the two representations can be brought closer together.
Organisational barriers Ordnance Survey has for over 200 years produced 2D data. This has resulted in a certain level of learned behaviour and in a legacy of products defined in terms of 2D data specifications and representations. Consequently a process of review is necessary internally in order to gain a better understanding of 3D in its end-to-end sense, from capture to customer. This 'learned behaviour' idea can also be extended to our customers. For most of OS customers 3D is a very new concept operationally. The experience of OS is that customers have a generally low level of experience and understanding of the implications and cost of using 3D data.