dataesr/scientific-paragraphs-categorization huggingface dataset:
Acknowledgments We wish to thank  Christophe Flaudrops  from the mass spectrometry platform of the IFR48 of  Marseille  for mass spectrometry analyses,  Bernard Chetrit  from the  Datacentre IT and Scientific Computing of CRCM (DISC)  platform for IT support,  Martin Billeter  and  Roberto Cattaneo  for reagents,  Laurent Roux  and  Dan Kolakofsky  for helpful suggestions, and  Karen Da Cunha  for technical help. We used the qPCR ( B. Blanquier ) facilities of the  SFR Biosciences Gerland-Lyon Sud  ( UMS344/US8 ).
This work was carried out with the financial support of the  Agence Nationale de la Recherche , specific programs " Physico-Chimie du Vivant " ( ANR-08-PCVI-0020-01 ), and " ASTRID " ( ANR-11-ASTR-003-01 ). JE and LMB were supported by fellowships from the  Fondation pour la Recherche Medicale (FRM). MD was supported by a PhD fellowship from the  French Ministry of National Education, Research and Technology. The.
Some of the samples were from West Papua, a former Dutch colony currently administered by Indonesia  [27, 28]  that has no control over its own natural resources  [29]. For equitable sharing of results and knowledge, the data produced in the course of our study will be made accessible from the following open-access repositories: Hal-IRD (http://www. hal. ird. fr/; hal@ird. fr), GenBank (http://www. ncbi. nlm. nih. gov) [30] ,   S1 ). Individuals were identified to species according to present revision, from either their COI or cytochrome b gene sequence. Roman numbers I-VIII designate the haplogroups or clades reported previously  [19, 23] , four of which have since been described or redescribed  [24]  (Table  1 ). Surface of symbol (circle or triangle) proportional to sample size. A. and DIPnet (http://www.
Sampling A total of 362 individuals, including 341 blue-spotted maskray and 21 New Caledonian maskray N. trigonoides, were utilized in the present study. This total includes 203 individuals whose CO1 or cytochrome b gene sequences were compiled from either the literature  [14, 16, 17, 19, [31] [32] [33] [34] [35] [36] [37] [38] , the BOLD barcode database, the Cryobank DNA-barcode database (http://cryobank. sinica. edu. tw/chi/), or the GenBank nucleotide-sequence database; and 159 new individuals sampled from local fish-landing places throughout the Indo-Malay archipelago, in eastern Africa, and in New Caledonia. All individuals included in the present survey are listed in Supplementary Table  S1 , along with sampling details, GenBank accession numbers, voucher specimen details, and references.
Genetic data analysis Nucleotide sequences, including those obtained in the present study, and homologous sequences retrieved from the BOLD, Cryobank, and GenBank databases (see Supplementary Table  S1 ) were aligned using BIOEDIT  [42]. Four datasets were analysed: (1) the CO1 gene sequence dataset, consisting of 330 blue-spotted maskray and N. trigonoides sequences aligned over a maximum length of 722 base pairs (bp); (  2  The phylogeny of concatenated CO1 + cytochrome b gene haplotypes was inferred by using the maximumlikelihood (ML) method under MEGA6  [43]. The most likely nucleotide-substitution model, which was determined according to the Bayesian information criterion, was the Tamura-Nei model  [44]  where a discrete Gamma distribution (G = 0. 76) was used to model evolutionary rate differences among nucleotide sites and invariable sites were allowed.
The ML tree was rooted by choosing New Caledonian maskray N. trigonoides as outgroup  [16]. The robustness of nodes in the tree was tested by bootstrap resampling. The CO1 and cytochrome b gene sequence datasets (Supplementary Table  S1 ) were used separately to assign individuals that were sequenced at only one of either locus to a clade uncovered from the phylogenetic reconstruction described above. For this, an ML tree was constructed using each of the two datasets under MEGA6 and the assignment of a haplotype to a clade was determined visually from its relative position on the tree.
Delineation of cryptic species The Automatic Barcode Gap Discovery (ABGD) algorithm proposed by Puillandre et al. [45]  was used to identify gaps in the distribution of pairwise nucleotide distances. The ABGD algorithm detects the largest significant gap in the distribution of pairwise nucleotide distances and uses it for partitioning the dataset. Gap detection is then recursively applied to previously obtained groups to get finer partitions until there is no further partitioning  [45]. The ABGD analysis was run on a matrix of 127 CO1 + cytochrome b gene sequences, trimmed to a core length of 1415 bp. Kimura's  [46]  twoparameter substitution model was selected and the minimum barcoding gap width was set to 1%. Branch lengths between species are determined by speciation and extinction rates whereas branch lengths within a species reflect coalescent processes at the level of populations  [47].
This results in the distinction of species when mitochondrial clades are substantially deeper than the coalescent haplogroups at the extremities of the tree. We ensured that each of the previously identified deep mitochondrial clades was genetically distant from its nearest neighbour by several times the mean intra-clade distance. For this, pairwise intra-clade and betweenclades genetic distances were estimated on the concatenated CO1 + cytochrome b gene sequence matrix using MEGA6. To delimit potential cryptic species, we applied the general mixed Yule-coalescent (GMYC) algorithm  [47]  as implemented in the program SPLITS under R  [48, 49]. This algorithm uses an ultrametric tree to differentiate branching patterns consistent with coalescent vs. speciation processes, which provides a threshold time for the transition between populational and species-level processes.
We selected the single-threshold option. The ultrametric tree was constructed using BEAST v. 1. 7  [50]  based on the same matrix (127 individuals Â 1415 bp) as that used for the ABGD analysis. Outgroup N. trigonoides was excluded from the analysis, which focused on the blue-spotted maskray exclusively. A non-calibrated relaxed lognormal clock, and a constant coalescent tree were assumed. The model of nucleotide substitution was TN93 + G + I (see Section 2. 4). Ten million generations of Markov-Chain Monte Carlo analysis were run, of which we sampled a total of 10,000 genealogies. Length of burn-in was determined by visual inspection of traces in TRACER v. 1. 5  [50]. A single analysis was run, for which convergence was reached rapidly. The TREEANNOTATOR v. 1. 7. software  [50]  was used to produce the final tree, based on maximum clade credibility and mean node height.
Results The complete set of partial CO1-and cytochrome b gene sequences, which comprises both those compiled from the literature and from nucleotide databases, and those produced in the present study are presented in Supplementary Table  S2. New CO1 gene sequences have GenBank accession numbers KU497912-KU498038 and KU521523; new cytochrome b gene sequences have GenBank accession numbers KU497752-KU497911 (details in Supplementary Table  S1 ). The ML tree of concatenated (CO1 + cytochrome b) gene nucleotide sequences, rooted by N. trigonoides, showed 9 main statistically supported clades (Fig. 2 ). Here, we distinguished the sister-subclades IVa (N. orientale) vs. IVb (N. varidens) within previous Clade IV  [19, 23]. The 7 other clades were Clades I-III, VII, VIII identified previously  [19, 23] , N.
The ML tree of CO1 gene sequences, rooted by N. trigonoides (Supplementary Fig. S1 ), showed the same 9 haplogroups as those highlighted in the phylogenetic tree of Fig. 2 , plus a tenth lineage represented by the single CO1 gene haplotype from the Ryukyu Islands (GenBank AB485685;  [31] ). All haplogroups had acceptable to strong statistical support, except the haplogroup representing individuals from the Indian Ocean. All 330 individuals characterized by their CO1 gene sequence (except a single individual from India; GenBank HM467799) unambiguously clustered with either one of the 9 lineages of Fig. 2 , or with N. trigonoides. The ML tree of cytochrome b gene sequences, rooted by N. trigonoides (Supplementary Fig. S2 ), similarly showed the same 9 haplogroups as those highlighted in Fig.
previously under N. kuhlii, based on nucleotide sequences of the concatenated CO1+ cytochrome b gene fragments. A total of 133 individual sequences (Supplementary Table  S1 ), aligned over 1640 bp, was retained in the final dataset, after all positions with less than 95% site coverage had been eliminated. N. trigonoides was used as outgroup  [16]. Roman numbers I-VIII designate the haplogroups or clades reported previously  [19]. Numbers at a node are bootstrap scores (from 600 bootstrap resampling runs). Vertical black bars summarize the partition obtained according to Puillandre's gap detection analysis, ABGD. Vertical grey bars summarize the partition into species obtained from GMYC analysis (SPLITS; singlethreshold option). Open bars: partition into species finally retained considering tree topology, nucleotide divergence between lineages, and results of ABGD and GMYC analyses.
area (Fig. 1B ). Similar zones of contact are expected between Clades II and III east of the northern tip of Aceh, between Clades III and N. varidens in the Malacca strait, between N. caeruleopunctata, N. orientale, and Clade II west of the southwestern tip of Java, and between N. australiae and N. caeruleopunctata east of southern Bali (Fig. 1B ). Other contact zones may be possible between N. orientale and Clade VII, between N. australiae and Clade VII, and between Clade VII and Clade VIII (Fig. 1B ). Eighteen Neotrygon spp. individuals (out of 37 tested) were successfully sequenced at the Gh5 intron locus. The sequences have GenBank accession numbers KU497734-KU497751. The ML tree derived from the alignment of sequences, rooted by N. trigonoides, is presented in Fig. 3A.
This may either signal mitochondrial introgression, or reflect incomplete lineage sorting at the Gh5 locus. In addition, at this locus, samples from the Moluccas and West Papua (respectively, our lineages VII and VIII) were distinct from all the other samples, and also from each other. [43] ; Jukes-Cantor model  [51] ) with gamma-distributed rate differences among sites; partial deletion] of Gh5 intron sequences. A total of 18 individual sequences aligned over 356 bp were retained in the final dataset, after all positions with less than 95% site coverage had been eliminated. N. trigonoides was used as outgroup  [16]. Numbers at a node are bootstrap scores (from 1000 bootstrap resampling runs). B. Summary of the Bayesian phylogeny based on partial RAG-1 sequences (redrawn from Fig. 2a  of  [17] ; lineage names edited according to Table  1 ).
) the cytochrome b gene sequence dataset, consisting of 165 blue-spotted maskray and N. trigonoides sequences aligned over a maximum length of 1142 bp; (3) the concatenated CO1 + cytochrome b gene sequence dataset comprising 127 blue-spotted maskray and 6 N. trigonoides sequences; (4) the Gh5 intron sequence dataset, consisting of 18 blue-spotted maskray and N. trigonoides sequences aligned over a maximum length of 359 bp.
Acknowledgments We thank  Jean-Dominique Durand  ( IRD, Ho-Chi Minh Ville ),  Nicolas Hubert  ( IRD, Cibinong ),  Samuel P. Iglesias  ( MNHN, 387 Concarneau ) and  Robert D. Ward  ( CSIRO, Hobart ) for exchanging viewpoints, and five anonymous reviewers for insightful comments on previous versions of this paper. DeAnne Olsen Cravaritis  ( NCBI, Bethesda ) kindly edited the files deposited in GenBank. A. Pavan Kumar  ( ICAR-CIFE, Mumbai ) kindly provided details on specimen VIZNK-01. The fishers, researchers, and travellers who participated in the collection of samples are listed in Appendix A. The background map of the Indo-West Pacific was edited from images downloaded from Digital Vector Maps,  San Diego  (http://digital-vector-maps. com/). Funded by  IRD-UMR 250 ,  NTOU , and  LIPI-P2O.
I 1 , 1 Fig. 1. Sampling sites of blue-spotted maskrays, Neotrygon spp. previously under Neotrygon kuhlii, including new samples from present study, samples from the literature, and additional haplotypes from BOLD, Cryobank and GenBank (details in Supplementary TableS1). Individuals were identified to species according to present revision, from either their COI or cytochrome b gene sequence. Roman numbers I-VIII designate the haplogroups or clades reported previously [19, 23] , four of which have since been described or redescribed [24]  (Table1). Surface of symbol (circle or triangle) proportional to sample size. A. I 1 , I 2 and I 3 : clade I from, respectively, Tanzania (N = 7), Tamil Nadu (N = 7) and Vizakhapatnam (N = 1). V 1 and V 7 : N. australiae from, respectively, Ningaloo Reef (N = 2) and Gulf of Carpentaria (N = 5).
Methods CP1108/NCT01693562 was a nonrandomized phase I/II trial evaluating durvalumab in advanced NSCLC and other solid tumors  [3]. By 29APR2016, 304 previously treated NSCLC patients, median 3 prior lines, received 10 mg/kg of durvalumab q2w ≤12 months. Baseline archived or fresh tumor biopsies were analyzed for PD-L1 (Ventana/SP263) and CD8 (Ventana/ SP239) by IHC. For the marker combination, slides were scored using the product of PD-L1+ and CD8+ cell densities with Definiens' Developer XD 2. 1. 4 software. For PD-L1 alone, ≥25% tumor cells stained for PD-L1 at any intensity were scored positive. Clinical outcomes (ORR, PFS and OS) were analysed based on CD8+ and PD-L1+ densities (n = 163 available) and PD-L1 alone in pre-treatment biopsies using a discovery (n = 84) and validation (n = 79) set.
Results Patients with high pretreatment CD8+ and PD-L1+ densities (prevalence = 36%) had better ORR, OS, and PFS compared to those with low CD8+ and PD-L1+ densities (Fig. 1 ), as well as high PD-L1 expression alone. Conclusions Automated image analysis of CD8+ and PD-L1+ cell densities in baseline tumor biopsies may identify patients with improved outcomes to durvalumab. Trial Registration ClinicalTrials. gov identifier NCT01693562.
Background Natural killer (NK) cells and the innate immune system play a critical role in immunosurveillance, control of tumor growth, and metastasis. NK-cell activation is negatively regulated by inhibitory killer-cell immunoglobulin-like receptors (KIRs); therefore, blocking KIR function may potentiate an anti-tumor immune response and complement other immuno-oncology therapies that enhance T cell activity. We present preliminary efficacy results in patients with squamous cell carcinoma of the head and neck (SCCHN) from a phase I/II study of lirilumab, a fully human monoclonal antibody that blocks inhibitory KIRs on NK cells, in combination with nivolumab, a fully human IgG4 monoclonal antibody that targets the PD-1 receptor, in patients with solid tumors (NCT01714739).
Background The objective of this study is to identify tissue factor (TF) as a novel oncotarget for triple negative breast cancer (TNBC) and BRAF mutated melanoma, both of which are very difficult to treat in clinic, and to develop a novel TF-targeting agent for immunotherapy. To achieve this goal, Hu developed a second generation TF-targeting ICON, named L-ICON, which consists of only the light chain (1-152 aa) of FVII fused to an IgG1Fc. The effects of L-ICON were evaluated as monotherapy or combination therapy with interleukin 15 (IL-15) for the malignancies. Methods TF expression was determined by immunohistochemistry or by flow cytometry. L-ICON protein (GenBank accession no. KY760097) and replication-deficient adenoviral vectors have been developed. Binding activity of L-ICON was determined.
Results At the time of ISA, 27 patients have been enrolled. Patient and disease characteristics are in Fig. 7. At data cut-off on 9/14/2016, 22 patients have completed CRT. Of those patients, 3 required cisplatin dose reductions and 6 required a dose discontinuation. Acute grade (G) ≥ 3 AEs for those completing CRT are in Fig. 8. Median cumulative cisplatin dose is 225 mg/m2. There were no radiation dose-limiting toxicities. Two patients (9%) discontinued pembrolizumab due to irAEs (G2 peripheral motor neuropathy and G3 transaminase elevation). No deaths have occurred.
Methods In order to test whether mIHC can better characterize the tumor immune microenvironment, 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 31 stage II-III melanoma patients diagnosed between 2000 and 2012, with characteristics shown in Fig. 9  for whom pathology from the primary biopsy was shown. Clinical follow up was available on 18 patients of whom 9 patients were alive with no evidence of recurrence, 1 had died of another malignancy, and 7 had died of melanoma. 15 patients had more than 24 months of survival information available but no detailed clinical information. 5 μm slides from either the primary biopsy or subsequent wide local excision procedure were stained using Opal multiplex IHC for DAPI, CD3 (LN10, Leica), CD8  Clinically, Imprime has demonstrated promising efficacy in clinical trials when combined with tumor-targeting or anti-angiogenic antibodies.
Methods The B16F10 experimental metastasis model was used to interrogate Imprime's anti-tumor activity in vivo. B16F10 melanoma cells were injected into the tail vein of syngeneic C57BL/6 mice, seeding the lungs with B16 foci. Outgrowth of these metastatic foci was assessed after treatment with the tumor-targeting anti-tryp1 antibody TA99, Imprime, or the combination. At various times post tumor injection, lungs were examined via multiplexed immunofluorescence (IFC) for markers of immune infiltration and activation. IFC was performed using 7-color staining (Opal technology, PerkinElmer) combined with in situ hybridization (RNA-Scope, ACD). Images were acquired with the Vectra3 multispectral imaging system and cells segmented using Inform (PerkinElmer). Imaging data were transformed into ".
Acknowledgements We thank  Merck  and  Oncosec  for supporting this trial with pembrolizumab and IT-pIL-12, respectfully. Trial Registration ClinicalTrials. govidentifier:  NCT02493361  Acknowledgements Support: Steve and  Cindy Harder ,  Robert W. and  Elsie Franz ,  Wes  and  Nancy Lematta ,  Lynn  and  Jack Loacker , and  The Chiles foundation (BAF). Acknowledgements This work was partly supported by a startup fund from OSUMC, a  Seed Award  from the  OSUCCC TT Program, a Phase 1 L-Pilot Award  from  OSU CCTS  via  NCATS  Award Number  UL1TR001070  and the  Dr. Ralph and Marian Falk Medical Research Trust. IL-15 was obtained from the  NCI Preclinical Repository. Z. H. is the inventor of L-ICON and its uses (US Patent Application #  62/082 , 891 ). Acknowledgements This work was supported by  CURE  Grant  SAP #4100072562  ( Pennsylvania Department of Health ) and  NIH/NCI  5  T32 CA060395  (KMK).
IL-2 was generously provided by  Prometheus Laboratories Inc. Acknowledgements Funding supported by the  Merck Investigator Studies Program. Trial Registration ClinicalTrials. govidentifier:  NCT02586207  Acknowledgements We acknowledge the kind contribution of NHS-muIL12 from  EMD Serono, Billerica, MA. Therapeutic Cancer Vaccines P21 Intracellular trafficking of self-assembled immune signals  Michelle Bookstaver ,  Christopher M Jewell Fischell Department of Bioengineering ,  University of Maryland -College Park, College Park, MD, USA Correspondence :  Michelle Bookstaver  (mlbooks@umd. edu)Journal for ImmunoTherapy of Cancer 2016, 4(Suppl 2): P21  Acknowledgements This work was supported in part by  NSF   CAREER # 1351688  and  Alliance for Cancer Gene Therapy  #  15051543. Acknowledgements 1RO1CA161891 Trial Registration ClinicalTrials.
govidentifier:  NCT01421017 1 INSERM ,  Université Pierre et Marie Curie ,  Université Paris Descartes, Paris , France; 2  Mayo Clinic, Rochester, MN, USA; 3 Earle A. Chiles Research Institute, Providence Cancer Center, Portland, Oregon, USA; 4 Institute of Pathology, University of Bern, Bern, Switzerland; 5 Radboud University Nijmegen Medical Center, Nijmegen, Netherlands; 6 University Erlangen-Nürnberg, Erlangen, Germany; 7 Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada; 8 Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan; 9 Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan; 10 Department of Surgery, Kinki University Faculty of Medicine, Osaka-Sayama, Japan; 11 Division of Clinical Research, Research Center for Innovative Cancer Therapy, Kurume University School of Medicine, Kurume, Japan; 12 First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic ; 13  Sapporo Medical University, Sapporo, Japan ;  14   Institut Roi Albert II, Cliniques universitaires St-Luc ,  Université Catholique de Louvain, Brussels, Belgium ;  15  The  Gujarat Cancer & Research Institute, Ahmedabad, India; 16 Institute for Cancer Research, Xi'an Jiaotong University, Xi 'an, China; 17  Karolinska Institutet , Karolinska University, Stockholm, Sweden; 18 Humanitas Clinical and Research Center, Rozzano, Italy; 19  Istituto Nazionale Tumori Fondazione Pascale , Naples, Italy; 20  Sidra Medical and Research Center, Doha ,  Qatar Correspondence: Bernard A Fox  (bernard.
These included increases ary study objectives include characterization of the safety, of AF. These were grade 2 events by CTCAE 4. 0 criteria and managed Trial Registration in GZMM, PDCD1, CD8B, CD8A, and CTLA4 and decreases in IL18, pharmacokinetics, pharmacodynamics, and preliminary antitumor ac- with appropriate medication without further sequelae. ClinicalTrials. gov identifier NCT01976585. IRAK3, and TXNRD1. tivity of MGD009. All tumor evaluations will be carried out by both Conclusions Conclusions Response Evaluation Criteria in Solid Tumors (RECIST 1. 1) and im- α-TEA treatment resulted in stable disease in 80% of patients lasting This hypothesis-generating microarray analysis identified genes up-mune-related RECIST. between 1 and 22+ months. AF was observed commonly in patients P11 regulated in circulating peripheral blood cells after T-VEC monother-Trial Registration Trial Registration with a medical history of AF, and was managed with appropriate Preliminary safety and efficacy data for radiotherapy and PD-L1 apy and combination treatment.
We plan to further evaluate these ClinicalTrials. gov identifier NCT02628535. ClinicalTrials. gov identifier NCT01288963. medication. No clinically meaningful grade 3 or 4 toxicities were ob-checkpoint blockade in metastatic non-small cell lung cancer: is genes and other potential pharmacodynamic markers in phase II. timing everything? served. Plasma α-TEA levels increased proportionally without any in-Arta Monjazeb 1 , Megan E Daly 2 , Jonathan Riess 2 , Tianhong Li 2 , William J dication that steady state levels were achieved. α-TEA may function through enhancing pre-existing CD8+ T cell-mediated anti-tumor Murphy 1 , Karen Kelly 2 Trial Registration ClinicalTrials. gov identifier NCT01740297. activity. P9 Phase I, first-in-human, open label, dose escalation study of MGD009, a humanized B7-H3 x CD3 dual-affinity re-targeting (DART®) protein in patients with B7-H3-expressing neoplasms or B7-H3 expressing tumor vasculature Anthony W Tolcher 1 , Evan W Alley 2 , Gurunadh Chichili 3 , Jan E Baughman 4 , Paul Moore 3 , Ezio Bonvini 3 , Syd Johnson 3 , Sadhna Shankar 3 , James Vasselli 3 , Jon Wigginton 3 , John Powderly 5 1 START -South Texas Accelerated Research Therapeutics, LLC, San Antonio, TX, USA; 2 Penn Presbyterian Medical Center, University of Pennsylvania, Philadelphia, PA, USA; 3 MacroGenics, Inc.