dataesr/scientific-paragraphs-categorization huggingface dataset:
Clofarabine Clofarabine is a purine nucleoside metabolic inhibitor  [61]  that is structurally related to cladribine  [62]. It is approved in the USA and European Union for treatment of pediatric patients 1-21 years old with R/R acute lymphoblastic leukemia after at least two prior regimens  [61, 63]. Clofarabine inhibits DNA polymerases and ribonucleoside reductase; it also causes disruption of mitochondrial membrane integrity with release of cytochrome C and other apoptosisinducing factors, leading to programmed cell death  [61, 63]. A phase 1/2 study of the nucleoside analogue clofarabine in patients with R/R T-cell or natural killer (NK) cell lymphoma, including R/R ATL (NCT00416351), is ongoing.
Pralatrexate Pralatrexate is a folate analogue metabolic inhibitor. It is currently approved in the USA for the treatment of patients with R/R PTCL  [64]. Pralatrexate competitively inhibits dihydrofolate reductase and is a competitive inhibitor for polyglutamylation by the enzyme folylpolyglutamyl synthetase. This inhibition results in the depletion of thymidine and other biologic molecules  [64]. The PROPEL study was a phase 2 study of pralatrexate in patients with R/R PTCL (however, the study population included only one patient with ATL)  [65]. A phase 1/2a study evaluating pralatrexate plus the histone deacetylase (HDAC) inhibitor romidepsin in R/R lymphoid malignancies (including ATL) or multiple myeloma is currently recruiting (NCT01947140) (see Table  1 ).
Mogamulizumab   also has been shown to deplete T reg cells, resulting in increased antitumor immune response  [72, 73] , thereby demonstrating activity as an immune-oncology agent. A recent translational study in patients with advanced or recurrent CCR4-negative solid cancers demonstrated that mogamulizumab depleted FoxP3? CD4 T reg cells and that the effect was generally durable for more than 6 months after finishing eight infusions of mogamulizumab  [74]. The depletion of T reg cells may explain why mogamulizumab use in the pre-transplantation setting has been associated with an increased risk of severe graft-versus-host disease (GVHD) and GVHD-related mortality  [75, 76]. Infectious (n = 2) Carfilzomib NCT01336920 (USA) 1 15 R/R T- Completed clinical trials of mogamulizumab in ATL include a phase 1 trial in relapsed ATL/ PTCL  [46]  and a phase 2 trial in relapsed ATL  [47].
Following binding of the ADC to CD30-expressing cells and internalization of the ADC-CD30 complex, MMAE is released by proteolytic cleavage, resulting in targeted cell death via the microtubule-disrupting actions of MMAE  [77] [78] [79]. Clinical trials include two ongoing trials in patients with R/R CD30? lymphomas, including some ATL patients (a pilot study in patients with R/R disease [NCT01703949] and a phase 2 study in R/R CD30-low mature T-cell lymphomas [NCT01805037]) (see Table  1 ).
Alisertib Alisertib is an investigational Aurora A kinase (AAK) inhibitor. Alisertib causes G2/M arrest, abnormal mitotic spindle formation, the appearance of tetraploidy, and subsequent apoptosis  [52]. A completed phase 2 clinical trial evaluated alisertib in patients with R/R PTCL (that included four patients with R/R ATL)  [52]. A phase 1 trial of alisertib plus the HDAC inhibitor vorinostat in patients with R/R Hodgkin lymphoma, B-cell NHL, or PTCL (including ATL; NCT01567709) is ongoing (see Table  1 ).
Others Agents with Clinical Trial Results in Patients with R/R ATL Arsenic trioxide has been evaluated in combination with IFN in patients with R/R ATL (results summarized in Table  1 )  [45]  and demonstrated efficacy in combination with AZT and IFN in patients with newly diagnosed chronic ATL  [87, 88]. In lymphoma, the combination of IFN/AZT/arsenic increased the time to progression (Hermine et al. , unpublished data). The anti-CD25 recombinant immunotoxin LMB-2 in combination with fludarabine and cyclophosphamide was evaluated in a phase 2 study in patients with CD25? ATL, the majority of whom were previously treated (see Table  1 )  [58]. Agents with Completed (But Unpublished) or Ongoing Studies in R/R ATL A phase 1 study of the proteasome inhibitor carfilzomib in patients with R/R T-cell lymphoma, including R/R ATL (NCT01336920) is ongoing (not recruiting).
A phase 2 study of the immune toxin IMTOX-25 in patients with R/R CD25? ATL (NCT01378871) has been completed; results have not yet been published. Two studies of the JAK inhibitor ruxolitinib are currently recruiting: a phase 2 study in patients with smoldering or chronic ATL [or previously treated lymphomatous or acute ATL with clinically indolent behavior indicated by lack of significant symptoms and treatment-free interval of greater than 6 months (NCT01712659)] and a phase 2 study in patients with R/R diffuse large B-cell or peripheral T-cell NHL, including ATL (NCT01431209). Studies of HDAC inhibitors include a phase 2 study of panobinostat in patients with R/R NHL (including recurrent ATL) that is currently ongoing (NCT01261247) and a phase 2 study of HBI-8000 in patients with R/R ATL that is currently recruiting (NCT02955589).
A study of the PD-1 antibody pembrolizumab in R/R peripheral T-cell NHL (including ATL) is currently recruiting (NCT02535247). A phase 1 study of the dual PI3 K delta/gamma inhibitor RP6530 in patients with R/R peripheral (or cutaneous) T-cell lymphomas is currently recruiting (NCT02567656). See Table  1  for additional information on these studies.
Selected Agents with Studies in ATL and Related Conditions Additional studies of HDAC inhibitors and checkpoint inhibitors in patients with ATL (not specifically R/R ATL) and other T-cell malignancies are also of interest. The HDAC inhibitors romidepsin and vorinostat have demonstrated efficacy in and are FDA approved for treatment of R/R cutaneous T-cell lymphoma  [89] [90] [91] [92]. Studies of HDAC inhibitors (in combination with AZT and/or IFN) in patients with ATL include a recently completed phase 1/ 2 trial that evaluated valproic acid in combination with AZT/IFN as maintenance therapy (NCT00854581)  [93]  and an ongoing study of belinostat in combination with AZT as consolidation therapy (NCT02737046)  [94]. Clinical trials of checkpoint inhibitors include a phase 2 study of the PD-1 antibody nivolumab in patients with ATL (NCT02631746).
ACKNOWLEDGEMENTS Funding. Funding to support the preparation of this manuscript, article processing charges, and open access fee was provided by  Kyowa Kirin International (Bedminster, NJ, USA) , a subsidiary of  Kyowa Hakko Kirin Co. Ltd. Medical Writing, Editorial , and  Other Assistance. The authors thank  Sherri D. Jones  of  MedVal Scientific Information Services, LLC  for medical writing and editorial assistance, for which funding was provided to MedVal by  Kyowa Kirin International , a subsidiary of  Kyowa Hakko Kirin Co. Ltd. This manuscript was prepared according to the  International Society for Medical Publication Professionals' ''Good Publication Practice  for Communicating Company-Sponsored Medical Research: The  GPP3 Guidelines. ''.
Introduction The identification of species is central in ecology, conservation biology, systematics, and related disciplines (species inventories and community studies, ecosystem management, establishment and improvement of environmental public policies, taxonomic reviews, and management of natural history collections)  (Oliver 1988 , Hebert et al. 2003 , Smith et al. 2008 , Vander Zanden et al. 2010). Europe is one of the best-known parts in the world in terms of biodiversity  (Fontaine et al. 2012) , especially concerning distribution patterns at the country scale. This has been highlighted by the release of the Fauna Europaea database since  2004 (de Jong et al. 2014)) , which gathers the scientific names and distributions of all living European animal species and is assembled by a large network of specialists.
Interactive identification key construction and statistics Digitalization of the 47 species was performed using Xper 2 v. 2. 3. 2  (Ung et al. 2010 ) and transferred to Xper 3 (Vignes-  Lebbe et al. 2016). These softwares are dedicated to manage structured taxonomic descriptions, to analyse these descriptions and to produce keys  (Kerner et al. 2011 , Corvez and Grand 2014 , Martin et al. 2015). A wiki and a documentation of Xper 3 are available at http://wiki. xper3. fr/index. php/ UserManualXper3. An Xper knowledge base is a set of items described using the same model and terminology, and documented by texts and images. In this key there are 66 items covering 47 species and 19 intraspecies colour forms. The descriptive model consists of a hierarchy of descriptors and a chosen terminology for expressing different possible values (states).
For a given descriptor the sum of the comparison for all pairs of items is a measure of its ability to distinct taxa (discriminatory power). The discriminatory power, which represents the quantitative assessments of the ability of a descriptor to distinguish taxa, is measured with the Xper original index  (Lebbe 1991 ) implemented in the Xper 2 software. This index is based on the incompatibility between descriptions. Two taxa are incompatible (or dissimilar or discriminated) if for one given descriptor there are no states of descriptors in common. For each descriptor the index value ranges between 0 (null discriminatory power of the descriptor) and 1 (the descriptor can distinguish all taxa). Comparisons within and between genera are made with the "compare groups" and "compare items" options of Xper 3.
However these keys are single access, e. g. , MobileKey  (Weber and Hagedorn 2010)  or the iRecord Ladybirds mobile application, and do not support all the possibilities provided by the free-access keys. Recently, a set of software and applications for transferring the information present in a local Xper database to an Android application has been developed  (Troudet 2012). For example, the Malaco-fr application provides an interactive way to identify French snails in the field and without internet connection  (Gargominy and Ripken 2011). The free-access key of French ladybirds described in this study will soon be transferred to such a mobile application,.
Acknowledgements We thank  Clémentine Dantard  for the illustrations, and  Frédéric Chevaillot ,  Fabrice Duvivier ,  Jean-François Godeau ,  David Gonzales ,  Donald Hobern ,  Guillaume Jacquemin ,  Julien Aït El Mekki ,  Andgelo Mombert , and  Gilles San Martin  for providing field pictures of the species. We also thank  Sylvain Bouquin  for his technical help with the Xper system, and  Estelle Bourdon  and  Donald Davesne  for proofreading.
r-project. org) based on the correlation coefficient r 2 between polymorphic informative sites and the distance in base pairs (bp) between sites. Locus-by-locus estimates of net divergence between taxa  (Nei 1987) , and the number of shared, exclusive and fixed polymorphic sites and haplotypes for each locus were determined using SITES 1. 1  (Hey and Wakeley 1997). Sequences from P. taeda were obtained from GenBank for outgroup comparisons. The number of haplotypes (N) and haplotype diversity (H d ) were computed for each gene using DnaSP v5  (Librado and Rozas 2009). The number and frequency of unique and shared haplotypes (the entire length of the sequenced gene fragments) in pairwise comparisons between taxa was calculated with Arlequin v. 3. 5  (Excoffier and Lischer 2010).
Population structure and differentiation Genetic distance based on all polymorphic mtDNA sites was calculated and used in principal coordinate analysis (PCoA) to show genetic relationships between populations and taxa. Genetic relationships between samples at nuclear loci were explored using BAPS 6. 0  (Corander and Tang 2007)  and STRUCTURE 2. 2  (Pritchard et al. 2000) , for values of K from 1 to 15 with estimates averaged over ten independent runs in each case, with optimal K determined from likelihood and assignment proportions. For BAPS 6. 0, datasets comprising all samples were tested. The Codon linkage model was selected, with 100 iterations to estimate admixture coefficients, 100 reference individuals and 10 iterations to estimate admixture coefficients for the reference individuals.
For STRUCTURE 2. 2, datasets including all polymorphic sites, and excluding linked sites as determined by a significant Fisher's exact test after Bonferroni correction, were tested. The correlated allele frequencies model was used; burn-in was set to 100,000 and run length to 1,000,000. To further assess among-population differentiation, we used principal coordinate analysis (PCoA) based on the mean net distance between populations across all SNPs, estimated with the Jukes-Cantor nucleotide substitution model with pairwise deletion. The hierarchical distribution of multilocus genetic variation among taxa, regional groups and populations was estimated using an analysis of molecular variance (AMOVA) with Arlequin v. 3. 5  (Excoffier and Lischer 2010).
Signatures of selection and divergence First, genetic differentiation in pairwise comparisons within and between taxa was studied locus-by-locus at both haplotype and SNP/indel level. Significance was estimated by 1000 permutations of the samples between populations, regional groups and taxa using Arlequin v. 3. 5. The false discovery rate (FDR) adjustment for multiple testing was conducted using the q value package in R  (Bass et al. 2015 ) (lambda = 0. 15, FDR level = 0. 01). The estimates of the overall proportion of true null hypotheses (pi0) and the q values (that reflect the expected proportion of false positives among significant results) were calculated based on the distribution of p values for the set of tests conducted  (Storey and Tibshirani 2003). Among-group and among-population diversity was estimated by the nearest neighbour statistic, S nn  (Lynch Crease 1990) , and tested for significance using 1000 permutations, where samples were randomly assigned to groups.
Second, the full SNP dataset was used to test for outlier loci among populations using Bayesian hierarchical analysis  (Foll and Gaggiotti 2008). In the first approach, coalescent simulations were used to estimate a null distribution and confidence intervals around the observed values, which allowed for the identification of outliers by locusspecific F ST conditioned on the multilocus distribution of F ST values. Outliers that were highly differentiated relative to background variation may indicate a locus under directional selection. Each simulated group consisted of 100 subpopulations, and 20,000 replicates of the coalescent were used to identify the expected distribution of F ST. The significance thresholds of the F ST values were set at 95% and 99% from the simulated data using Arlequin v.
4 to 35. 5%  (Strasburg et al. 2012). For instance, 3. 4% of outliers for divergence were found in Helianthus annuus and H. debilis  (Ahrens et al. 2018; Scascitelli et al. 2010) , 5-28% in Quercus robur and Q. petraea  (Guichoux et al. 2013 ) and about 30% in hybrid zones of Populus alba and P. tremula  (Lexer et al. 2010). In our dataset, the majority of loci that showed both evidence of selection in compound neutrality tests and an outlier pattern of differentiation at the within-taxon level also showed evidence of significant between-taxon divergence. Therefore, in part, selection has operated on both evolutionary and more recent, ecological timescales. However, not all genes that showed significant patterns of between-taxa divergence also showed evidence of selection within taxa and vice versa.
Materials and Methods The studied material was received on loan from CAY and includes six fertile specimens (two with flowers and four with fruits) and three sterile specimens of the new species, plus three fertile specimens of V. parviflora (the species morphologically most similar). A comprehensive bibliographic survey of publications describing Vantanea species  (Cuatrecasas 1961; Rodrigues 1982; Sabatier 1987; McPherson 1988; Gentry 1990; Sabatier 2002; Herrera et al. 2010)  was carried out. Digitized herbarium sheets of all Vantanea species were downloaded from various database portals, including the New York Botanical Garden (http://sweetgum. nybg. org/science/vh/), the Muséum national d'Histoire naturelle (https://science. mnhn. fr/institution/mnhn/collection/p/item/search/form?lang=en_US), the Smithsonian National Museum of Natural History (http://collections.
nmnh. si. edu/search/botany/) and the Kew Royal Botanic Gardens (http://apps. kew. org/herbcat/gotoSearchPage. do). Terminology of leaf and inflorescence are based on  Harris & Harris (2001). The conservation status was evaluated using the IUCN Red List criteria (IUCN 2012); the Area of Occupancy (AOO) was calculated by using the online "GeoCAT" software "http://geocat. kew. org" (Bachman et al. 2011). Diagnosis:-Vantanea maculicarpa is distinguished from all other species of Vantanea by its fruits that are covered by white lenticels, a character so far unknown in this genus as all other species of Vantanea have smooth, slightly pubescent or rarely tuberculous fruit surface (V. tuberculate  Ducke (1938: 31, pl. 5 )). Fruits shape is globose, another distinctive feature of V. maculicarpa, as fruits are mostly ovoid or ellipsoid in this genus.
Mass spectrometer ionization voltage was 70 eV, mass scan range: 40-350 mass units and ion source temperature was 200 o C. Identification of EO chemical composition was based on comparison of compound mass spectra with databases (Wiley 7 library -Wiley, New York, NY, USA; Adams 2007) and comparison of their retention indices (relative to series of n-alkanes C9-C40) with internal database retention indices and literature retention indices using NIST2002 (National Institute of Standards and Technology, Gaithersburg, MD, USA). [28, 29] he internal database of compounds was created during previous analyses from authentic compounds obtained commercially and from more than thousand EO obtained during our previous studies. The percentages of components were calculated as mean values from the GC and GC-MS peak areas.
Acknowledgment. We would like to thank  Spencer C. Brown  for his assistance in cytometry at the  Imagerie-Gif, Plateforme de Cytométrie CNRS-I2BC, Gif-sur-Yvette, France. This work was funded in part by  Croatian Science Foundation  under the project  IP-2014-09-6897. This work was partially result of the project " Chemical and biological observation of selected plant species of Croatia " financially supported by the  Ambassade de France en Croatie ,  Service de Cooperation et d'Action Culturelle; Agency for Mobility and EU Programmes ,  Centre National de la Recherche Scientifique de France (CNRS)  and  Croatian Ministry of Science, Education and Sport.
Excessive negative energy balance (EB) has been associated with decreased reproductive performance and increased risk of lameness and metabolic diseases. On-farm, automated EB estimates for individual cows would enable dairy farmers to detect excessive negative EB early and act to minimize its extent and duration by altering feeding. Previously, we have shown that EB can be estimated from frequent measurements of body weight (BW) and body condition score (BCS) changes, referred to as EB body. In this study, we investigated the robustness and sensitivity of the EB body method to assess its genericity and on-farm applicability. We used 5 data sets with BW of lactating cows (name of data set in parenthesis): 65 Holstein cows in a French feeding trial (INRA); 6 Holstein cows in a British feeding trial (Friggens); 31 Holstein cows and 17 Jersey cows in a Danish feeding trial (DCRC); 140 Holstein cows in a British feeding trial (Scotland's Rural College, SRUC); and 1,592 Holstein cows on 9 Danish farms with milking robots (automatic milking system).
We used the INRA and Friggens data sets to develop a dynamic formula to correct BW for increasing residual gut-fill (RGF) during early lactation. With the DCRC data, we tested the effect of smoothing parameters and weighing frequency on EB body. Also, 2 robustness tests were performed using the SRUC data to test the effect of diet change on BW and the automatic milking system data to test the effect of farm on BW variation. Finally, we combined the results into a blueprint describing different ways to calculate EB body depending on the purpose and on the availability of BCS. The dynamic RGF adjustment resulted in a lower empty BW during early lactation than that obtained with the previously used constant RGF. The double-exponential smoothing method used to correct for meal-related gut-fill was robust to choice of smoothing parameters.
Thus, provided that we know how intake changes, we can adjust RGF accordingly. For this purpose, we made use of data from 65 Holstein Friesian cows housed indoors from August 2014 to June 2015 at the INRA PEGASE experimental farm (INRA, Le Rheu, France), referred to as the INRA data. Across lactation (1 to 240 DIM), these cows weighed on average (SD in parentheses) 620 (70. 2) kg, range 482 to 776 kg; their mean DMI was 21. 3 (2. 65) kg/d, range 16. 6 to 27. 0 kg/d, and their mean milk yield (MY) was 30. 5 (4. 87) kg/d, range 21. 7 to 43. 4 kg/d. The cows were fed ad libitum using the same TMR (65% maize silage and 35% concentrate) throughout lactation. Feed was distributed twice per day after milking. Dry matter intake was measured daily and individually as the difference between offered and next day's refusal weight in each individual feed trough.
Mean DMI per day of the INRA cows was calculated. These daily mean DMI reached a plateau level that was maintained between 100 and 200 DIM. The average intake in this period was used as a reference level of intake, and the proportionate intake was calculated for each DIM by dividing daily mean DMI by the average DMI level from 100 to 200 DIM. An exponential model was fitted to describe the change in proportionate intake with time (Equation  1 ): proportionate intake (kg/kg) = a × (1 -e -b × DIM ) + c. [1] In this equation, a + c is the asymptote (approximately = 1), c is the starting level, and coefficient b describes the curvature of the exponential. This time-dependent equation provides the basis to substitute our previously fixed value of RGF with a dynamic RGF equation. To check the genericity of this equation, we used an older and second data set of 6 Holstein Friesian cows housed at the Scotland's Rural College (SRUC) Dairy Research Center (Dumfries, UK), which were fed the same TMR (grass silage and 100 g of concentrate per kg of fresh weight, designed to limit the intake) from 11 to 231 DIM.
These cows constituted the control group fed low-concentrate TMR in the trial described in detail by  Friggens et al. (1998) , hereafter referred to as the Friggens data. We compared the 2 RGF correction methods by calculating the difference between EBW corrected with constant RGF and EBW corrected with dynamic RGF derived from Equation [1] using the Danish feeding trial (DCRC) data. Meal-Related Gut-Fill Variation. The analysis of meal-related gut-fill variation was performed on data from 17 Danish Jersey and 31 Danish Holstein cows of mixed parity. The cows were housed throughout the year and milked in an automatic milking system (AMS) at the Danish Cattle Research Centre (Tjele, Denmark). The cows were weighed automatically at each milking (i. e. , approximately 2. 5 times/d). They calved between October 2005 and May 2006.
Across lactation (2 to 305 DIM), the Holstein cows weighed on average 565 (54) kg, range 479 to 721 kg, and their mean MY was 27. 0 (4. 79) kg/d, range 15. 1 to 36. 9. The Jersey cow mean BW was 444 (50. 8) kg, range 368 to 543 kg, and their mean MY was 17. 5 (2. 72) kg/d, range 12. 7 to 22. 2 kg/d. Cows and housing were described in more detail in  Thorup et al. (2013) ; feed composition was described by  Weisbjerg and Munksgaard (2008). This data set is hereafter referred to as DCRC data. The BCS was assessed once every 2 wk, and BCS was smoothed across lactation using a natural cubic spline of degree 3 as described in  Thorup et al. (2012). In our first study, we adjusted BW for meal-related gut-fill variation by smoothing BW by QR using the 20% lower quantile, which is not the same as assuming 20% gut-fill  (Thorup et al.