dataesr/scientific-paragraphs-categorization huggingface dataset:
Associations were also observed between the likelihood of FICHCOMP drug prescription and age, gender and the presence of comorbidities. The lower likelihood of prescription in older patients and in patients with those comorbidities taken into account in treatment decisions (MCT meetings) may be explained by reticence to use these treatments in patients who are already frail. For some of these medications, the prescribing indication lists certain comorbidities and the elderly in the precautions for use or contra-indications of the medication. The reason why prescription rates are lower in men than in women is unclear. We have previously shown using the PMSI database that survival is better in women with incident metastatic lung cancer than in men  [14] , which may indicate that their treatment or disease trajectories are different to those of men.
This study was performed using data from the PMSI database, which is an exhaustive data on all patients hospitalised in France. Since diagnosis and management of cancer patients is exclusively hospital-based in France, it should be possible to identify all incident cases of lung cancer in this database at a national level. Indeed, the number of such cases of that we identified (41715) is close to the number of incident cases in France for 2012 documented by the National Cancer Institute (~40,000)  [15]. The contemporary quality of coding in the PMSI database is considered to be high and a recent comparison of standardised incidence ratios for different types of cancer determined from the PMSI and from local cancer registries has shown that the two sources provide very similar estimates  [16].
The North American studies have suggested that patients living in rural areas or far from hospitals have a lower access to treatment  [24] [25] [26] , a difference which was not observed in our study or in the British studies  [17]. This difference probably reflects the much lower population density, and in consequence density of hospitals, in rural areas in North America compared to Europe. The absence of influence of rurality in access to innovative drug is also an important finding. The present study cannot address whether the differences in access to FICHCOMP medications as a function of social deprivation has a relevant clinical impact. Nonetheless, in a previous analysis of the PMSI database  [14] , it was found that social deprivation was also associated with reduced survival following diagnosis both at the metastatic and non-metastatic stages.
The strengths of the present study include the population-based approach, with a cohort of all lung cancer patients managed in France in 1 year with two-years of follow-up. Nonetheless, the use of this data source presents certain drawbacks. Firstly, at the patient level, demographic variables were limited to gender and age. No information is available in the PMSI database on smoking status, tumour histology and staging, or functional performance. Histology is a major criterion for systemic treatment strategy and several FICHCOMP drugs are actually specific to non-squamous NSCLC. This is the case for the two most-widely used drugs in Patients could be prescribed more than one extra-DRG drug, so these frequency counts are not mutually exclusive a These drugs were withdrawn from the special funding list (liste en sus) during the data collection period our study (pemetrexed and bevasizumab).
The observed association between access to these drugs and social deprivation may thus be even larger if only non-squamous NSCLC had been considered. Secondly, socioeconomic variables could only be estimated at the level of the municipality of residence of the patient, which is only a proxy marker of individual socioeconomic status. Thirdly, it is also important to note that private hospitals, which account for one-fifth of lung cancer diagnoses in France did not enter data on the use of expensive drugs to the FICHCOMP database at the time of the study. For this reason, it is possible that the extent of use of these drugs and the determinants of use, may differ between the private and public sectors. Finally, it was also not possible to extent the analysis to access to oral tyrosine kinase inhibitors, since these are delivered in community medicine and are thus not available in the FICHCOMP database.
At the time of this analysis only medications targeting EGFR were available. Molecular testing is carried out systematically on all patients with lung cancer in France  [30]  and EGFR mutations and ALK rearrangements are observed in around 16% of patients  [31]. The proportion of patients with metastatic lung cancer who are eligible for treatment by tyrosine kinase inhibitors targeting EGFR is relatively low. It should also be noted that treatment paradigms for metastatic lung cancer are rapidly evolving with the introduction of immunotherapies, the first of which was licensed in France in February 2016, now included in the FICHCOMP list. This development may have consequences for the pattern of use and access to FICH-COMP drugs for the treatment of metastatic lung cancer. The data collected in the present study will serve as a useful reference point to assess such changes in future studies.
Availability of data and materials The analysis described in this manuscript was performed in a national database (Programme de Médicalisation des Systèmes d'Information; PMSI) belonging to a third-party, namely the French Ministry of Health. Access to this database is freely available to researchers on reasonable demand, upon request to the relevant agency, the Agence technique de l'information sur l'hospitalisation, 117 boulevard Marius Vivier Merle, 69,329 Lyon CEDEX 03, on condition that the analyses envisaged have been authorised by the French Data Protection Agency (Commission nationale de l'Informatique et des Libertés, 3 Place de Fontenoy, 75,007 Paris).
We found similar features in published datasets using two other viruses: Ebola virus (EBOV; -ssRNA genome) and a herpesvirus (dsDNA genome), both produced with the Illumina Nextera protocol. These canonical features suggest that artificial chimeras are generated by intra-molecular template switching of the DNA polymerase during the PCR step of the Nextera protocol. Finally, a published Illumina dataset using the Flock House virus (FHV; +ssRNA genome) generated with a protocol preventing artificial recombination revealed the presence of 1-10 bp microhomology motifs in FHV-FHV chimeras, but very few recombining fragments were in opposite orientations. Our analysis uncovered sequence features characterizing recombination breakpoints in short-read sequencing datasets, which can be helpful to evaluate the presence and extent of artificial recombination.
, 2013; Edgar et al. , 2011; Görzer et al. , 2010; Haas et al. , 2011; Routh et al. , 2015; Shao et al. , 2013; Zanini et al. , 2017). In this study, we were not able to observe any convincing evidence of biological recombination between DENV and mosquito RNA, suggesting that it is unlikely to be frequent. However, using appropriate controls, we investigated the nature of artificial chimeras detected in our sequencing libraries. To generalize our findings, we also analyzed multiple published sequence datasets generated with similar sequencing protocols. Together, our results uncover sequence features typical of artificial chimeras, which may help detect and characterize such artifacts in future studies.
Detection of chimeric reads Detection of chimeric reads resulting from either host-virus or virus-virus recombination used an approach previously developed to search for moth sequences integrated into genomes of the AcMNPV baculovirus  (Gilbert et al. , 2016). Briefly, this approach involves blastn  (Camacho et al. , 2009)  homology searches of the sequencing reads against reference genomes and/or transcriptomes. Searches were performed separately with the DENV genome (Genbank accession number: HG316481), with the Ae. albopictus genome (MNAF02000000) and with the Ar. vulgare genome (LYUU01000000), allowing for the recovery of two possible hits per read in each blast (option -max_target_seqs 2). The following steps were performed with custom R (R Core Team 2017) scripts. All reads containing a region of at least 20 bp that aligns multiple times to one or more reference genomes were identified.
(2016). Reanalysis of the datasets published by  Routh et al. (2015)  (see below) yielded chimeric read counts similar to those obtained by these authors despite the use of different methods. Importantly, the approach designed by  Routh and Johnson (2014)  and  Routh et al. (2015)  does not allow the identification of overlapping alignments in the chimeric reads. It first uses a read mapper [Bowtie2  (Langmead and Salzberg 2012) ] to find the best alignment between a chimeric read and a reference genome, cuts the remaining unaligned portion of the chimeric read and searches for the best alignment between this second read portion and the same or another reference genome. Hence, the second alignment cannot include a portion of the read involved in the alignment of the first read portion, thereby precluding recovery of possible overlaps between alignments of the two read portions.
Ribosomal 18S RNA chimeras were identified by blasting all reads on an 18S rRNA sequence of Ar. vulgare (Genbank accession number: AJ287061. 1). The presence and properties of chimeras found in other datasets was examined in a published high-throughput sequencing dataset of EBOV produced with the same library preparation protocol as in the present study  (Gire et al. , 2014). Unlike DENV, EBOV (Mononegavirales, Filoviridae) is a -ssRNA virus. To detect EBOV-EBOV chimeras, all reads were aligned to the Makona-G3686 EBOV genome (accession number: KM034562) with blastn, followed by the same analysis of blast results described above. Whether chimeras could be formed during the synthesis of cDNA or during the PCR step of the Nextera library-preparation protocol was assessed by analyzing in the same fashion a published Illumina dataset produced to sequence the genome of a DNA virus, the Macropodid herpesvirus 1 (MaHV-1)  (Vaz et al.
, 2016). Finally, a high-throughput sequencing dataset of FHV published by  Routh et al. (2015) , which is devoid of artificial chimeras, was reanalyzed. This dataset allowed the characterization of properties of biological recombination events in an RNA virus, in particular the microhomology length between recombining sequences, using the same protocol applied to the other datasets. In their study,  Routh et al. (2015)  used click chemistry rather than enzymatic reactions for the ligation of Illumina adaptors. The method generates unbiased libraries, with an extremely low artificial recombination rate. FHV is a +ssRNA virus belonging to the Alphanodavirus genus in the Nodaviridae family. It encapsidates a bipartite genome, composed of RNA1 (3,107 bp), which encodes the viral RdRp, and RNA2 (1,400 bp), which encodes the viral capsid protein.
The observed proportion of pillbug-DENV chimeric reads involving pillbug ribosomal RNA (73%) was not significantly different from the proportion of all pillbug reads assigned to rRNA (Chi 2 p-value = 0. 4; 1 df). This indicates that the probability for pillbug sequences to recombine in vitro with DENV sequences mainly depends on their relative proportions in the RNA extracts. The proportion of pillbug and mosquito reads aligning to rRNA genes (74% and 77%, respectively) is consistent with previous RNAseq datasets produced without rRNA depletion  (O'Neil et al. , 2013). We detected 566 mosquito-DENV chimeric reads, representing 555 unique chimeras. None of the recombination breakpoints we sequenced were found to involve a mosquito TE. Instead, most of the chimeras (74%) contain mosquito rRNA, a proportion that is not significantly different from that observed among all mosquito reads (Chi 2 p-value = 0.
4; 1 df). It is noteworthy that the number of mosquito-DENV chimeras is lower than expected given the number of pillbug-DENV chimeras and the proportion of reads from each species in the whole dataset (Chi 2 p-value , 0. 001; 1 df). The reason underlying this discrepancy is unclear and we could not find any evidence suggesting it may be biological. On the opposite, the lower proportion and similar distribution of microhomology length of mosquito-DENV chimeras compared to artificial pillbug-DENV chimeras (Figure  1 ), indicate that most, if not all, mosquito-DENV chimeras were artificially produced. Interestingly, the majority of the pillbug-DENV and mosquito-DENV junctions (56% and 57%, respectively) are characterized by the presence of 1-20 bp microhomologies (Figure  1 ). The distributions of microhomology lengths for both types of chimeras are very similar to each other and at the same time clearly higher than those expected by chance.
Canonical features of chimeras found in various Illumina Nextera sequencing datasets DENV-DENV chimeric reads were far more numerous than arthropod-DENV ones (Table  1 ), which can be explained by the high proportion (70%) of DENV reads in the datasets. DENV-DENV breakpoints are also characterized by the presence of 1-20 bp micro-homologies and the microhomology length distribution clearly differs from that expected by chance (Figure  2A ). Most DENV-DENV recombination events involved sequences separated by distances that are much shorter than expected if recombination took place randomly along the DENV genome (Figure  2B ). Plotting the density of recombination breakpoints along the DENV genome (Figure  2C ) did not reveal any particular hotspots, indicating that recombination takes place along the entire length of the DENV genome at similar frequencies.
Interestingly, the vast majority of DENV-DENV chimeras (60,781 out of 81,516, $74. 5%) involve sequences in opposite orientation. We detected 8,170 unique intra-pillbug ribosomal RNA breakpoints that are characterized by the same features as DENV-DENV breakpoints, i. e. , most of them (81%) show 1-20 bp microhomology as well as evidence of non-templated nucleotide addition and breakpoints devoid of microhomology (Supplementary Figure  1 ), recombination between fragments in opposite orientation (84. 4% of the chimeras) that are typically distant by a few dozen nucleotides. By analyzing the EBOV dataset of  (Gire et al. , 2014) , we found 144,556 chimeric reads representing 16,504 different EBOV-EBOV breakpoints, which were characterized by the same features as DENV-DENV or pillbug-pillbug chimeras (Supplementary Figure  2 ).
The length of microhomology between recombining sequences was longer than expected by chance, most recombining sequences were distant from less than 100bp and were in opposite orientations (65% and 92%, respectively). Finally, our analysis of the herpesvirus dataset of Vaz et al. (2016) detected 2,507 MaHV-1-MaHV-1 chimeric reads representing 1,139 different breakpoints. These were characterized by features similar to those of RNA breakpoints (Supplementary Figure  3 ): 95% show 1-20 bp microhomology and recombination occurs predominantly (at 93%) between nearby fragments in opposite orientations.
Features of natural recombination Between viral sequences In the FHV dataset of  Routh et al. (2015) , we found a total of 744,201 FHV-RNA1-FHV-RNA1 and 45,155 FHV-RNA2-FHV-RNA2 chimeric reads representing respectively 3,675 and 1,313 unique recombination breakpoints. We note that in spite of the differences between our approach and that of  Routh et al. (2015)  in terms of alignment method (mapping vs. blast) and criteria to detect chimeric reads, our numbers are similar to those obtained in the original study (766,143 FHV-RNA1-FHV-RNA1 and 39,856 FHV-RNA2-FHV-RNA2;   et al. 2015). Among these, very few breakpoints involved genome regions in opposite orientation (73 out of 4,988, $1. 5%), indicating that recombination occurred via a mechanism different from that underlying DENV-DENV, EBOV-EBOV and MaHV-1-MaHV-1 chimeras.
Thus, they are not informative. However, it is notable that the various within-genome chimeras we detected in datasets obtained with the Illumina Nextera library preparation kit have similar features, whether they involve RNA or DNA templates from viruses or other source material (e. g. , pillbug): (i) recombining fragments present comparable microhomology length distributions at their junction points, (ii) junction sites appear evenly distributed along molecules, (iii) distances between recombining regions of are mostly shorter than 100 pb, and (iv) chimeric reads mostly link sequences in opposite orientations. These features were not shared by FHV chimeras sequenced by the ClickSeq technology  (Routh et al. , 2015) , whose biological origin is established. Hence, the sequencing technology, rather than differences between analyzed organisms, seems to explain features of chimeric reads.
We therefore conservatively interpret Nextera-sequenced chimeras as produced during the processing of genetic material for sequencing. Because sequencing of the DNA virus MaHV-1 did not require cDNA synthesis by reverse transcription, recombination events detected in this dataset must have taken place during the PCR step of the Nextera library preparation protocol. Short recombination distances indicate that most breakpoints are generated by intra-molecular, rather than inter-molecular, recombination between close positions. Indeed, there is no reason for nearby sequences to preferentially recombine if these belonged to different molecules, considering the absence of recombination hotspots along genomes. This observation also excludes chimera production during the sequencing reaction. Such error may have arisen if the fluorescence signals generated by sequencing two different DNA fragments were somehow swapped in the course of the run.
The rates of artificial recombination we detected (Table  1 , column 3) are consistent with those previously reported  (Di Giallonardo et al. , 2013; Haas et al. , 2011; Routh et al. , 2015; Shao et al. , 2013). They further outline the necessity to identify and remove technical chimeras from high-throughput sequencing datasets obtained by techniques using PCR, before downstream analyses  (Edgar et al. , 2011; Routh et al. , 2015) , if these analyses can be affected by their presence. Fortunately, the low frequency of artificial chimeric reads (,1% of all reads) and the absence of clear recombination hotspots greatly mitigate the impact of chimeras on most analyses, such as genome sequencing and assembly, variant detection and DNA conformation analyses, as these rely on the consistency between several reads obtained from a given locus or variant.
5%). Coupled to a bias-free library preparation protocol and an internal control to test the occurrence of in vitro recombination (e. g. , mixing DNA/RNA of species that were never in contact), this distinctive feature may be useful to globally evaluate the presence of artificial recombination in datasets obtained from short-read sequencing technology. Figure  4  Model for the formation of artificial chimeras during the PCR step of the Illumina Nextera library preparation kit. Artificial chimeras most likely take place by intra-molecular template switching (TS) during extension of a primer along a double-stranded (or partially double-stranded) template. The dissociated extending strand reanneals to the displaced strand at a position upstream in respect to the direction of extension. Such reannealing is facilitated by base pairing over 1-20 bp (here, 3 bp), i.
ACKNOWLEDGMENTS We thank  Richard Cordaux  for valuable comments during the design of the study and on earlier versions of the manuscript. This work was supported by  Agence Nationale de la Recherche  Grant  ANR-15-CE32-0011-01  TransVir (to C. G. ),  Agence Nationale de la Recherche  Grant  ANR-17-ERC2-0016-01  (to L. L. ), the  French Government 's  Investissement d'Avenir program Laboratoire d ' Excellence Integrative Biology of Emerging Infectious Diseases  Grant  ANR-10-LABX-62-IBEID  (to L. L. ), the  City of Paris Emergence(s) program in Biomedical Research  (to L. L. ), the 2015-2020 State-Region Planning Contract and  European Regional Development Fund , and intramural funds from the  Centre National de la Recherche Scientifique  and the  University of Poitiers  (to J. P. and C. G.
n Table 1 Number of chimeric reads detected in all datasets analyzed in this study Type of chimeras Total number of chimeras Proportion of chimeras Ã Number of unique chimeras Total replicates 1 + 2 DENV 1-Moquito 1 350 0. 013-0. 13% 343 555 DENV 2-Mosquito 2 216 0. 007-0. 098% 212 DENV 1-Pillbug 1 2353 0. 09-0. 22% 2304 3639 DENV 2-Pillbug 2 1364 0. 05-0. 16% 1335 DENV 1-DENV 1 212644 8% 44805 81516 DENV 2-DENV 2 189633 6. 70% 36711 EBOV-EBOV 144556 7. 21% 16504 - Pillbug18S-Pillbug18S 1 20324 4. 90% 4662 817 Pillbug18S-Pillbug18S 2 14799 4. 56% 3508 MaHV-1-MaHV-1 2507 0. 12% 1139 - FHV-RNA1-FHV-RNA1 744201 2. 90% 3675 - FHV-RNA2-FHV-RNA2 45155 0. 61% 1313 -.
| Landscape and nest data In February-March 2014, we exhaustively mapped all the nests of A. dorsata in the study area. We localized the quite visible nests by visiting all forest fragments within the study zone, and by interviewing 283 planters on the presence of A. dorsata in their neighbourhood. The high nestsite fidelity of A. dorsata  (Paar, Oldroyd, & Kastberger, 2000) , combined with local farmer knowledge of nesting sites and previous mapping of nests  (Krishnan, 2011)  provided good prior knowledge of probable nest locations and allowed us to cross-check the comprehensiveness of the search. Nest locations were recorded with a Garmin GPSMAP 60CSx. To characterize the landscape patterns, we used a land cover map of the study area, extended by a buffer zone of 2 km to minimize edge effects.
ACKNOWLEDGEMENTS This work was funded by the  EU  Project  PITN-GA-2013-608422 -IDP BRIDGES "Bridging Plant Sciences and Policy " and by the contribution of  CIRAD, France. We thank the  French Institute of Pondicherry  for their support. We are grateful to all the people who helped in field work and land owners for allowing us to visit their plantations and forest plots. We thank two anonymous reviewers for their useful comments. F I G U R E 7 Synthesis  of the multiple multiscale effects of tree-covered patches (coffee plantations and forest fragment) and land cover heterogeneity on the presence of nests. The spatial arrangement of land covers, as a proxy for nesting substrate, nesting sites and foraging resources, influences both nest presence and population size at different scales [Colour figure can be viewed at wileyonlinelibrary.
Research questions and data The point of departure for this article is the observation, in the light of previous work and comments on register, medium and genre, that relatively speaking, there appears to be a noticeable presence of postposition in a recent corpus of French oral narrative -the French Oral Narrative Corpus. 16 Where Cappeau's corpus contains approximately one postposed subject every half hour, this corpus contains 292 examples in 16 hours 40 minutes, so roughly nine per half hour. The French Oral Narrative Corpus, unlike Cappeau's, is not of vernacular conversational French but of performed stories, including fairy tales, anecdotes, animal tales, fantastic tales, myths, legends and other types. It contains eighty-seven stories which have been recorded in authentic performance contexts, transcribed and annotated using the Text Encoding Initiative (TEI), for a range of structures, including postposition.