dataesr/scientific-paragraphs-categorization huggingface dataset:
SBA and ABA ancestries were detected in Italian and non-Italian best proxies (Figs. 2D  and 3  and data file S5), which suggests that part of these ancestries arrived from outside Italy in historical times  (21) , but also that these components were already present in Italian groups at the time of these admixture events. The timing of the admixture events and the sources involved differ between Northern and Southern Italian clusters, pointing to different admixture histories for the two areas. Episodes of gene flow were also detected in Sardinia, combining signals from both the African continent and North-West Europe. MALDER results for the more recent episodes replicated the admixture pattern identified by GT (fig. S8  and data file S5). (27). The 50 genes containing NTT SNPs were enriched for phenotypes related to facial morphology, body size, metabolism, and muscular diseases (Materials and Methods, Supplementary Materials, and data file S6).
Analysis of modern samples Dataset Two hundred twenty-two samples are presented here. Of these, 167 Italians and 6 Albanians were specifically selected and sequenced for this project with two versions (1. 2 and 1. 3) of the Infinium Omni2. 5-8 Illumina beadchip, while 49 Italians and Europeans were genotyped with the Human660W-Quad BeadChip in the frame of another research (data file S1)  (35). Two separate worldwide datasets were prepared. The FMD included 4852 samples  (2, 12, 22, (36) (37) (38) (39) (40) (41) (42) (43) (44) (45) (46) (47) (48) (49) (50) (51)  (1589 Italians) and 218,725 SNPs genotyped with Illumina arrays; the HDD contained 1651 samples  (12, 36, 38, 40, 44, 47, 50, 51)  (524 Italians) and 591,217 SNPs genotyped with the Illumina Omni array (Supplementary Materials). The merging, the removal of ambiguous C/G and A/T and triallelic markers, the exclusion of related individuals, and the discarding of SNPs in LD were performed using PLINK 1.
Haplotype analysis (CP and fS) We investigated patterns of genetic differentiation in Italy by exploring the information provided by SNP-based haplotypes. Phased haplotypes were generated using SHAPEIT 2  (53)  and by applying the HapMap b37 genetic map. CP was used to generate a matrix of recipient individuals "painted" as a combination of donor samples (copying vector). Three runs of CP were done for each dataset generating three different outputs: (i) a matrix of all the individuals painted as a combination of all the individuals, for cluster identification and GT analysis; (ii) a matrix of all Italians as a combination of all Italians, for F ST analysis; and (iii) a matrix of all the samples as a combination of all the other samples but excluding Italians, for noItaly GT analysis. The median numbers of SNPs per painted fragment were 13.
F ST estimates among clusters Pairwise F ST estimates among newly generated Italian clusters and originally generated European clusters (Supplementary Materials) were inferred using the smartpca software implemented in the EIGENSOFT package  (54). Comparisons between the F ST distributions were performed using a Wilcoxon rank sum test in the R programming language environment. Principal components analysis PCA was performed on the CP chunkcount matrix (Supplementary Materials) and was generated using the prcomp() function on R software. Allele frequency PCA was performed using smartpca implemented in EIGENSOFT (54) after pruning the datasets for LD.
Characterization of the migration landscape (EEMS analysis) We highlighted the spatial patterns of genetic differentiation by EEMS analysis  (19). This was performed estimating the average pairwise distances between populations using the bed2diffs tool, and the resulting output was visualized using the Reems package  (19). ADMIXTURE analysis ADMIXTURE 1. 3. 0 software (55) was used, performing 10 different runs using a random seed. The results were combined with CLUMPAK (56) using the largeKGreedy algorithm and random input orders with 10,000 repeats. Distruct for many K's implemented in CLUMPAK  (56)  was then used to identify the best alignment of CLUMPP results. Results were processed using the R statistical software.
The time and the sources of admixture events (GT and MALDER analyses) Times of admixture events were investigated using the GLOBE-TROTTERv2 software. GT was utilized using two approaches: complete and nonlocal (referred to as noItaly; Supplementary Materials) in default modality  (2, 11). The difference between the two approaches was the inclusion or the exclusion respectively of all the Italian clusters as donors in the CP matrix used as the input file. To improve the precision of the admixture signals, the "null. ind: 1" parameter was set  (2). Unclear signals were corrected using the default parameters, and a total of 100 bootstraps were performed. MALDER  (57)  uses allele frequencies to dissect the time of admixture signals. The best amplitude was identified and used to calculate a Z score (Supplementary Materials).
Comparison of Neanderthal allele frequencies across modern populations We explored significant differences in the frequencies of Neanderthal alleles across populations by computing the allele frequency differences for every SNP for each of the possible pairs of the 11 populations in our dataset, thus obtaining 55 distributions (see the Supplementary Materials). Then, the NTT SNPs, i. e. , the Neanderthal-tag SNPs in the top 1% of each distribution, were selected (data file S6).
The biological implications of Neanderthal introgression Given the list of genes overlapping the Neanderthal introgressed regions harboring the NTT SNPs and the list of genes directly harboring the NTT SNPs, we performed different enrichment tests with the online tool EnrichR  (63). Particularly, we searched for significant enrichments compared to the human genome using the EnrichR collection of database, e. g. , dbGaP, Panther 2016, HPO, and KEGG 2016 (data file S6). We then investigated known direct associations between the Neanderthal alleles of the NTT SNPs and phenotypes by looking in the GWAS and PheWAS catalogs (https://phewascatalog. org/phewas) and applying the PheGenI tool (https://www. ncbi. nlm. nih. gov/gap/phegeni) (data file S6). We used the circos representation as in  Kanai et al.
The obtained sequences of the three fragments were analyzed using 4Peaks software (version 1. 8, Mekentosj, Lisbon, Portugal) and assembled into a consensus sequence using Mega7 software (Pennsylvania State University, State College, PA). 20 he three RT-PCR assays for Env amplification (Env RT-PCRs) were performed on RNA directly extracted from the dilutions of the DENV1 isolate. Successful amplification was obtained for all dilutions, except the last one, 10 -6 (Table  2 ). The DENV1 isolate dilutions 10 -3 , 10 -4 , and 10 -5 were then Preliminary experiments (data not shown) were performed to determine the optimal primer and MgSO4 concentrations and annealing temperature for each primer set. Optimal conditions resulting from those experiments are displayed in the table. The thermal cycling consisted of 45°C for 45 minutes, 94°C for 2 minutes, 40 × (94°C for 30 seconds, annealing temperature for 1 minute, and 68°C for 2 minutes), and 68°C for 7 minutes.
Acknowledgments: We are very grateful to the patients and to Assoc. Prof. Bounthaphany Bounxouei , director of  Mahosot Hospital ; to Assoc. Prof. Bounnack Saysanasongkham , director of  Department of Health Care, Ministry of Health ; to  H. E. Assoc. Prof. Bounkong Syhavong , minister of health, Lao PDR; to the staff of the  Infectious Disease Center and Microbiology Laboratory , especially  Viengmon Davong ,  Mayfong Mayxay ,  Vilada Chansamouth ,  Koukeo Phommasone , and  Sayaphet Rattanavong ; to the  Institut de Recherche pour le D éveloppement (IRD) ; and to the staff of the  Unit é des Virus Émergents  for their very kind help and support. Financial support: This study was funded by the  Wellcome Trust of Great Britain , the  Institute of Research for Development, and Aix-Marseille University.
Statistical analysis The number of animals was approved by the Ethics Committee for Animal Research of the university. Statistical analysis was performed with GraphPad Prism 5 (GraphPad Software, La Jolla, CA, USA). Normal distribution of the variables was confirmed by the ShapiroeWilk test. Interindividual comparison was assessed using the paired t test. Inter-individual comparison was assessed with a one way ANOVA test. Results are expressed as means and standard deviation. A p value <. 05 was considered to be statistically significant.
Another limitation is the small sample size. However, normally distributed continuous data results with small variance between animals in the same groups coupled with valid within animal data pairing statistics provided very high probabilities of rejecting the null hypothesis. Consequently, significant conclusions may be drawn from the data despite small sample size. Another important point is that fast glycolytic muscles were specifically investigated. This choice was based on the fact that muscle susceptibility to ischaemia/reperfusion injury depends on fibre type specific antioxidant level, explaining the greater injuries observed in glycolytic than oxidative muscles. 23 Muscle impairment had to be observed in order to determine eventual protection by NAC. Thus, the data apply only to glycolytic muscles, but this is pertinent since they are key targets to protect.
Funding and Disclosure This work was supported by the  Institut Pasteur ,  Centre National de la Recherche Scientifique   UMR 3571 , Fondation pour la recherche en alcoologie,  Fondation de la Recherche Médicale  ( SPF20140129365  and  DPA20140629803 ),  Agence Nationale de la Recherche (ANR) ,  Neuroscience and BLANC, LABEX BIO-PSY ,  FP7 ERANET program NICO-GENE  grant agreement convention  ANR  n°  2010-NEUR-004-01 ,  European Commission   FP7   RTD  Project  HEALTH-2009-Neurocyp. 08-202088  grant  242167 ,  French National Cancer Institute  grant  CANCEROPOLE IDF 2016-1-TABAC-01-IP-1   MASKOS ,  ANR  programme  SNP-NIC, European ERANET programme  iPS&BRAIN (all to U. M. ). The laboratory of U. M. is part of the  Ecole des Neurosciences de Paris Ile-de-France RTRA network. U. M. is a member of the  LABEX BIO-PSY.
Statistical analyses We did not compute or predict the number of samples necessary for statistical differences because the standard deviation of our study's population was not known before starting our analysis. Biological replicate corresponds to the analysis of different embryos of the same stage. Technical replicate corresponds to the analysis of the same embryo imaged the same way. The sample size (biological replicate and number) to use was as defined by our ability to generate our datasets. For analyses between two groups of embryos, differences were considered statistically significant when the p-value<0. 05, as determined using a two-tailed and paired Student's t-test (klf2a and notch reporter expression). For boxplots, center lines show the medians, crosses show the means, box limits indicate the 25th and 75th percentiles as determined by R software; whiskers extend 1.
Acknowledgements We thank the  Vermot laboratory for discussion  and  H Fukui  and  R Chow  for thoughtful comments on the manuscript. We thank  C Burns ,  V Lecaudey  and  I Drummond  for providing antibodies, mutants and protocols for immunohistochemistry. We thank  J-M Garnier  for the cloning of the piezo1:nls-Venus construct. We thank the  IGBMC fish facility  ( S Pajot  and  C Moebs ) and the IGBMC imaging center, in particular  B Gurchenkov ,  D Hentsch ,  E Guiot  and  E Grandgirard. This project has received funding from the  European Research Council (ERC)  under the European Union's  Horizon 2020 research and innovation programme :  GA N˚682939 , the  Fondation pour la Recherche Medicale :  DEQ29553 ,  Agence Nationale de la Recherche :  ANR-15-CE13-0015-01 ,  ANR-10-IDEX-0002-02 ,  ANR-12-ISV2-0001-01  and  ANR-10-LABX-0030-INRT  and the  European Molecular Biology Organization Young Investigator Program.
Purpose: This study assessed therapy persistence in patients with chronic obstructive pulmonary disease (COPD) in France, and the impact of non-persistence on exacerbations and described COPD-related healthcare resource use (HRU). Methods: Patients aged ≥45 years who received ≥1 dispensed bronchodilator per quarter over three consecutive quarters between 2007 and 2014 and initiated specific COPD therapy were selected from the Echantillon Généraliste des Bénéficiaires (EGB) database. Persistence, defined as the absence of dispensing gaps of >90 days, was measured at 12 months. Exacerbations were compared between persistent and non-persistent patients during follow-up after patient matching and adjustment for confounding factors. COPD-related HRU during follow-up was described. Results: Among 4020 patients with COPD, 2164 initiated a specific therapy.
Study Design and Data Source This observational cohort study was conducted using the Echantillon Généraliste de Bénéficiaires (EGB) database. The EGB database contains a representative sample (1/ 97 th ) of the population covered by the French healthcare system (including approximately 66 million individuals), which records individual anonymous information from primary and secondary care institutions (data from the French Diagnosis Related Group-based medical information system [PMSI]), and currently covers more than 90% of the French population. 18, 19 The EGB database contains general characteristics (sex, year of birth, month and year of death where applicable, and free-access-to-care status [where 100% of healthcare expenses are covered for individuals whose financial resources are below a set threshold]), residence, long-term disease (LTD) status (full coverage for all medical expenses for patients registered with LTD status), all non-hospital reimbursed healthcare expenditures with dates and codes (visits, medical procedures, laboratory tests, drugs, and medical devices, but not the corresponding medical indications or results), and hospital discharge summaries (ICD-10 diagnosis codes for all medical, obstetric, and surgery hospitalizations with the date and duration of hospitalization, medical procedures, hospital department, and cost coding system).
The first 12-month period after the index date, termed the "exposure period", was used to assess therapy persistence status. The next 12-month period, termed the "follow-up period", was used to assess the impact of persistence on subsequent exacerbations and HRU (Figure  1 ). The population in which exacerbations and HRU were studied corresponded to a subgroup of patients, whose index date was between 2007 and 2013 and who had at least 24 months of follow-up available in the database. Sociodemographic factors (age on the inclusion date, sex, and free-access-to-care status) were described at baseline, and clinical characteristics (presence of LTD status or hospitalization for COPD, comorbidities [identified by LTD or COPD-related hospitalizations], visits to primary care practitioners, visits to hospital practitioners and/or to respiratory physicians in private practice, number of COPD inhalers, use of oxygen therapy and/or noninvasive ventilation [NIV], and pulmonary function testing [PFT]) were examined over the exposure period.
Results Of the 4020 patients with COPD identified in the EGB database after application of the selection algorithm, 2164 patients initiated COPD treatment after the inclusion date (Figure  2 ). Demographic and clinical characteristics for these patients are described in Table  1. Patients had a mean age of 66. 0 years and most patients were male (60. 0%). The most common comorbidity was cardiovascular disease (72. 6%). Among the included patients, 2. 3% were hospitalized at least once, with COPD as the main diagnosis, and 7. 8% had COPD LTD status, during the exposure period. In the same period, 70. 3% of the patients visited their GP more than four times, 36. 7% had at least one contact with a respiratory physician or a hospital practitioner, and 28. 7% underwent PFT. Also during this period, 30   2 ).
According to the more restricted definition of persistence in the sensitivity analysis, patients exhibited less persistence with ICS/twice-daily LABA (the proportion of persistent patients decreased from 39. 4% to 30. 1%) and twice-daily LABA (from 46. 1% to 37. 6%) than with the other treatments studied. The smallest decrease in the proportion of persistent patients was observed with ICS (from 25. 6% to 20. 3%) (data not shown). The population in which exacerbations and HRU were studied corresponded to a subgroup of patients, whose index date was between 2007 and 2013 and who had at least 24 months of follow-up data available in the database (N=1784, consisting of 797 persistent and 987 nonpersistent patients). To render the comparison as robust as possible, 1442 patients (721 comparable pairs of persistent/non-persistent patients) were matched (Figure  2 ).
11 Furthermore, unlike the United States, where Medicare gathers data from a targeted population, the EGB claims database contains data representative of the whole population since the French healthcare system is universal. In the review by van Boven et al, there was a clear association between non-adherence to COPD medication and poor clinical and economic outcomes. 12 owever, adherence was measured as PDC and persistence per se was not studied. Of note, ICS alone does not have marketing authorization for COPD in France; rather, it is only authorized as part of an FDC. Nevertheless, our data suggest the presence of inappropriate prescribing in a limited proportion of patients (6. 3%). Matching was performed to evaluate the impact of nonpersistence on exacerbations, thus making persistent patients and non-persistent patients as comparable as possible.
Limitations There are several limitations to this study. As is often encountered for database analyses, this study could not use validated medical diagnoses of COPD or clinical or technical results (such as spirometry data). Nevertheless, proxies, such as COPD therapy use over three consecutive quarters, were used to identify the condition, an approach that has been used in other COPD studies. 30 The actual Median (IQR) 1 (1-1) 0 (0-0) 1 (1-1) 0 (0-0) Min -Max 1-4 0 -4 1 -3 0 -3 Notes: *All: patients with or without exacerbation during the year. **Adjusted for the following confounding factors: number of COPD treatments, presence/absence of an LTD or COPD-related hospitalization, number of visits to a GP, occurrence of ≥1 visit to a respiratory physician in private practice or to a hospital practitioner (regardless of specialty), presence/absence of comorbidities (cardiovascular diseases, depression, cancer and diabetes), use or non-use of oxygen therapy, use or non-use of NIV.
Acknowledgements We thank the  French National Health Service  ( Caisse Nationale de l'Assurance Maladie ) and the  National Institute of Health Data (Institut national des Données de Santé)  for providing the data. We also thank  Gaëlle Le Moine  for the coordination of the manuscript development. This study was funded by  GlaxoSmithKline plc. (study  HO-16-17431 ).
Time-lapse images were recorded on a fully automated Leica SP5 confocal microscope (Leica Microsystems, Mannheim, Germany) equipped with an Apo 63 x NA 1. 4 oil immersion objective using a proprietary macro for auto-focusing and multi-position imaging. The microscope stage was maintained at 37 C and CO2 at 5%. Apoptotic cells were identified by monitoring irreversible cell blebbing and fragmentation of cell nuclei. The area of cell adhesion and CD95-GFP clusters were detected by morphological identification and intensity threshold. Images were analyzed using ImageJ/Fiji (NIH,USA) as well as routines written in MATLAB (R2013b, The Math Works Inc, MA, USA) following cell segmentation scripts  (Monzel and Mo ¨hl, 2016).
ACKNOWLEDGMENTS We thank the  Nikon Imaging Center at the University of Heidelberg  for providing assistance in their imaging facility. We thank  Katrin Volk  for technical support. Histology services for tumor pathology analysis were provided by the  Institute of Pathology, University Hospital Heidelberg. We thank the  DKFZ Mass Spectrometry Core facility  for mass spectrometry analysis. This research was supported by  German Research Foundation ,  DFG/Transregio 186  ( TRR186 ) (to A. M. -V. ), and  DFG/Sonderforschungsbereich 873  ( SFB 873 ) (to A. M. -V. and M. T. ). M. T. thanks the  Nakatani Foundation  for support. C. M. is grateful for the financial support of the  Excellence Cluster Cell Networks and Fonds der Chemischen Industrie. This work was funded by the  German Cancer Research Center (DKFZ)  and the  Helmholtz Alliance PCCC (HGF).
Study design and sampling (sample 1) This cross-sectional study was carried out between April 2017 and August 2018. It enrolled 789 residents of the community randomly selected from Lebanon's Mohafazat in a proportionate rate. The Mohafazat are divided into Caza (stratum), divided into villages. Two villages per Caza were chosen; households were chosen in each village according to a random sampling technique  [19]. All adults living in the household were invited to participate. Those accepting to enroll in the study completed the survey through a face-to-face interview. Excluded were those with self-reported mental illness or dementia, and those who refused to complete the questionnaire. Data collection was performed by study-independent clinical psychologists whose role was to rule out psychiatric problems in each participant.
Data collection and measurement The questionnaire was prepared in Arabic, Lebanon's native language, and required 15 to 30 min to be completed. It comprised different elements: the first part consisted of sociodemographic features (gender, age, region, marital status, etc. ). The socioeconomic level was divided into 3 categories: low, intermediate and high ranging from less than 1000 USD to 2000 USD. The second part included questions hypothesized to be factors associated with insomnia (personal/family history, presence of chronic pain, etc. ). Since cigarette and waterpipe (WP) dependence are known to increase markedly the likelihood of insomnia  [31] , we decided to use the Fagerstrom scale  [32]  and the Lebanon Waterpipe Dependence Scale (LWDS-11)  [33]  to assess dependence to cigarette and waterpipe smoking respectively.
Few linguistic modifications were done before the launching of the data collection. Clarity of the questionnaire Flesch reading-ease was calculated to evaluate the ease of reading and clarity of the LIS-18 scale's questions. The score, obtained directly from the Word document, is based on the average number of syllables per word and the average number of words per sentence. It ranges from 0 to 100, with higher scores indicating an easier document to comprehend  [44]. Usually, the average Flesh score obtained for standard writing varies between 60 and 70.
Statistical analysis Statistical analysis was performed using The Statistical Package for Social Sciences (SPSS) software version 23. The distribution of our sample was normal (verified by the Shapiro Wilk test). The Pearson's test were used to assess the correlation between two continuous variables. According to Cohen, d = 0. 2 would be considered as a small effect size, 0. 5 represents a 'medium' effect size and 0. 8 a 'large' effect size  [45]. A p-value of less than 0. 05 was considered significant. A principal component analysis was initiated to confirm the validity of the construct of the LIS-18 questionnaire in the Lebanese population; we selected to use a promax rotation since the extracted factors were found to be significantly correlated  [46]. The Kaiser-Meyer-Olkin (KMO) measurement of sampling adequacy and Bartlett's sphericity test were appropriate.