dataesr/scientific-paragraphs-categorization huggingface dataset:
Acknowledgements This work was supported by The  Netherlands Organization for Health Research and Development (ZonMw ,  Meer Kennis  met  Minder Dieren ; grant no. 40-42600-98-096 ). J. C. L. , L. B. and M. C. D. have received support from the  Netherlands Organization for Scientific Research  (grant no. 016. 126. 386 ) and the  Dutch Kidney Foundation  (grant no. C06. 6023  and  C08. 2274 ). Funders had no role in study design, data collection, analysis, writing the manuscript or decision to publish. The authors would like to thank the members of the REGaTTA cohort ( REnal GeneTics TrAnsplantation; University Medical Center Groningen, University of Groningen, Groningen, the Netherlands ):  H. G. D. Leuvink ,  H. van Goor ,  J. L. Hillebrands ,  B. G. Hepkema ,  H. Snieder ,  J. van den Born ,  M.
Genome Assemblies A 33. 6 megabase (Mb) reference genome of P. malariae was produced from clinically isolated parasites and sequenced using Pacific BioSciences long-read sequencing technology. The assembled sequence comprises 14 super-contigs representing the 14 chromosomes, with 6 chromosome ends extending into telomeres, and a further 47 unassigned subtelomeric contigs containing an additional 11 telomeric sequences (Table  1 ). Using existing Illumina sequence data from two patients primarily infected with P. falciparum, reads were extracted (Methods) and assembled into 33. 5 Mb genomes for both P. o. curtisi and P. o. wallikeri, each assembly comprising fewer than 800 scaffolds. The genomes are significantly larger than previously sequenced Plasmodium species, and have isochore structures similar to those in P.
Genome Assembly The PacBio sequenced P. malariae sample, PmUG01, was assembled using HGAP  55  with an estimated genome size of 100Mb to account for the host contamination (~85% Human). The resulting assembly was corrected initially using Quiver 55 , followed by iCORN 56. PmUG01 consisted of two haplotypes, with the majority haplotype being used for the iCORN 56 , and a coverage analysis was performed to remove duplicate contigs. Additional duplicated contigs were identified using a BLASTN 57 search, with the shorter contigs being removed if they were fully contained within the longer contigs or merged with the longer contig if their contig ends overlapped. Host contamination was removed by manually filtering on GC, coverage, and BLASTN hits to the non-redundant nucleotide database 57. Using two more samples, PocGH02 and PowCR02, additional draft assemblies of both P.
A maximum likelihood phylogenetic tree was constructed using RAxML 70 with 100 bootstraps 71 (Figure  1b ). To confirm this tree, we utilized different phylogenetic tools including PhyloBayes 72 and PhyML 73 , a number of different substitution models within RAxML, starting the tree search from the commonly accepted phylogenetic tree, and removing sites in the alignment which supported significantly different trees. All approaches yielded the final tree found in Figure  1b  with highest likelihood. Figtree was used to colour the tree (http://tree. bio. ed. ac. uk/software/figtree/). A phylogenetic tree of four P. malariae (PmID01, PmGN01, PmGN02, PmMY01) and all P. malariae-like samples (PmlGA01, PmlGA02) was generated using PhyML 73 based on all P. malariae genes. For each sample, the raw SNPs as called using the SNP pipeline (see below), were mapped onto all genes to morph them into sample specific gene copies using BCFtools 74.
Divergence Dating Species divergence times were estimated using the Bayesian inference tool G-PhoCS 19 , a software which uses thousands of unlinked neutrally evolving loci and a given phylogeny to estimate demographic parameters. One additional sample per assembly (PmGN01 for P. malariae, PocGH02 for P. o. curtisi, PowCR02 for P. o. wallikeri, and PmlGA02 for P. malariae-like) was used to morph the respective assembly using iCORN 56. Regions in the genomes without mapping were masked, as iCORN 56 would not have morphed them. Unassigned contigs and subtelomeric regions were removed for this analysis due to the difficulty of alignment. Repetitive regions in the chromosomes of the four assemblies and the four morphed samples were masked using Dustmasker 75 and then the chromosomes were aligned using FSA 76.
Reticulocyte Binding Protein (RBP) Phylogenetic Plot Full-length RBP genes were manually inspected using ACT 67 and verified to either be functional or pseudogenized by looking for sequencing reads in other samples that confirm mutations inducing pre-mature stop codons or frameshifts. All functional RBPs were aligned using MUSCLE 49 and cleaned using GBlocks 69. PhyML 73 was used to construct a phylogenetic tree of the different RBPs. Figtree was used to colour the tree (http://tree. bio. ed. ac. uk/software/figtree/).
To calculate the average Ka/Ks ratio 45 , we took the cleaned alignments of the MK test, extracting the pairwise sequences of P. malariae and P. malariae-like (and of P. o. curtisi and P. o. wallikeri). The Bio::Align::DNAStatistics module was used to calculate the Ka/Ks values for each pair 87 , averaging across samples within a species. Using existing RNA-Seq data from seven different life-cycle stages in P. falciparum 25 , reads were mapped against spliced gene sequences (exons, but not UTRs) from the P. falciparum 3D7 reference genome 2 using Bowtie2 88 v2. 1. 0 (-a -X 800 -x). Read counts per transcript were estimated using eXpress v1. 3. 0 89. Genes with an effective length cutoff below 10 in any sample were removed. Summing over transcripts generated read counts per gene. Each gene in P.
Acknowledgements This work was supported by the  Medical Research Council  [ MR/J004111/1] [MR/L008661/1 ] and the  Wellcome Trust  [098051]. S. A. and R. N. P. are funded by the  Wellcome Trust  (Senior Fellowship in Clinical Science awarded to RNP,  091625 ). F. R. , B. O. , and F. P. are financed by the  ANR JCJC 2012 ORIGIN , the  LMI Zofac , as well as by  CNRS ,  IRD , and  CIRMF. C. I. N. is funded by the  Wellcome Trust  [104792]. A. A. D. is funded as a Sanger International Fellow. The authors thank  Eric Willaume  from the  Park of La Lékédi , and the different people involved in the sanitary controls of the chimpanzees. J. S. M. and N. M. A. are supported by  NHMRC Practitioner Fellowships  (# 104072 ).
Proteome array The Proteome Profiler Human Phospho-MAPK Array Kit (R&D Systems, Minneapolis, USA) was used to screen the phosphorylation status of 26 kinases involved in cell proliferation. Procedure was performed according to the manufacturer's instructions. Briefly, protein lysate from pLKO, shKLRC3 and GBM1 were obtained using the lysis buffer provided in the kit. Protein lysates were incubated with detection antibody cocktail on membranes after saturation. Revelation was performed using chemi reagent mix. Samples were analysed with G-Box (Ozyme; Fisher Scientific). Dots intensities were determined by densitometry using ImageJ software (NIH).
This major function is confirmed by the predominant decrease in colony-forming cells following its gene silencing compared to those of PRUNE2 and CHI3L1. These datas concerning KLRC3 involvement in glioblastoma aggressiveness are supported by the decrease in tumour growth after shKLRC3 cells engraftment in vivo compared to control cells. By using public databases, we founded that KLRC3 gene expression level increased more than 1. 7 times in glioma samples compare to normal tissue (from GENT database: Gene Expression across Normal and Tumour tissue)  [15]. Moreover, in a cohort of 154 patients with glioblastoma, KLRC3 has been founded mutated in 6% of the cases. By comparing the median survival of the patients included in the cohort, we founded a strong increase from 13. 3 months for the patients without mutation to 25.
Acknowledgements This work was supported by grants from  Conseil Regional du Limousin, Ligue Nationale Contre le Cancer  ( comit es de la Creuse, Corr eze et de la Haute Vienne ),  CORC  ( Comit e d'Organisation de la Recherche sur le Cancer du Limousin) ,  ELIARE network Sudoe. This work was also supported by grants from  Mineco   SAF-2012-30862  to RSP.
Methods A self-controlled case-series study was performed on a cohort of patients with incident stroke recorded in the German Pharmacoepidemiological Research Database (GePaRD), which covers about 20 million persons throughout Germany. We estimated adjusted incidence rate ratios (IRR) by comparing the rate of stroke in risk periods (i. e. , periods following HZ) with the rate of stroke in control periods (i. e. , periods without HZ) in the same individuals, controlling for both time-invariant and major potentially time-variant confounders.
[2] [3] [4] [5] [6] [7] [8] [9]  Two cohort studies from Taiwan and Sweden observed a 1. 3 fold increased risk of any (ischemic or hemorrhagic) stroke within 12 months after HZ. [3, 8]  Another cohort study based on the Danish national registers in adults reported a 2. 3-fold increased risk in the first two weeks, a 1. 2-fold increased risk between two weeks and one year and a 1. 1-fold increased risk after the first year following HZ as compared to the baseline period. [7]  A similar temporal pattern was observed by Langan et al. in a study based on the UK Clinical Practice Research Datalink (CPRD) database in adults: the risk of stroke was 1. 6-fold increased in the first month, 1. 4-fold increased between one and three months, 1. 2-fold increased between four and six months and not increased between seven and twelve months after HZ.
[4]  A similar temporal trend was also observed in a recently published US community cohort study  where Yawn et al. found a 1. 5-fold increased risk of stroke in the first 3 months after HZ among patients aged 50+ which declined beyond 3 months. [9]  In another US study based on Medicare beneficiaries older than 65 years, the observed risks for ischemic stroke were highest in the first week after HZ (2. 7-fold increase) and decreased to baseline risk after 3 months. [6]  Breuer et al. examined also the long term effects of HZ on stroke risks in a matched cohort study based on data from the UK THIN database and found no increased risk of stroke after a median followup of 6. 3 years. [2]  The risk of stroke associated with HZ ophthalmicus (HZO) was found to be higher in studies that differentiated by HZ site.
[4, 6]  Except for age, both studies did not control for time variant confounders over a median follow-up period of 12. 5 and 5 years, respectively. It is likely that the prevalence of some major risk factors such as atrial fibrillation and flutter, transient ischemic attacks and myocardial infarctions as well as the use of antithrombotic medication and statins changed during this time span. The aims of our study were to assess the adjusted risk of stroke after HZ onset based on a large German population database and in particular the assessment of the specific risks of ischemic and hemorrhagic stroke, of the risk of stroke after HZO, and of the temporal pattern of the HZ-related risk and to examine the effect of controlling for both time-invariant and major potentially time-variant confounders.
Data source Data was obtained from the German Pharmacoepidemiological Research Database (GePaRD) which is based on claims data from four statutory health insurance providers covering over 20 million persons throughout Germany. GePaRD contains individual level information on demographic characteristics, hospitalizations (including admission diagnoses, main discharge diagnoses, and reason for discharge including death), outpatient physician visits, and outpatient drug dispensation for reimbursed products. While exact dates are provided for hospitalizations and outpatient drug dispensations, only the year and quarter are known for outpatient diagnoses. The acceptability of GePaRD for pharmacoepidemiological research has been assessed methodologically as well as by validation studies. [10] [11] [12] [13] [14] [15]  Recently, GePaRD has been used for various types of pharmacoepidemiological studies including drug utilization studies and studies investigating the risks of drugs or vaccines  [10, [16] [17] [18].
Study Population For this study, data of 7. 7 million persons from 2004 to 2011 was used, since at the time of analysis no more recent data was available. Patients of all ages were included into the study cohort if they (i) had been insured for at least 12 consecutive months between January, 2004 and December, 2011, (ii) had a diagnosis of ischemic, hemorrhagic, or unspecified stroke during the observation period, i. e. after cohort entry, and (iii) had no diagnosis of HZ or stroke within the 12 months preceding cohort entry (baseline period). Patients with HZ during follow-up were required to have an exact date of HZ onset which could only be retrieved from HZ-related admissions to hospital or from prescriptions of HZ related antiviral medication. Hence, patients whose first HZ diagnosis during follow-up was an outpatient diagnosis without accompanying prescription of systemic antiviral treatment (acyclovir, brivudin, famciclovir, valaciclovir) were excluded.
The first occurrence of the respective codes in the baseline period or during follow-up was used to define the status of the time-dependent covariable. To assess the change in prevalence of these risk factors over time, their prevalence during the baseline period as well as in the last year of the observation period was described. Codes for the vascular risk factors are available upon request. All statistical analyses were conducted using SAS version 9. 2 and 9. 3. Since the SCCS method has not yet been implemented in standard statistical software, a published macro based on the SAS-IML programming language has been used for the SCCS analysis. [20].
[23]  Although treatment percentages were comparable between immuno-compromised and immuno-competent patients as well as between patients with complicated and uncomplicated HZ, we cannot exclude that the risk of stroke might differ in HZ patients treated and untreated with systemic antivirals, which has been reported by Langan et al. Regarding the anatomical location of HZ, the data only allowed for identification of HZO which was defined based on diagnosis codes. With this approach based on diagnosis codes alone we may have missed some cases of HZO, however, we consider it to be very specific for HZO leading to a high positive predictive value. Misclassification of stroke is also possible, but previous studies in other databases have shown that ICD-10 codes of stroke usually have good positive predictive value.
gov (N°NCT02625831). The study was done in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. For SLE patients, clinical and biological manifestations as well as treatments received and disease activity evaluated using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)  [26]  at the time of sampling were recorded. The SLE patients were divided into two groups for further analyses: a group with quiescent or "low disease activity" (n = 88) and a group with active or "high disease activity" (n = 77), according to the physician in charge and respectively with a SLEDAI score 4 and >4. All patients with renal involvement had an active lupus nephritis (LN) documented by kidney biopsy (classes I, II, III, IV or V of the ISN/RPS classification)  [27]. Samples were collected just before kidney biopsy.
Statistics Data analyses were carried out using Statview software version 5. 0. Comparisons of continuous variables between subgroups were done using Mann-Whitney non parametric U-test. Correlations between continuous variables were assessed calculating Spearman's rank correlation coefficients. Comparisons of categorical variables, expressed as counts (%), were done using Chi²or Fisher's exact-tests. P-values lower than 0. 05 were considered statistically significant.
1-PS1 and mCD4. 1-HS 12 (Fig. 1A ). Formulated in HEC gel and stored at -20 °C, mCD4. 1-PS1 was also stable for one year (data not shown). Next, the molecule was prepared at 36, 144 or 600 μ M in 1. 5% HEC hydrogel in 5 mM citrate buffer pH 4. 5, 0. 1% sorbic acid and 2. 5% glycerol. These preparations (2 ml of gel) were then administrated in the vaginal cavity of anaesthetized and Depo-Provera pre-treated female cynomolgus macaques (two animals per condition), after which vaginal fluid sampling was performed at baseline, 1, 2, 4, 6, 24, 48 and 72 hours. To quantify the mCD4. 1-PS1 activity in each sample we evaluated vaginal fluid dilutions for their inhibitory potency against the HIV-1 IIIB strain. This viral strain features a very high sensitivity to mCD4. 1-PS1 (IC 50 = 0. 013 nM) compared to the other virus investigated (Table  1 ) and thus constitutes an excellent reporter of the compound activity.
1-PS1 HEC gel at the concentration of 600 μ M became infected (Fig. 2C ) resulting in a significant difference when compared to the control group (83% of protection: Fisher exact's test, p = 0. 0152). The five protected animals treated with the mCD4. 1-PS1 HEC gel at 600 μ M remained seronegative throughout the duration of the study and we confirmed that none of the protected animals had a detectable SHIV DNA in lymph nodes collected at week 9 after challenge (data not shown). For the four animals infected in the two mCD4. 1-PS1 HEC gel groups, SHIV viruses isolated from plasma were sequenced to document any evidence of resistance. No reported resistance mutations were detected and none of the isolates had the key mutation in amino acid position 375 of gp120 that was previously shown to confer resistance to mCD4 in vitro  35.
S1  and Table  S1 ). These two new peptides, mCD4. 2 and mCD4. 3 respectively, where then conjugated to PS1, giving rise to mCD4. 2-PS1 and mCD4. 3-PS1 (Supplementary information method). To quantify the affinity of these molecules for R5-or X4-derived gp120, we performed direct binding analyses in which series of concentrations of the conjugates were injected over X4-or R5-gp120 immobilized on a sensorchip. Surface Plasmon Resonance (SPR) monitoring was used to measure changes in refractive index caused by the interaction and the data were fitted to a Langmuir binding model. Results are shown in Fig. 3  and indicate that mCD4. 2-PS1 and mCD4. 3-PS1 display very high affinity for their targets with K D = 0. 098 and 0. 056 nM for HIV-1 MN gp120 and 0. 032 and 0. 038 nM for HIV-1 YU2 gp120, used as models of X4-and R5-Env respectively.
Moreover, Gag expression in target cells was due to de novo synthesis, since it was substantially reduced in the presence of nevirapine or with the broadly neutralizing antibody (bNab) targeting the CD4 binding site on Env (NIH45-46 bNAb, data not shown and  44  ). The mCD4. 1, 2 and 3 constructs inhibited HIV-1 cell-cell transmission at a high concentration: 100-1000 nM (Fig. 4A ). Strikingly, the mCD4. 1,2 or 3-PS1 constructs were much more active and blocked by more than 95% HIV cell-cell spread at 1 nM, with IC 50 = 0. 1-0. 3 nM (Fig. 4A, B ). To describe further the mechanism of action of the mCD4-PS1 constructs, we incubated HIV-1 infected cells with mCD4. 2-PS1, chosen as a representative compound of the mCD4-PS series, for a short period (10 min at 37 °C). Then we measured the levels of Env epitopes at the cell surface using the 3BNC117 bNAb that targets the CD4bs.
Subsequently, 120 μ L of supernatants were removed, 75 μ l of the luciferase substrate Steadylite (Perkin Elmer, Life Sciences, Zaventem, Belgium) were added to the wells and the plates were incubated at room temperature on an orbital shaker for 10 minutes. Next, the luciferase activity was measured using a TriStar LB941 luminometer (Berthold Technologies GmbH & Co. KG. , Bad Wildbad, Germany) and expressed in relative light units (RLU) as a percentage of positive control wells. IC 50 were calculated in GraphPad Prism 5. 03 using non-linear regression (GraphPad Software, San Diego, CA, USA).
KG. , Bad Wildbad, Germany) and expressed as relative light units (RLU) and expressed as a percentage of that in positive control wells. IC 50 were calculated in GraphPad Prism 5. 03 using non-linear regression (GraphPad Software, San Diego, CA, USA) and used to estimate the compound concentrations in CVL. Surface Plasmon Resonance based binding assay. The interactions between gp120 and its ligands were analyzed by Surface Plasmon Resonance (SPR) based methods. For that purpose, N-ethyl-N'-(diethylaminopropyl)-carbodiimide (EDC)/N-hydroxy-succimide (NHS) activated CM4 sensorchips were functionalized with either MN or YU2 gp120 as described  23  and the molecules under investigation were injected over the different surfaces. Binding responses were recorded as a function of time and analyzed by fitting both association and dissociation phases for several concentrations, using the Biaevaluation 3.
Acknowledgements This work was supported by grants from the  Agence National de la Recherche  ( ANR-10-EMMA-0012 ), the  "Agence Nationale de Rercherche sur le SIDA et les Hépatitues virales" (ANRS)  and used the platforms of the  Grenoble Instruct Centre (ISBG ;  UMS 3518 CNRS-CEA-UJF-EMBL ) with support from  FRISBI  ( ANR-10-INSB-05-02 ) and  GRAL  ( ANR-10-LABX-49-01 ) within the  Grenoble Partnership for Structural Biology  (PSB). It was also supported by the  Region Ile de France  (bpifrance,  AIMA A1412061Q ), the  Carnot-Pasteur Maladies infectieuses , the "CEA valorization" offices, the " Equipements d'Excellence" (EQUIPEX) -2010 FlowCyTech  and the " Infrastructures Nationales en Biologie et Santé " (INBS) -2011  Infectious Disease Models and Innovative Therapies (IDMIT) , funded by the " Programme investissements d'avenir"  under grant agreement N°  ANR-10-EQPX-02-01  and  N° ANR-11-INBS-0008  respectively.
Acknowledgements The authors thank  Dr. Daniel Scott-Algara  for scientific discussions. We also thank all the women who gave their informed consent,  AP-HP  ( Assistance Publique Hôpitaux de Paris ),  Anne Lebreton ,  Séverine Ballan ,  Julien Ighil  and clinical personnel for providing the samples; the  PIRC (Pole Intégré de Recherche Clinique, Institut Pasteur)  for their help with biomedical regulatory aspects of the project; the  SESAME program  for the LSRII device; the  CIH for Luminex assay (Centre d'Immunologie Humaine, Institut Pasteur).
Funding This work was supported by  ANRS  (H. Q and H. E-C financial support and Grant # 12165/13129 ),  Sidaction  (M. D and H. E-C financial support and grant #  AI20-3-01671 ), the  TOTAL Foundation, INSERM , and the  Institut Pasteur. Received: 22 December 2015 Accepted: 23 May 2016.
Sanger sequencing confirmed that the two siblings were homozygous and the parents and healthy siblings were heterozygous for this mutation (Fig. 1 C ). This mutation was not found in the 1000 Genomes, National Heart, Lung, and Blood Institute exome sequencing project, and Exome Aggregation Consortium databases or in 251 Iranian blood donors and our recent study of the Middle Eastern Variome  (Scott et al. , 2016). The mutation is predicted to be deleterious (for details, see the Genetic analysis section of Materials and methods). In family 2, whole-genome sequencing (WGS) was performed on the affected sibling (P4) and both parents. We used a similar strategy to family 1 for filtering and prioritizing variants and identified a novel homozygous 3-bp deletion (c. 555_557delCTT), also located in exon 3 of CD70, predicted to be deleterious and cause an in-frame deletion at position 186 (p.