dataesr/scientific-paragraphs-categorization huggingface dataset:
The prevalence of PPH (defined as ≥500 mL blood loss) and severe PPH (defined as ≥1 000 mL blood loss) are reported to be around 6. 0 and 1. 86 % of all deliveries, respectively, and vary widely throughout the world  [23]. Most estimates are calculated from observational studies that use administrative or medical birth databases  [14, [17] [18] [19] [24] [25] [26] [27] [28] [29] ; only a few come from prospective observational studies  [15, 20, 30]. Of the two French population-based studies  [20, 31] , only one was prospective, conducted in 16 of the 33 maternity units of the Rhône-Alpes perinatal network in 2004-2005  [20]. The overall incidence of immediate PPH was 5. 4 ± 0. 3 %, but the diagnosis was clinical in 82. 5 % of the severe cases and in 77. 5 % of milder ones; the remainder were detected by postpartum laboratory tests  [20].
Data source We contacted 43 French perinatal networks to request their support for this study of their maternity units. Twenty perinatal networks, covering 231 eligible maternity units, agreed to support this 6-month project (1 February 2011 to 31 July 2011). Finally, 182 maternity units participated, for a participation rate of 78. 79 % maternity units (84 level I, 69 level II and 29 level III). In 10 perinatal networks (50 % of those participating), all of the network's maternity units participated. Table  1  compares the characteristics of the French maternity units that participated and those that did not. In each case of postpartum hemorrhage (defined as blood loss >500 mL for vaginal delivery and >1000 mL for cesareans in the 24 h after delivery), the medical and/or surgical treatment and maternal outcomes were recorded.
Blood loss was to be estimated visually with the habitual method used in each unit and specified in each woman's records. Professionals in each unit collected data prospectively for 6 months, entering it onto electronic case report forms via a secure website. The principal endpoint was the incidence of PPH. Quality control was performed in 30 % of the maternity units in each participating network, selected by random drawing, from September 2011 to November 2012. In each of the selected maternity wards, 10 % of the study files (again, randomly selected) were verified manually as were the birth registers, either by a supervisor of the perinatal network or by one of the two midwives coordinating the study nationwide. One maternity ward was excluded from the statistical analysis because it refused to participate in the quality control procedure.
Oxytocin is the agent used most frequently, even after cesareans. The percentage of active management of the third stage of labor has increased in France since 2006  [45]. It is probable that the national rate in 2015 is still better, after the 2014 publication of the updated French guidelines. Our results are consistent with those from a database collecting information regularly from volunteer French maternity units  [46]. Unsurprisingly, uterine atony was the most common cause of PPH both for vaginal and cesarean deliveries (Table  4 ), but our results highlight the frequency of multiple causes in the same patient. The third leading cause of PPH after vaginal delivery was perineal tears or lacerations, and the fourth leading cause episiotomies. Episiotomies remain relatively common in France, with an overall rate around 28.
Acknowledgements ' HERA GROUP :  Bernard Branger, MD , is a pediatrician; Laure Connan, MD, is an obstetrician-gynecologist; Catherine Crenn-Hébert, MD, is an obstetriciangynecologist;  Caroline Da Costa Correia  is a midwife;  Michel Dreyfus, MD, PhD , is a professor in obstetrics and gynecology;  Paul Lefèvre, MD , is an obstetrician-gynecologist;  Anne Legrand, MD , is a statistician.
Statistical analysis The different analyses were performed using the StatView 1 software. Qualitative variables were reported as absolute and relative frequencies (expressed in %) and compared using Fisher's exact test. Quantitative variables were described by mean and standard deviation and median and interquartile range and were compared by Student's t-test. In case of a non-normally distributed variable (assessed by a Shapiro-Wilk test), a Mann-Whitney U-test was performed. Group comparability between patients with a PVP and patients presenting no PVP was verified on the demographics and baseline characteristics. We also used Spearman's rank-order correlation to elucidate a linkage between placental volume and D-dimer and between placental volume and sEPCR with their corresponding regression graphs.
Methods Isolate details. Six MTBC isolates were cultivated from sputum samples collected from newly diagnosed pulmonary TB (PTB) patients attending selected health centres and hospitals in various districts of Amhara Region, Ethiopia. The isolates were part of 237 Mtb isolates collected between 2008 and 2010 for the TB Rapid Test project at the Norwegian Institute of Public Health (NIPH). Bacteriological and molecular characterization of the strains was performed in Ethiopia, Norway and The Netherlands. Prior to sputum collection, socio-demographic and clinical data were obtained using a structured questionnaire. HIV testing was also performed on blood samples obtained from study participants following the routine procedure in Ethiopia. Sputum smear microscopy, culture and drug susceptibility testing.
, 2013). The International Spoligotype Database (SpolDB4, 2011) was used to assign the spoligotyping patterns to major genetic lineages and sub-lineages  (Brudey et al. , 2006). New spoligo patterns that were not described by SpolDB4 were assigned to Mtb families by SpolDB3 and a randomly initialized model (Run SPOT-CLUST, 2011). MIRU-VNTR typing. Mycobacterial interspersed repetitive units (MIRU) variable number of tandem repeats (VNTR) typing was performed at NIPH in Oslo, Norway to improve the discrimination of Mtb isolates and to compare the results with the extended collection of VNTR profiles of strains collected within The Netherlands. VNTR is based on the identification of 24 of the most polymorphic microsatellite sequences (55-72 nucleotides in length) in the Mtb genome  (Supply et al.
Sequencing, assembly and variant calling. Among the six isolates transferred to RIVM for whole-genome sequencing, one (Solo 80) could not be subcultured despite repeated attempts. DNA was thus extracted from five isolates using standard methods. Whole-genome sequencing was successfully performed by BaseClear BV (Leiden, The Netherlands) on an Illumina HiSeq 2500 instrument using reads of 50 bp in length in the pairedend modus. The average genome coverage was approximately 60-fold. The FASTQ sequence reads were generated using the Illumina Casava pipeline version 1. 8. 3. Initial quality assessment was based on data passing the Illumina Chastity filtering. Subsequently, reads containing adapters and/or PhiX control signals were removed using an in-house filtering protocol. The second quality assessment was based on the remaining reads using the FASTQC quality control tool version 0.
10. 0. The quality of the FASTQ sequences was enhanced by trimming off low-quality bases using the 'Trim sequences' option of the CLC Genomics Workbench version 6. 5. The quality-filtered FASTQ sequences were assembled using Ray, and the resulting contigs were mapped to both Mycobacterium tuberculosis H37Rv (GenBank accession no. NC_000962. 3) and Mycobacterium africanum GM041182 (GenBank accession no. FR878060. 1). In parallel, single nucleotide polymorphisms (SNPs) and INDELS (insertions or deletions) were called using Breseq software (version 0. 23) with a minimum depth of 15 x  (Barrick et al. , 2009). SNPs with low-quality evidence (i. e. possible mixed read alignment) or within five base pairs (bp) of an INDEL were discarded. Reads and assembled scaffolds are deposited in the European Nucleotide Archive (study accession number PRJEB8432).
Phylogenetic tree reconstruction and comparison of sequences. A parsimony-based phylogeny (Phylip, version 3. 695) of the MTBC was reconstructed using 78 613 concatenated variable positions (SNPs) that were found in at least one of 100 previously characterized RIVM strains of different lineages and the five strains from Ethiopia in relation to the outgroup strain Mycobacterium canettii CIPT 140070010 (strain STB-K; GenBank accession no. NC_019951. 1). This strain was previously determined to be the most genomically distant relative to the core members of the MTBC  (Supply et al. , 2013; Blouin et al. , 2014; Boritsch et al. , 2016). Two additional lineage 7 strains (Percy 256 and Percy 556) from an independent study were added to this tree  (Blouin et al. , 2012). The Artemis Comparison Tool (ACT)  (Carver et al.
Discussion Mycobacterium tuberculosis, a member of the MTBC, has been a significant cause of morbidity and mortality among humans for thousands of years. Phylogenetic studies have shown that the MTBC comprises at least seven distinct lineages distributed in different geographical locations around the world. Current evidence indicates that the Horn of Africa is the most likely origin of MTBC from which it has spread to other parts of the world  (Comas et al. , 2013). Ethiopia is a country in the Horn of Africa with an estimated TB incidence of 224 cases/100 000 population  (Global Tuberculosis Report, 2014). Molecular typing of isolates from various regions indicates that all major MTBC lineages are represented among TB patients in Ethiopia. A recent study conducted in the Amhara Region of Ethiopia identified a high proportion of ' Unknown' spoligotype patterns (SIT910 and SIT1729) in addition to strains not previously described in the database  (Yimer et al.
(2013). The inclusion of the phylogenetically most distant M. canettii strain STB-K (CIPT 1400700100)  (Supply et al. , 2013; Blouin et al. , 2014; Boritsch et al. , 2016)  as the outgroup has reinforced the clusters observed among the different Mtb. We found four newly identified deletions characteristic of all five lineage 7 strains from the Amhara Region and the Percy256 strain. Our study also provides additional information on the genetic heterogeneity of Mtb lineage 7 strains. The strains in our dataset were found to be more heterogeneous (average of 183 SNPs ranging from 113 to 265) than the two Percy (256 and 556) strains described in  Blouin et al. (2012)  that differed by only eight SNPs. While  Firdessa et al. (2013)  identified lineage 7 strains in the Woldiya area, we showed that lineage 7 strains also circulate in other parts of the Amhara Region and among foreign-born patients from the Horn of Africa residing in The Netherlands.
Panobinostat is an oral pan-histone deacetylase inhibitor developed by Novartis. Panobinostat acts via epigenetic modification and inhibition of the aggresome pathway. In August 2015, the European Commission authorized panobinostat for use in combination with bortezomib and dexamethasone for the treatment of relapsed or relapsed and refractory multiple myeloma (MM) in patients who have received C2 prior regimens including bortezomib and an immunomodulatory drug. In January 2016, the National Institute for Health and Care Excellence recommended panobinostat for use in the same combination and patient population. The authorization and recommendation were based on results from the pivotal phase 3 PANORAMA 1 (NCT01023308) clinical trial, which demonstrated an improvement in median progression-free survival of 7.
Bortezomib Bortezomib was the first PI to be authorized for the treatment of MM by the EC (Table  1 ). Bortezomib is a boronic acid analog that reversibly binds and inhibits the chymotryptic activity of the 20S proteasome subunit  [14]. In the phase 3 APEX trial (NCT00048230), bortezomib was superior to dexamethasone for the treatment of MM that had relapsed after 1-3 previous therapies (Table  2 )  [15]. Patients treated with bortezomib had a significant increase in overall response rate (ORR; 38% vs 18%; P\0. 001), a significantly prolonged time to progression (TTP; 6. 2 vs 3. 5 months; P\0. 001), and a significant overall survival (OS) benefit (80% vs 66% at 1 year; P = 0. 003) (Table  2 ).
One study showed that a DACi (panobinostat) reactivated genes repressed by the hypermethylation of H3K27 by the Polycomb group proteins and reduced proliferation and increased apoptosis in human MM cell lines [64]. Additionally, panobinostat led to gene upregulation, reduction of tumor load, and increased OS in preclinical models [64]. Likewise, upregulation of genes following treatment of MM cell lines with DACi correlated with increased OS [67]. Interestingly, the antimyeloma activity of DACi was found to occur largely through inhibition of HDAC1, an event necessary for maximal MM cell death [68]. Based on these and other preclinical findings, several DACi are being evaluated in clinical studies as therapeutic options in MM. Vorinostat, a panDACi, has shown clinical efficacy in combination with bortezomib in patients with RRMM in the VANTAGE-088 phase 3 randomized study (NCT00773747) [69].
0001 NR vs 7. 3 P\0. 0001 BTZ bortezomib, CFZ carfilzomib, DARA daratumumab, Dex dexamethasone, ELO elotuzumab, NA not available, NR MM multiple myeloma, LEN lenalidomide, not reached, TTP time to treatment POM pomalidomide, ORR overall response rate, OS overall survival, PAN panobinostat, PFS progression-free survival, progression, IMiDs immunomodulatory drugs, PI proteasome inhibitors, MO month, HR hazard ratio P = 0. 106) than pomalidomide-dexamethasone in patients with lenalidomide-refractory MM. A new study evaluating the combination of pomalidomide and dexamethasone with low-dose, twice-daily cyclophosphamide is currently enrolling (NCT02176213). Pomalidomide is also being evaluated in combination with low-dose dexamethasone and bortezomib. This combination showed promising activity (ORR, 71%) and good tolerability in a phase 1 dose-escalation study in patients with RRMM [35] and is now being assessed in the global, randomized, phase 3 MM-007 study (OPTIMISMM; NCT01734928) [36].
However, in the phase 3 ELOQUENT-2 trial (NCT01239797), the addition of elotuzumab to the backbone of lenalidomide and dexamethasone in patients with 1-3 prior therapies led to a prolonged median PFS [19. 4 vs 14. 9 months; HR, 0. 70 (95% CI, 0. 57-0. 85); P\0. 001] and increased ORR (79% vs 66%; P\0. 001) compared with lenalidomide and phagocytosis, and apoptosis [43-45]. In contrast to elotuzumab, daratumumab has demonstrated clinical efficacy as a single agent in heavily treated patients with RRMM. In the phase 2 SIRIUS trial (NCT01985126), patients who had received C3 prior regimens, including a PI and an IMiD, were treated with daratumumab monotherapy. In this very heavily pretreated and highly refractory population, daratumumab demonstrated an ORR of 29% with a median PFS of 3. 7 months and a median OS of 17.
5 months (Table 2) [46]. In the dose-escalation phase 1/2 study GEN 501 (NCT00574288), daratumumab demonstrated clinical efficacy in patients with RRMM who were refractory to C2 prior lines of therapy. In the dose-expansion part of the study, patients received 8 mg/kg (n = 30) or 16 mg/kg (n = 42) of daratumumab. The ORR was 36% in the cohort that received 16 mg/kg and 10% in the cohort that received 8 mg/kg. The estimated median PFS was 5. 6 and 2. 4 months in patients who received 16 and 8 mg/kg, respectively. The OS rate at 12 months was 77% in both cohorts [47]. An updated pooled analysis of 148 patients.
ACKNOWLEDGMENTS No funding or sponsorship was received for this study, publication of this article or the versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): a randomised, open-label, phase 3 trial. Lancet Oncol. 2013;14:1055-66. 32. Dimopoulos MA, Weisel KC, Cavo M, et al. The STRATUS trial (MM010): a single-arm phase 3b study of pomalidomide plus low-dose dexamethasone (POM ? LoDEX) in refractory or relapsed and refractory multiple myeloma. J Clin Oncol. 2014;32(suppl) (abstract TPS8625). 33. Dimopoulos MA, Palumbo A, Corradini P, et al. An updated analysis of the STRATUS trial (MM-010): safety and efficacy of pomalidomide plus low-dose dexamethasone (POM ? LoDEX) in patients (pts) with relapsed/refractory multiple myeloma (RRMM). Blood.
Patients Patients were followed in the French Reference Center for Lysosomal Diseases. A total of 35 type 1 GD patients were recruited prospectively between June 2012 and July 2015. Patients were considered anemic when the hemoglobin (Hb) levels were strictly below 11. 5 g/dL for children between 2 and 12 years old, 12 g/dL for women and 13 g/dL for men. No patient was splenectomised. In this cohort, GD was moderate and 10 patients exhibited anemia. Hemograms and biochemical data related to anemia for the 20 untreated GD patients who had never received ERT were compared according to their anemic status. For the in vitro erythropoiesis study, blood samples were collected from 24 GD patients, including 9 untreated patients and 15 patients treated with ERT. Detailed clinical and biological information is provided in Table  1.
GD erythroid progenitors exhibit decreased proliferative capacity Cell expansion and viability were measured during the two culture phases using trypan blue staining. The cell proliferation capacity is reported as the absolute number of viable cells at days 0 and 15 of culture. Our results showed a decrease of the proliferation capacity of 7. 55-fold in GD cells compared to those from the control (GD=121. 9 vs. control=920. 7-fold, P<0. 0001, Figure  4A ). This reduced proliferation resulted in a dramatically smaller absolute number of band 3 hi erythroblasts produced at the end of the differentiation (GD=0. 6x10 6 vs. control=14x10 6 , P=0. 0001, Figure  4B ), despite a higher percentage of differentiated cell population. Taken together, these data showed that acceleration of erythroid differentiation and maturation occurred to the detriment of cell proliferation and provided evidence for dyserythropoiesis in GD.
For each SNP bin (r 2 > 0. 5), SNP with the most significant evidence for association was included in the multivariate model. Multivariate analyses were done by stepwise conditional logistic regression (SAS v. 9. 3). Logistic regression was also used to estimate the odds ratio for each individual SNP in the T1R-affected subset. Briefly, the TDT evaluates the non-random transmission of alleles from heterozygote parents to affected offspring. We used the non-transmitted alleles from the TDT to create up to three unaffected pseudo-sibs per family, one for each possible genotype. We compared the original T1R-affected offspring with T1R-unaffected pseudo sibs in a matched case-control design as described in  [28]. Under the additive model, the TDT and the conditional logistic regression statistics result in the same P values.
Parkinson's disease and inflammatory bowel disease data Genotype associations of LRRK2 and PD were obtained from the PDgene database (www. pdgene. org). LRRK2 variants associated with PD were obtained from a GWAS meta-analysis of 14 studies with a total population sample of 12,771 PD cases and 93,386 controls  [32]. Genotype associations of LRRK2 variants with IBD and CD were obtained from the IBDgenetics database (www. ibdgenetics. org). The IBDgenetics population sample consisted of 42,950 IBD cases  (22, 575 CD and 20 ,417 UC patients) and 53,536 controls  [21, 22].
Acknowledgments We thank all leprosy patients and their family who participated in this study. We thank all  CLINT  ( Canadian LRRK2 in Inflammation Team ) researchers, the members of the  Schurr lab and the members of the laboratory for Human Genetics of Infectious Diseases in Paris and New York City  for useful discussions and suggestions on the work presented. CLINT Investigators include:  Earl Brown ,  Derrick Gibbings ,  Shawn Hayley ,  David Park ,  Dana C. Philpott ,  John D. Rioux , and  Michael Schlossmacher.
5-conjugated anti-DC-SIGN (DC-specific ICAM-3 grabbing-nonintegrin or CD209, member of the CLR family, specific marker of immature DCs), Alexa Fluor Ý 488-conjugated anti-MR (Mannose Receptor or CD206, member of the CLR family, specific marker of immature DCs and macrophages), and streptavidin APC-conjugated anti-TLR4 (biotin antibody, an LPS receptor with activation functions). Antibodies were obtained from BD Biosciences, except anti-MR (Biolegend). Corresponding murine isotypematched and non-labeled antibodies (BD Biosciences or Biolegend) were used as controls. The cells were analyzed by a BD-LSRII flow cytometer with FACSDiva Software (BD Biosciences) at the CICS. Fluorescence compensation adjustments were performed. Gates were set on living DCs based on their forward/side scatter (FSC/SSC) properties.
Flow Cytometric Analysis of Microbial Effects on DC Phenotype. During the immune response, bacterium internalization can then induce DC activation and maturation, resulting in modifications detectable by cytometry of numerous membrane markers and permitting to distinguish immature DCs from mature ones. In our study, DC activation and maturation were assessed by changes affecting an extensive phenotype of the cell membrane. As expected, immature DCs were characterized by low levels of CD86, HLA-DR, and CD14 expression (the latter was compared to its initial level in monocytes before IL-4 and GM-CSF treatment, data not shown), together with high levels of DC-SIGN and MR expression (Figures  2  and 3 ). Comparatively, LPS-induced DCs expressed a phenotype characteristic of fully mature DCs with increased levels of CD86 and HLA-DR (Figures  3(a  Incubation with low or medium doses of G.
Source of data This was a prospective observational cohort study using data from the Pharmacoepidemiologic General Research eXtension (PGRx) information system which is a set of population-based registries including case-patients (cases) with specific diseases recruited by their specialist physician and referent-patients (controls) routinely recruited by their general practitioner (GP). 14, 15 Inclusion and exclusion criteria are similar for cases and controls, except for the disease of interest. Medical information is collected by specialists (for cases) and GPs (for controls). All patients undergo the same standardized telephone interview to collect information on family medical history, lifestyle and use of medication.
Measures All patient data were collected through dedicated case report forms (CRFs), similar in cases and controls regarding socio-demographics, personal medical history and family history of autoimmune disorder (in first-degree relatives): multiple sclerosis, lupus erythematosus, rheumatoid arthritis, Crohn disease, chronic ulcerative colitis, Hashimoto thyroiditis or Graves-Basedow disease. In cases, data were also collected on the ITP at baseline and after 12 months of follow up (Online Supplementary Appendix). The time elapsing between diagnosis and outcome measure at 12 months was preferred, given that first symptoms are often more difficult to specify. Recovery and chronicity were defined as in Table  1.
Statistical analysis Statistical analysis was performed with SAS software version 9. 18 and all comparative tests were two-sided with a type-1 error set at α=0. 05. Bleeding symptoms were categorized into: a) no bleeding; b) cutaneous bleeding alone; and c) severe bleeding defined as mucocutaneous and/or visceral bleeding (epistaxis, or bleeding of the mucous membrane, or visceral bleeding). The titration of antinuclear antibodies (ANA) was considered positive if the titer was more than 1/80. Further details are provided in the Online Supplementary Appendix.