dataesr/scientific-paragraphs-categorization huggingface dataset:
As more and more resources are published on the World Wide Web, crosslinking between classifications and databases may facilitate their simultaneous use. Although care has been given to apply the inclusion criteria uniformly, there are disorders without proven molecular or biochemical defect for which inclusion in the Nosology as distinct entities seem somewhat arbitrary. For these disorders, discussion within the Nosology group, where individual opinions can be harmonized and, if needed, corrected by the collective expertise, is of great importance. Moreover, there are disorders listed in MIM that have not met our inclusion criteria, in most instances because of too few observations or because of the lack of features allowing clear diagnostic distinction from other disorders. It is likely that additional observations or the demonstration of a distinct molecular basis will allow for the inclusion of many of these disorders in the future, either as separate entities or as ''variants'' of already existing ones.
OMIM and the Nosology Because of the importance of consistency between parallel databases, the relationship between the Nosology and the OMIM database has been reviewed. The more comprehensive nature of the data collection and filing in MIM and the different nature of its revision process can lead to a divergence between the inclusion of nosologic entities and their denomination. Thus, MIM is in general more appositional, while the Nosology tries to do some ''housekeeping'' of entities by regrouping them and by eliminating those that have been incorporated into others. Efforts to made to harmonize the MIM and the Nosology are underway.
Outlook The increasing availability of massive parallel sequencing and other new sequencing technologies will likely result in a rapid identification of novel disease-causing genes, but also in novel phenotypes associated with mutations in genes already linked to other phenotypes. In the near future, the catalog of skeletal phenotypes with a genetic basis may become so large as to surpass the scope of a ''Nosology'' as we understand it presently, and the Nosology will transform into an annotated database. Even in that case, the many revisions of the Nosology will hopefully have paved the way by setting standards for the recognition and definition of skeletal phenotypes. Past versions of the Nosology have been translated in different languages and have found their way into textbooks of pediatrics and genetics.
Patients did not receive investigational product during years 4 and 5 of the study. Patients and investigators remained blinded until the end of the fifth year of the study. The study protocol (European Union Drug Regulating Authorities Clinical Trials (EudraCT) number 2006-003258-98) was reviewed and approved by local regulatory authorities and independent ethics committees in each country, and the study and year 5 extension were conducted according to the Declaration of Helsinki and Good Clinical Practice-International Conference on Harmonisation guidelines. Patients provided their written informed consent before the start of any study-associated procedure, and reconsented prior to participation in the year 5 extension.
If a patient took two or more rescue medications on the same day, the highest score was used for the RMS  [14]. Efficacy analyses were performed on the full analysis set (FAS). In contrast to other symptoms scores, no last observation carried forward data adjustment is carried out with the Average adjusted symptom score (AAdSS), thereby reducing the potential for skewing of the data. After the study had commenced, guidance from health authorities and professional societies regarding the primary efficacy endpoint of AIT clinical trials subsequently recommended the use of a score that considers both symptoms and rescue medication use, to avoid an underestimation of symptoms severity. In response to this guidance, the average adjusted symptom score (AAdSS)  [14]  was introduced as primary efficacy measure  [12, 13].
Study population Demographics and baseline characteristics for the FAS Year 4 have already been published  [13]. Data from FAS Year 5 were well-balanced and comparable across treatment groups (Table  1 ). Randomized patients in the FAS Year 5 had moderate-to-severe grass pollenassociated ARC, as denoted by a mean RRTSS of 14. 1 (SD: 1. 7), for a mean duration of 12. 8 years (SD: 9. 0). The majority (59. 4%) of patients were polysensitized to grass pollen and another allergen, and Global Initiative for Asthma (GINA) treatment Step I for asthma  [16]  was reported in 12. 7% of patients. Overall, 633 patients with ARC were randomized to receive placebo (n = 219) or 300IR 5-grass pollen tablet starting 4 months (4 M; n = 207) or 2 months (2 M; n = 207) before the estimated start of the grass pollen season (Figure  1 ).
Data variables Data variables were collected in relation to study objectives. For Objective 1, these included the number of machines and the number of Xpert tests conducted since installation, including successful tests with their results and unsuccessful tests with their reasons. For Objective 2, data variables included the number of tests performed for each Xpert machine. Given that a microscopist works 8 h per day, 20 days/month, the estimated maximum capacity for a 4-module machine is 400 tests/month (for the 16-module machine it is 1600 tests/month), excluding chances of error. The data sources for these two objectives were the archive files, retrieved and degenerated into raw data for analysis. For Objective 3, data variables included a score for each component on the standardised laboratory monitoring and supervision checklist.
Acknowledgments The authors thank  I. Alexandre ,  V. Ipotesi ,  N. Akdim ,  J. Raleche ,  L. Delagarde ,  A. Meloni ,  Professor A. Sapino ,  Dr. C. Westhoff ,  Dr. E. Dragoescu ,  Dr. I. Keller ,  Dr. SA Polyzos ,  Dr. T. Leger ,  MC Portenier ,  S. Chambris ,  P. Pausicles , the  BIUM, CMDP/APHP , and  NCA/Avicenne teams.
Methods We performed a prospective observational study. Every ICU included all death occurring during a month randomised in the year of the study. Demographic data were collected as well as circumstances of death (organ failure and organ support at this time). An organ failure was defined by a SOFA sub-score ≥ 3. Population of the study was dichotomised in expected death (following withholding or withdrawal of care, or brain death) and unexpected death (following maximal intensity of care). Data are expressed as median and IQR. Comparisons were made by a Mann-Whitney or chi-squared tests as appropriate. A p value < 0. 05 was considered as statistically significant.
The mutations are highly heterogeneous, with more than 400 different mutations already documented (http://www. leschnyhan. org/en/research/mutations-database/). Depending on the mutation, the enzyme exhibits none or residual enzymatic activity. Residual activity correlates with the severity of symptoms and in particular with the degree of neurological disturbances  [3, 11]. Hence, a phenotypic classification in three groups has now been accepted  [3, 4, 9]. Lesch-Nyhan Disease (LND) patients display neurological deficiencies and self-injurious behaviors; they usually have undetectable HGprt activity. A second set of patients with various degrees of neuromuscular symptoms but no self-injurious behavior were grouped in HND (HGprt-related Neurological Dysfunction), they typically have a residual HGprt activity in live fibroblast assay.
e. pairs where the patient marker level is higher than the control one, if the marker is expected to be increased in patients, and reciprocally if the marker is expected to be higher in controls. All computations were performed with the R statistical package v2. 5 (http://www. r-project. org/). For the ROC analyses, we used the R ROCR library  [20]. All tests were performed using a bilateral formulation. P-values less than 5% were considered as statistically significant. All metabolic distributions and ROC curves were drawn using Graph-Pad Prism software.
Genotype/Phenotype classification of full LND and LN Variants The French cohort of Lesch-Nyhan patients was split into the three approved sub-groups  [3]  depending on the degree of neurological disturbances, from none to severe: HRH, HND, LND. It should be stressed that the average diagnosis age of the patient of the 3 groups varies significantly due to the obviousness of the most severe symptoms (Figure  2A ). Sequencing analysis of the HPRT1 gene revealed 61 different mutations among these 85 patients, spanning 65 families, 27 of which were novel. Of note, all these mutations including the 27 newly identified are listed in http://www. lesch-nyhan. org/en/research/mutations-database/. While the nature of the mutations was clearly not evenly distributed in the three groups (Figure  2B ), we found that the location of the mutation was not a good prognostic marker of the severity of the disease (Figure  2C ).
21 he prospective, observational Arthritis, Rheumatism, and Aging Medical Information System database study evaluated the GI toxicity of ibuprofen, aspirin, and acetaminophen at various doses in patients with RA (n=5,692) or OA (n=3,124) and found no GI toxicity rates of 1% when each respective agent was taken alone, especially when used occasionally or intermittently at lower doses. 22 Interestingly, the investigators found that rates of GI events were significantly higher (P0. 05) in the acetaminophen group taking concurrent therapy plus corticosteroids compared with those taking either ibuprofen or aspirin with concurrent therapy plus corticosteroids. 22 n comparisons of GI AEs among NSAID users, results from several meta-analyses further support a lower risk of GI AEs with ibuprofen compared with other NSAIDs.
Selective serotonin reuptake inhibitors and tricyclic antidepressants ] [96]  Coadministration of NSAIDs in patients taking SSRIs can substantially increase the risk of bleeding. 97, 98 A Dutch population-based cohort study (N=1,961) found that patients prescribed SSRIs plus NSAIDs were prescribed ten times more peptic ulcer drugs (proxy for GI events) than patients receiving an SSRI alone (incidence rate ratios: 12. 4; 95% CI: 3. 2-48. 0 vs 1. 2; 95% CI: 0. 5-2. 8, respectively). 98 In a case-control study utilizing a UK general practice research database to identify cases of upper GI bleeding (n=1,651) or ulcer perforation (n=248) and age/sex/time-matched controls (n=10,000), concurrent use of NSAIDs and SSRIs had a more than multiplicative effect on risk of bleeding. Compared with nonuse of both drug classes, RR (95% CI) for bleeding was 2.
Lithium Several prescription-strength NSAIDs have been associated with substantial DDIs resulting in ADRs when coadministered with lithium. One study assessed reports of DDIs between lithium and selective COX-2 inhibitors as reported in the FDA's Adverse Event Reporting System database as of January 2003. 102 Thirteen cases of increased lithium concentration were reported with rofecoxib (plasma concentration increased by 58%-448%), and five were reported with celecoxib (plasma concentration increased by 56%-99%). Increased lithium concentrations were associated with clinical AEs including tremor, nausea/vomiting, upset stomach, renal insufficiency, weakness, ataxia, increased muscle tone, dysarthria, slurred speech, lethargy, sedation, disorientation, nystagmus, and flu-like symptoms. 102 he DDI mechanism is unclear; however, NSAID-mediated inhibition of renal prostaglandins may decrease renal lithium excretion.
Measures were implemented to ensure data quality: onsite monitoring visits of 100% of the data in 5% of centres selected at random over 5 years of follow-up; regular telephone contact with investigators; and centralized verification of the eCRF for completeness, consistency, and accuracy. Data were collected on patient baseline characteristics, risk factors and lifestyle, medical history, physical condition and vital signs, symptoms, and treatments. We analysed the CLARIFY population by antithrombotic therapy (OAC alone or combined with antiplatelet therapy, and one or more antiplatelet[s] without OAC). CLARIFY is an observational registry, and the size of the population is not based on treatment comparison; the number of patients in this analysis was dependent on the presence or absence of atrial fibrillation in a cohort of patients with stable CAD.
Statistical Analysis All CLARIFY data are collected and analysed at an independent academic statistics centre, the Robertson Centre for Biostatistics, University of Glasgow, UK. Baseline variables are summarized as means (standard deviation) or medians (interquartile range) for continuous data and as counts and percentages for categorical data, and were based on patients in whom data were available. Comparisons between patients with OAC use and those without were made using one-way ANOVA or the Kruskal-Wallis test for continuous variables and Pearson's Chisquared test or Fisher's exact test for categorical variables. A multivariable analysis of independent correlates of OAC use was performed using a logistic regression model. All clinical baseline variables, with the exception of HAS-BLED score, were considered for entry into the model as predictors of OAC use and univariate models for each were produced.
The multivariable model was built using a stepwise selection method applied to the remaining significant univariate predictors. A sensitivity analysis on the multivariable model excluding patients from East Asia was also performed to determine whether clinical differences in guidelines for this population affected the multivariable model. All analyses were performed using SAS version 9. 2. A significance level of 0. 05 was used to test for statistical differences; all tests used were two-sided.
Discussion In this contemporary international cohort of patients with stable CAD and AF, most of whom are theoretical candidates for anticoagulation, less than 50% of patients received OACs. Half of the patients received antiplatelet therapy alone and one-fifth received antiplatelets plus OAC. This analysis is the first of its kind to evaluate the applicability of the AF guidelines in this subgroup of patients with stable CAD and, to our knowledge, is the largest published dataset in this population, in whom antithrombotic management strategies have been related to baseline clinical characteristics  [7]. Limited published evidence is available on the optimal management strategy for patients with CAD and AF  [8] [9] [10] [11] [12] [13]. Our population reflects a "real-world" scenario for the applicability of current AF guidelines.
In our analysis, most of the patients had a CHA 2 DS 2 -VASc score 2, with only a minority receiving guideline-recommended antithrombotic therapy. These data suggest under-treatment, but also possible over-treatment, with 21. 5% receiving both OAC and antiplatelet therapy, although whether there is benefit or harm in adding antiplatelet therapy to OAC in patients with both AF and coronary artery disease remains debatable  [14]. We identified risk factors associated with lack of OAC use. Compared with previous studies on guideline adherence in the more general setting of AF, and based on the 2010 guidelines  [1] , we found that an even lower percentage of patients with stable CAD and AF was appropriately treated  [15, 16]. When divided into groups at increasing risk with higher CHA 2 DS 2 -VASc score, patients most at risk of thromboembolism were poorly treated with more OAC.
Of note, East Asia had guidelines with slightly different thresholds and INR target for OAC use whilst the region contributed substantially to the overall population. Removing East Asia and running a stepwise selection model on this population as a sensitivity analysis provided results that were similar (data not shown). In a consensus document on the optimal management of antithrombotic therapy in AF patients undergoing PCI/stenting, various antithrombotic strategies have been offered according to the haemorrhagic risk and the clinical setting (elective or acute)  [22]. At discharge from hospital, triple antithrombotic therapy (oral anticoagulation, aspirin, and clopidogrel) is recommended, ranging from 2 weeks for elective procedures with high haemorrhagic risk up to 6 months for acute coronary syndrome procedures when the bleeding risk is low or intermediate.
Methods Patients charts of 16 patients undergoing 20 MRIs with TPTD-catheters were analyzed for side effects. To detect potential catheter dysfunction we compared the last measurements before and after MRI (Wilcoxon-test for paired samples; IBM SPSS 22). Furthermore, a questionnaire regarding the local standard procedure in case of MRI in patients with PiCCO-catheter was sent to 11 experts in hemodynamic monitoring.
Diagnostic criteria for potential FH The prevalence of FH was estimated using a modified version of criteria used in the MedPed/WHO algorithm  [7]  and by the DLCN  [8] ; 2 points were given if the age at the index event was <55/60 years for men/women OR if self-reported age of first diagnosis of CHD was <55/60 years for men/women; 1 point was given for a positive family history of premature (<55/65 years for men/ women) CVD. The presence of arcus cornealis or tendon xanthomata was not recorded in the EUROASPIRE IV survey. A large majority of the patients (85. 7%) was on statin therapy at the moment of blood sampling. To estimate the "untreated" LDL-C plasma level in these patients, information on the current intake of statins was collected. Participants were asked to bring all the drugs that they were taking on a daily basis to the interview and the interviewer collected the data regarding the dose; in case the interview was done at the home of the patients, detailed information was also collected as to the type of statin and the dosage.
Statistical methods Prevalences were given as percentages. Gender-and center-specific prevalences of potential FH were age-standardized according to the direct method using the total sample as reference. Groups of patients with and without potential FH were statistically compared according to multilevel logistic modelling. These hierarchical models accounted for the clustering of patients within centres. In addition, P-values were adjusted for potential confounding due to differences in distributions of gender and age at interview. A level of <0. 05 was a priori chosen to indicate statistical significance. All analyses were performed by means of SAS statistical software release 9. 1 (SAS Institute Inc. , Cary, North Carolina, USA).
Discussion Among the coronary patients of the EUROASPIRE IV survey the prevalence of potential FH was calculated at 8. 3% or 1 in 12. The prevalence of FH in selected series in the literature varies from 1 in 200 to 1 in 2000 [12e14]. In the Danish general population it was 1 in 200 according to the DLCN criteria  [15]. In the US population the prevalence of potential FH according to an adapted version of the DLCN criteria in the NHANES 1999e2012 data was 0. 23% or 1 in 427  [16]. In a Chinese community, aged 20 yrs and above the prevalence of probable and definite FH according to modified DLCN criteria was 0. 28% or 1 in 357  [17]. Among patients with established CHD however, the prevalence of potential FH is not clear. In a series of consecutive patients aged <60 years admitted with an acute myocardial infarction to hospitals in the Yorkshire region in 1995 and in whom cholesterol had been measured (n ¼ 292), 36 cases of FH (12.
Quantitative measure of cavities area In order to obtain comparable images between the RTVue-100 and the Spectralis, a TIFF image centered on the fovea corresponding to 3. 6 x 3. 6 mm was extracted from the en face scans obtained with the two devices. These en face OCT scans were analyzed using Image J software (Version 1. 48q, Wayne Rasband, National Institutes of Health, Bethesda, MD, USA). Briefly, after conversion to 8-bit grayscale images, hyporeflective spaces were identified via the built-in "Adjust threshold" function (with grayscale intensity threshold set to 64). On the resulting binary images, all identified hyporeflective spaces were transformed to white areas on a black background. A list of surfaces was obtained using the base package particle analysis function. In order to reduce noise, surfaces greater than 0.
001 mm 2 was set as the threshold for inclusion in particle analysis calculations. Two statistical analyses were then performed. First, the distributions of cavities areas in the inner nuclear layer and in the complex of the outer plexiform and Henle's fiber layers were compared within each subject using a Mann-Whitney-Wilcoxon sum-rank test for non-normal distributions. Second, overall comparison of cavity areas between the inner nuclear layer and the complex of the outer plexiform and Henle's fiber layers was performed by a Kruskal-Wallis test and a multiple comparison post-test. Statistical analyses were performed on R Software (Version 3. 1. 1, R Foundation for Statistical Computing, R Core Team, 2014, Vienna, Austria. http://www. Rproject. org/) using the "ggplot2" package (H. Wickham.
ACKNOWLEDGEMENTS A. Funding/Support: none B. Financial disclosures: Matet: meeting expenses ( Laboratoires Alcon S. A. S. , Rueil-Malmaison, France; Laboratoires Théa, Clermont-Ferrand, France )  Savastano: no financial disclosures Rispoli: no financial disclosures Bergin: no financial disclosures Moulin: no financial disclosures Lassiaz: no financial disclosures Behar-Cohen : no financial disclosures Lumbroso: consultant (Optovue, Fremont, CA) C. Author contribution: -Design (BL, FBC) and conduct of the study (PC,  MCS, MR, AMa, AMo, CB) -Collection of data (MCS, MR, BL, AMo, PC, FBC, AMa, CB) -Management (MR, MCS, AMo ), analysis (AMa, CB), and interpretation (BL, FBC, PC) of the data -Preparation (AMa, MCS, CB), review (PC, FBC, BL) and approval of the manuscript (AMa, MCS, MR,  CB, AMo, PC, FBC, BL) Each  author meets the 4 criteria set by the  International Committee of Medical Journal Editors (ICMJE)  required to claim authorship.
Clinical investigation and molecular analyses The clinical evaluation was performed at the Department of Medical Genetics, Hospital Erasme, Brussels, Belgium, and the Institut de Pathologie et de Génétique, Gosselies, Belgium, and research was performed following a protocol approved by the University of Ulm Ethics Committee. After obtaining written informed consent for participation in the study, including consent to report individual patient data, we sequenced the coding exons and splice sites of GDF5 (NM_000557. 2) and BMPR1B (NM_001256794. 1) on genomic DNA after PCR amplification. Primer sequences are available on request. PCR products were sequenced on an ABI 3730 DNA Analyzer with BigDye chemistry v3. 1 (Applied Biosystems). Sequence traces were assembled, aligned, and analyzed with the Seqman software (DNASTAR Lasergene).
The BMPR1B intragenic short tandem repeat (STR) markers D4S2278 and BMPR1B-STR2 (forward primer 5'-TTAAAAGTAAAGACCATATAAAGG-3'; reverse primer 5'-GGACTTAAAACTCTGCAACAAC-3') were genotyped after PCR amplification on an ABI 3730 DNA Analyzer. Single nucleotide polymorphism (SNP) array genotyping was performed using a Genome-Wide Human SNP Array 6. 0 (Affymetrix), according to the manufacturer´s instructions. Linkage analysis and haplotype reconstruction were performed using the program ALLEGRO  [10]. Haplotypes were presented graphically with HaploPainter  [11]. All data handling was performed using the graphical user interface ALOHOMORA  [12].
Structural analysis The BMPR1B substitutions Arg31Cys (identified here) and Arg31His (present at low frequency in public databases; rs200035802) were modeled on the basis of the crystal structure of the human BMPR1B extracellular domain bound to human GDF5 (PDB entry 3EVS,  [13] ). The side chain of Arg31 was exchanged for either a cysteine or histidine using the ProteinDesign tool of the software Quanta2008 (MSI Accelrys) and rotamer searches were performed to identify the most likely side chain conformation. Potential alternative disulfide connectivities were analyzed by performing energy minimization runs in vacuo employing only geometrical energy terms.