dataesr/scientific-paragraphs-categorization huggingface dataset:
Study Population Among the 184 patients admitted to ICUs with suspected COVID-19, 73 were excluded: 14 because of non-confirmed diagnosis and 59 because of missing data (Figure  1 ). One hundred and eleven patients (75 males, 68%) with a median age of 67 (58-75) years were then included in the study. As shown in Table  1 , the median Charlson Index was 3 (2-5) and most of the patients (48%) had at least two comorbid conditions such as hypertension (47%), diabetes (31%), chronic heart diseases (20%), chronic pulmonary disease (20%), or chronic kidney disease (13%). At ICU admission, the median SAPS II was 37. The severity of patients' illnesses was mainly related to respiratory failure, given that the median PaO 2 /FiO 2 ratio at admission was 140 (98-154) and severe acute respiratory distress syndrome (ARDS) according to the Berlin definition occurred in almost one third of the patients (31%).
Institutional Review Board Statement: This study was conducted according to the guidelines of the  Declaration of Helsinki , and approved by the  Institutional Review Board of Montpellier University Hospital  (IRB-MTP_2020_11_202000644, accessed on 16 November 2020). This study was also registered at ClinicalTrials. gov( NCT04641988 ), accessed on 23 November 2020). The  Institutional Review Board of Montpellier University Hospital  waived the need for signed consent to participate, according to the French laws.
What did the study ask? This ongoing open-label extension study collected long-term data on adverse events (AEs) and vital status of PAH patients treated with selexipag. What were the study outcomes/conclusions? Over the 7-year follow-up period, the median (min, max) exposure to selexipag in the study population (n = 953) was 31. 7 months (0, 106), corresponding to a total of 3054. 4 patient-years. The most frequently reported AEs were related to known prostacyclin-related effects and/or underlying disease. Kaplan-Meier survival estimates at 1, 3, 5 and 7 years in the population of patients randomised to selexipag in GRIPHON (n = 574) were 92. 0%, 79. 3%, 71. 2% and 63. 0%, respectively.
Study Design GRIPHON (NCT01106014) was a global, multicentre, double-blind, randomised, placebocontrolled event-driven phase 3 study, which assessed the safety and efficacy of selexipag in patients with PAH  [4]. Briefly, selexipag/placebo were titrated over 12 weeks to an individualised dose of 200-1600 lg twice daily (b. i. d), based on tolerability. Patients received double-blind treatment until they experienced a morbidity/mortality (primary endpoint) event, discontinued prematurely, or until the end of the study (reached when 331 primary endpoint events had occurred). Primary endpoint events included disease progression or worsening of PAH that resulted in hospitalisation, initiation of parenteral prostanoid therapy or long-term oxygen therapy, need for lung transplantation or balloon atrial septostomy, or death from any cause.
Disease progression was defined as a decrease from baseline of at least 15% in the 6-min walk distance (6MWD) accompanied by a worsening in WHO functional class (FC) (for the patients with WHO FC II or III at baseline) or the need for additional treatment of PAH (for the patients with WHO FC III or IV at baseline). All events were adjudicated by a blinded independent critical-event committee  [4]. GRIPHON OL (  NCT01112306 ) is an openlabel, multicentre study to assess the long-term safety and tolerability of selexipag in patients with PAH (Supplementary Fig. 1 ). Patients enrolled in GRIPHON could enter the GRI-PHON OL study either after experiencing a morbidity event during double-blind treatment or at the end of the study if they were still receiving study treatment. The dose at which selexipag was started in GRIPHON OL depended on the reason to enter the OL and/or the treatment allocation in GRI-PHON.
Statistical Analyses All analyses were performed using data from both GRIPHON and GRIPHON OL up to a cutoff date of 1 September 2019 and were descriptive in nature. For the analyses of safety and tolerability, all patients treated with at least one dose of selexipag in GRIPHON or GRIPHON OL were included, defined as the safety/tolerability set. For the post hoc analyses of long-term survival, all patients randomised to selexipag in GRIPHON were included, defined as the survival analysis set. The Kaplan-Meier (KM) method was used to estimate time from selexipag initiation to death. This analysis included deaths that occurred more than 30 days after end of treatment, if reported to the study sponsor. Analyses were performed on all patients, as well as on subsets of patients grouped according to REVEAL 2.
Data Availability. The datasets generated during and/or analysed during the current study are available; requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site http://yoda. yale. edu. Open Access. This article is licensed under a Creative Commons Attribution-NonCommercial 4. 0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material.
ACKNOWLEDGEMENTS We thank the participants of the study. Funding. Funding for the study and for the journal 's rapid service and open access fees was provided by  Actelion Pharmaceuticals, Ltd , a  Janssen Pharmaceutical Company of Johnson & Johnson. Medical Writing and/or Editorial Assistance. Medical writing support was provided by  Jatta Huotari  and  Laura Corbett  of eluSCIdate ltd (Meggen, Switzerland) and was funded by  Actelion Pharmaceuticals, Ltd , a  Janssen Pharmaceutical Company of Johnson & Johnson. Authorship. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published. Author Contributions.
1] [112] [113]  The IL-5 pathway seems to be important in symptom development, but sustained untargeted parallel stimuli may explain such recrudescence after discontinuation. In CRSwNP, a phase III study (SYNAPSE) recently demonstrated that mepolizumab significantly improved the total nasal polyp score and nasal obstruction in comparison with placebo. 114 A randomized clinical trial to assess the efficacy and safety of benralizumab in eosinophilic CRSwNP is ongoing (NCT04157335). In contrast, mepolizumab failed to demonstrate significant clinical effects on AD at 2 weeks in a small RCT. 115 Benralizumab phase 2 clinical trials are recruiting patients with moderate to severe AD (NCT04605094, NCT03563066). The results from such trials would help define the relevance of targeting eosinophils in AD.
In most severe cases with weak therapeutic response, dupilumab cessation is needed. Until now, to our knowledge, the underlying immune mechanisms remains poorly understood. 4] [125]  Strategies to find suitable biomarkers (blood eosinophils, FeNO, serum periostin) to select potential responders were designed but did not succeed. 126 In contrast, phase 3 clinical trials recently demonstrated a significant improvement of AD under treatment with tralokinumab with or without topical steroids compared with topical steroids alone or placebo. 127, 128 Promising results from a phase II study considering lebrikizumab in moderate-to-severe AD led to the recent onset of 2 parallel phase III clinical trials (ADVOCATE 1 and 2, NCT04146363, NCT04178967). 129 These different response profiles highlight that despite common pathophysiological pathways, it is still difficult to predict how individual responses occur both between type 2 inflammatory diseases and within a specific disease.
Beyond canonical type 2 cytokines, promising new targets have been discovered. Chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTh2) is activated by prostaglandin 2, promoting the chemotaxis and activation of Th2 lymphocytes and eosinophils. In a proof-of-concept study, AZD1981, an oral CRTh2 antagonist, failed to show a significant increase in peak expiratory flow (primary endpoint), but trends towards an improvement in asthma control score were seen in moderate-to-severe asthma patients. 130 Other data from atopic asthmatic patients display a trend towards an increase in FEV1 under treatment. 131 In parallel, fevipiprant, another oral CRTh2 antagonist, failed to achieve a significant improvement in severe asthma considering the rate of exacerbation. 132 Comparable failure was observed considering the targeting of CRTH2 in AD (NCT01785602).
In parallel, an antibody targeting IL-33, REGN3500, is currently being tested in AD and asthma as monotherapy or in combination with dupilumab (NCT03736967, NCT03112577, NCT03736967). Moreover, astegolimab, a monoclonal antibody targeting IL-33 receptor ST2, recently demonstrated in a phase 2b clinical trial a reduction of annualized asthma exacerbation rate in treated severe asthmatics compared to placebo. 137 Nevertheless, to our knowledge, no anti-IL-25 antibodies are currently being tested in clinical trials. The results from biotherapies targeting alarmins are awaited to evaluate the efficiency of stopping epithelial upstream signals to prevent type 2 immunity sustainment.
Biotherapies of clinical trials in type 2-driven airways and cutaneous diseases Ref 97,98,101,102 103,104,114,115 106-108 105 116-119 124-125-128 123 132 130 136 Asthma Improved symptoms Improved symptomsReduction of OCS Improved symptomsReduction of OCS Improved symptoms Improved symptomsReduction of OCS No effect No effect No effect No effect Improved symptoms No data available CRSwNP Improved symptoms Reduced need for surgery OngoingNCT04157335 Withdrawn Improved symptomsReduced need for surgeryReduction of OCS No data available OngoingNCT04146363NCT04178967 No data available No data available No data available OngoingCombination with dupilumabNCT03112577 AD No effect No effect OngoingNCT03563066NCT04605094 No data available Improved symptoms Improved symptoms OngoingNCT04146363NCT04178967 No effectNCT01785602 No data available No data available Ongoing Phase IINCT03736967 Targeted therapy Omalizumab Mepolizumab Benralizumab Reslizumab Dupilumab Tralokinumab Lebrikizumab Fevipiprant AZD1981 Tezepelumab REGN3500 Type 2-related pathway IgE IL-5 IL-4/Il-13 IL-13 CRTh2 TSLP IL-33 [103][104][105][106][107][108][109]Such treatments remain efficient in the long term (1 year and beyond), but some data are in favour of a loss of effect after discontinuation, for TA B L E 2 NA Abbreviations: AD, atopic dermatitis; CRSwNP, chronic rhinosinusitis with nasal polyposis; IgE, Immunoglobulin E, IL, Interleukin; OCS, oral corticosteroids.
Having a common set of tissues will facilitate the transfer of knowledge within and between species and will contribute to decrease animal experimentation. Combining data on the same samples will facilitate data integration. Quality control was performed on some tissues with RNA extraction and RNA quality control. More than 5,000 samples have been stored with unique identifiers, and more than 4,000 were uploaded onto the Biosamples database, provided that standard ontologies were available to describe the sample. Many tissues have already been used to implement FAANG assays, with published results.
Transcriptome Studies The FRAGENCODE project aimed at improving the genomic annotation of four species (cattle, goat, chicken, and pig). This was achieved by performing molecular assays on tissue dissociated cells (liver) and on sorted primary cells (CD4 + and CD8 + T lymphocytes) from two males and two females of each species. These assays included RNA-seq, ATAC-seq, and Hi-C to characterize the transcriptome, the chromatin accessibility, and the genome 3D topology in these cells, respectively  (Foissac et al. , 2019). Additional work was carried out using these RNA-seq datasets for the annotation of long-non-coding RNAs (lnRNAs)  (Jehl et al. , 2020). The collection is being used to complete the reference transcriptome of six tissues (cerebellum, lung, kidney, dorsal skin, skeletal muscle, small intestine/Ileum), in addition to the liver datasets reported by  Jehl et al.
CONCLUSION The FAANG tissue collection set up by INRAE and UCD illustrates the concept of biobank for research in genomics of domestic animals. Whereas the Biosamples database sets the reference identification for biological samples that can be used for research and makes possible to connect molecular data with these samples, additional procedures set up by a biobank are needed to manage the conservation and distribution of samples to the scientific community. To facilitate sample sharing, documenting sampling protocols as well as animal physiological status and raising conditions is needed and has been described in this protocol article. Combining different methods or types of analyses on a limited set of reference animals avoids the random noise due to variation among experiments and makes proposing a reference data set for genome structure and function possible.
FUNDING This work received funding for tissue collection and storage from the  CRB-Anim infrastructure  project,  ANR-11-INBS-0003 , funded by the  French National Research Agency  in the frame of the " Investing for the Future" program. The  FR - AgEncode  project was funded by the  SELGEN program  of  INRAE. The  FarmENCODE  project was supported by  United States Department of Agriculture, National Institute of Food and Agriculture  ( Competitive Grant  Project No. 2015-67015-22940  to HZ). Further support was provided by  United States Department of Agriculture, National Institute of Food and Agriculture, National Animal Genome Research Program, U. S. Poultry, Cattle , and  Swine Genome Coordination Fund, National Pork Board , and  Aviagen Ltd.
Data sources and case definition Since 1980, the cancer registry has collected data of every patient diagnosed with cancer whose registered residence was in the canton of Zurich at the time of diagnosis. The canton of Zug joined the registry in 2011, and the cantons of Schaffhausen and Schwyz joined in 2020. The cancer registry receives notifications from pathology and haematology laboratories, hospitals, and physicians, as well as death certificates from the Swiss Federal Statistical Office. Data include personal information and tumour characteristics, which are entered into the database by registry personnel. Tumours are coded by physicians and other appropriately trained personnel. Data completeness is annually monitored by calculating the percentage of cancers diagnosed by death certificate only (DCO) and the percentage of cancer that are morphologically verified  [18].
An increasing incidence rate together with decreasing mortality serves as indirect evidence of thyroid cancer being overdiagnosed. It appears that many indolent thyroid cancers are increasingly diagnosed, especially papillary microcarcinomas, which, if undetected, would probably not have led to symptoms. It is debatable if the small decrease in mortality justifies the high increase in incidence, which leads to psychological consequences, overtreatment and life-long substitution therapy. Therefore, targeted diagnostic strategies are necessary to avoid overdiagnosis of thyroid cancer. Our study had several strengths. We analysed populationbased, high-quality data from the cancer registry of the canton of Zurich, including all thyroid cancer cases by subtype during a 37-year period from all individuals living in the canton of Zurich.
Exon enrichment was performed using Agilent SureSelect Human All Exon V4. Paired-end sequencing was performed on the Illumina HiSeq2000 platform with an average sequencing coverage of 50× as described elsewhere  (10, 11). Details of the exome sequencing procedures are listed in the supplementary materials (see section on supplementary materials given at the end of this article) and potentially pathogenic variants were verified by Sanger sequencing (Supplementary Data 1). The samples were analyzed as trios.
Case 4 The proband was first seen in our clinic at the age of 12 days due to atypical genitalia. He was born to unrelated parents after in vitro fertilization twin pregnancy. Prenatal ultrasound demonstrated a female fetus. In addition, he had a subaortic membrane and atrial septal defect. No other anomalies were found. His karyotype was 46,XY. A hormonal evaluation indicated normal gonadotropin and testosterone levels. Sequencing of the SRD5A2, AR, and WT1 genes did not reveal pathogenic variants. WES revealed a de novo missense variant of BMP4 predicted as pathogenic. This variant is absent from all public singlenucleotide polymorphism databases. At the age of 12. 6 years, he had pubertal stage Tanner P3, penile length of 3. 5 cm and testicular volume of 4 mL.
However, these panels cover only genes that are known to be involved in sex development and determination. In contrast, WES theoretically sequences all genes in the human genome and as new genes causing DSD are discovered, the patient datasets can be reanalyzed for pathogenic variants that were not previously recognized. Since WES generates a wealth of genetic data, it has been recommended that the molecular results, together with the clinical and hormonal findings, be interpreted by a multidisciplinary team that includes clinicians and medical geneticists (5). Here, using WES, we identified seven causative variants (four novel and three previously reported) that explained the etiology of DSD. A de novo missense variant, c. 209G>T, p. R70L, in the BMP4 gene was identified in case 4, an 11.
Introduction Conformance assessment of manufactured parts to design tolerance specification is a major activity in the quality control process. Traceable ultra-high precision coordinate measuring machines (CMMs) to the SI metre definition are usually deployed to generate a set of data points lying on the artefact's surface  [1]. The recorded data will be processed in order to infer information about the measured surface. This task becomes difficult when it comes to the measurement of aspherical and freeform surfaces due to their complex geometry. Different factors could greatly affect the machine uncertainty, namely, the work piece, the hardware of the CMMs, the sampling strategy, the fitting algorithms, etc. [1] [2] [3]. Fitting could be defined as the process of determining parameters of the geometric features that best describe the measured data according to a defined criterion.
Key characteristics of reference fitting algorithms were outlined in  [8]. Thus, it is stated that they must: • perform well for representative data • work sensibly for unrepresentative data and be able to detect extreme cases • perform efficiently in poor cases Despite its importance, performance in terms of execution time is not the first characteristic sought for reference MZ fitting algorithms. However, as reported in  [2]  the algorithm must be stable and robust. The stability means that the underlying numerical operations are numerically stable. For example, small perturbations in input data must only result in small perturbations in output. Robustness refers to the algorithm ability to handle extreme cases. To establish the traceability chain for datasets analysis with a small uncertainty (below the nanometre level), the validation of implemented reference MZ fitting algorithms becomes indispensable in order to make sure that the returned values are correct.
H = 5 ∑ i=1 (-1) α i λ * i ∇ 2 d i (17) If this condition is not satisfied, then go to step 1. Otherwise, calculate contacting points coordinates by setting P * i = Q * i + (-1) α i en i (i=6,. ,N). Step 7: generate additional random points {P i } i=6,. ,N such that P i = Q i + θ i n i with {θ i } i=6,. ,N is a set of randomly selected numbers in the domain [-e, e]. It is worth mentioning that the proposed robust reference softgauges algorithm could work on all complex surfaces, as the only required knowledge is the normal vector with respect to the X-, Y-and Z-axis. Furthermore, the developed approach could be applied to continuous nominal shape described by a mathematical model or to discrete high accurate measured dataset.
Three configurations are selected, as given in Table  1. For each configuration, a dataset with predefined number of points  = {10,404, 50,024, 100,489} and  = 10 mm are generated to evaluate the performance of the two implemented MZ fitting algorithms (HTR and EPF). Three configurations are selected, as given in Table  1. For each configuration, a dataset with predefined number of points N = {10,404, 50,024, 100,489} and MZ re f = 10 -4 mm are generated to evaluate the performance of the two implemented MZ fitting algorithms (HTR and EPF). The corresponding PV values respectively PV EPF (or MZ EPF ) and PV HTR (or MZ HTR ), as well as execution time, respectively T EPF and T HTR , are compared with respect to the methodology presented in Figure  10. Initial data is rotated by angle π/20 around X-axis and π/15 around Y-axis, as well as translated by -1 mm in X-axis, 1 mm in Y-axis and -1 mm in Z-axis.
Difficulty Degree and Performance Measure Measuring an algorithm quality could be established by setting a framework, including:  (1)  the preconditions for quality measurement, (2) the analysis strategy of the meaningfulness of quality measures, as well as (3) the interpretation and use of the measured values  [31]. The degree of difficulty was discussed by Cox and Harris in  [32]. It aims at defining a quantity associated to each dataset that indicates at which level the generated reference softgauges challenge the algorithm under test. Thus, the methodology of testing metrology MZ fitting algorithms consists of generating datasets with increasing difficulty number. The output of the algorithm under test is assessed using a performance measure on each set. Therefore, the degree of difficulty could be sought as the difficulty to converge to a global optimum.
Conclusions In this paper, the generation of reference softgauges dedicated to the assessment of MZ fitting algorithms of complex shapes is provided. The developed robust approach is based on satisfying KKT first and second order optimality conditions before inferring reference softgauges with non-vertex solutions. It could be applied to continuous nominal shape described by a mathematical model or to discrete high accurate measured dataset. The implemented approach based on a non-vertex solution was adopted and investigated for the case of aspherical shapes. Nine reference softgauges were generated with predefined number of points and MZ re f = 10 -4 mm. The reference softgauges were submitted to two implemented MZ fitting algorithms (HTR and EPF). Results show the conformance of the returned values of MZ HTR and MZ EPF with the reference measurand ones MZ re f.
Case study The data used in this case study were obtained from experimental measurements conducted using strain gauges, which were installed on the runner blade of a Francis hydroelectric turbine of a power plant in Quebec (Canada). The measured locations on the blade are close to critical locations where the highest stress levels are found. For the purpose of this paper, the experimental uncertainties (ambiance error, human error, error of installation, etc. ) are ignored. The interpolation is performed between different steady-operating conditions of the turbine. Transient operating conditions, such as start-ups or stops, are not considered in this research because their specific dynamic behaviours do not correlate with steady-operating conditions. A steady-operating condition is  approximately defined as a regime of the turbine under which the guide vane opening, power and turbine head can be considered as quasi constant.