dataesr/scientific-paragraphs-categorization huggingface dataset:
Receiver oprating curve (ROC) analysis was performed. Results: Median serum levels of MRP8/14 in JIA patients, and both in oligo-and poly-JIA were significantly higher compared to healthy controls. Median serum levels of MRP8/14 were significantly higher in active and lower in inactive JIA patients compared to healthy 1 Pediatrics Department, Vasyl Karazin Kharkiv National University, Kharkiv, Ukraine Presenting author: Emediong S. Asuka Pediatric Rheumatology 2017, 15(Suppl 1):P84 This abstract is not included here as it has already been published. 2. To illustrate the radiographic appearance of JIA patients from head to toe, highlighting the differences between active and chronic disease. 3. To review the MR protocol and imaging techniques to study patients with JIA. Methods: We retrospectively review all available hospital medical records, including Electronic Patient Chart (EPC) and clinical database of our patients with diagnosis of JIA.
Background Infections are associated with biological therapies in psoriasis. Objectives To summarize the incidence of infections in patients with moderate-tosevere psoriasis treated with ixekizumab, an anti-interleukin-17A monoclonal antibody. Methods Infections are summarized from an integrated database of seven controlled and uncontrolled ixekizumab psoriasis trials. Data are presented from placebo-controlled induction (weeks 0-12; UNCOVER-1, UNCOVER-2 and UNCOVER-3) and maintenance periods (weeks 12-60; UNCOVER-1 and UNCOVER-2), and all patients exposed to ixekizumab pooled from all seven trials. Comparisons with etanercept were made during the induction period of two trials (UNCOVER-2 and UNCOVER-3). Incidence and exposure-adjusted incidence rates (IRs) per 100 patient-years (PYs) are reported.
• The overall safety of ixekizumab has been previously reported; this paper endeav- ours to provide more specific information about infections. What does this study add? • We report the incidence of specific treatment-emergent infections reported in a database of > 4000 patients with moderate-to-severe psoriasis treated with ixekizumab. • This study provides detailed accounts of infection-related adverse events categorized by special topics, including tuberculosis, Candida infections, staphylococcal infections, herpes zoster, viral hepatitis and infections preceded/accompanied by neutropenia. • We performed sensitivity analyses of infection rates over time for all patients trea- ted with ixekizumab (12-week interval analyses up to 108 weeks and times to occurrence of infection events). 4] [5] 11, 12  An increased risk of developing active tuberculosis (TB) has been observed with some tumour necrosis factor (TNF)-a blockers.
13 Opportunistic fungal infections (e. g. ] [16] [17]  More recently, interleukin (IL)-17A antagonists have demonstrated substantial clinical effect in patients with psoriasis. 11, 12, 18 1] [22] [23] [24]  Individuals with deficiencies in T helper 17 cells (hyper-IgE syndrome or Job syndrome), IL-17RA or IL-17F exhibit increased susceptibility to mucocutaneous candidiasis and staphylococcal infections. 22, 23 Here we report infections from an integrated database of seven psoriasis clinical trials comprising 4209 patients with 6480 patient-years (PYs) of total ixekizumab exposure. 25.
Study design Data from seven ixekizumab clinical trials are presented in this report (Table  1 , Figs S1, S2; see Supporting Information). 25 ain data sources were UNCOVER-1, UNCOVER-2 and UNCOVER-3, which are randomized, double-blind, placebocontrolled phase III psoriasis trials with a 12-week placebocontrolled induction dosing period. 11, 18, 25 UNCOVER-2 and UNCOVER-3 had an active comparator (etanercept, 50 mg twice weekly) group during the induction period. 11, 25 NCOVER-1 and UNCOVER-2 had a placebo-controlled 48week maintenance dosing period (weeks 12-60). 18, 25  These UNCOVER trials have a long-term extension period to week 264. Trials were registered on clinicaltrials. gov [NCT01474512 (UNCOVER-1); NCT01597245 (UNCOVER-2); NCT01646177 (UNCOVER-3); NCT01777191 (UNCOVER-A); NCT01624233 (UNCOVER-J); NCT01107457 (I1F-MC-RHAJ)].
Safety evaluations There were four integrated analysis sets (Table  1 ). The induction period (weeks 0-12) is represented by the primary placebo-controlled (comparisons with placebo; UNCOVER-1, UNCOVER-2 and UNCOVER-3) and placebo-and active-controlled (comparisons with etanercept; UNCOVER-2 and UNCOVER-3) analysis sets. The maintenance period (weeks 12-60) is represented by the psoriasis maintenance analysis set (this set comprises indution period ixekizumab responders who were rerandomized to ixekizumab or placebo in the maintenance period; UNCOVER-1 and UNCOVER-2). The allixekizumab-psoriasis (AP) analysis set comprises data from all patients treated with ixekizumab from seven clinical trials. The safety population comprised all patients who received at least one dose of the study treatment.
Over 80% of patients with Candida-related events had resolved or resolving infection(s) by the data cut-off per investigator judgement. 25 No reported Candida infections led to treatment discontinuation. Eight patients across all seven trials (IR 0Á1) were reported to have oesophageal candidiasis while receiving ixekizumab or (in one patient) shortly thereafter following rerandomization to placebo during the maintenance period (Table  6 ). 25 Five patients had potential risk factors (≥ 65 years of age, obesity and type 2 diabetes mellitus) for the event reported at baseline. Four patients had oesophageal candidiasis confirmed by oesophagogastroduodenoscopy (EGD). Two reported oesophageal candidiasis events were considered serious from two patients in the ixekizumab Q4W group during long-term extension treatment.
Herpes zoster There were no reports of herpes zoster infections in patients treated with ixekizumab during the induction period (Tables  4 5 ), while two patients treated with ixekizumab were reported to have herpes zoster infections during the Serious infections. Exposure-adjusted incidence rates per 100 PY. The symbol represents the exposure-adjusted incidence rate and the bars signify the 95% confidence intervals (CIs). During the placebo-controlled period the incidence rates for placebo (PBO), ixekizumab (IXE) every 4 weeks (Q4W) and IXE every 2 weeks (Q2W) are from the primary placebo-controlled (PPC) analysis set and the incidence rate for etanercept (ETN) is taken from the placebo-and active-controlled (PAC) analysis set. 25  The 12-60 week maintenance data and all IXE data have been previously presented.
25 9] [30]  Although this range provides context for the prevalence reported here, investigations in large cohorts of immunocompetent white patients and in patients with psoriasis are lacking. Furthermore, no invasive candidiasis or other opportunistic fungal infections were reported for patients treated with ixekizumab, which is relevant given During the placebo-controlled period the incidence rates for placebo (PBO), ixekizumab (IXE) every 4 weeks (Q4W) and IXE every 2 weeks (Q2W) are from the primary placebo-controlled (PPC) analysis set and the incidence rate for etanercept (ETN) is taken from the placebo-and active-controlled (PAC) analysis set. 25  The 12-60 week maintenance data and all IXE data have been previously presented. 25 Ps, psoriasis; DB, double-blind; Q12W, every 12 weeks; LTE, long-term extension; n, number of unique patients with a specific event; RCT, randomized controlled trial; WD, withdrawal.
These results, along with recently published data on the clinical efficacy and overall safety profile of ixekizumab,  11, 18, 25  support a positive benefit-risk profile for ixekizumab, although the analyses used have important limitations. Longterm comparisons of treated and untreated patients were limited as few patients initially randomized to placebo remained on placebo for > 12 weeks. Comparison with etanercept was limited to 12 weeks. Longer-term serious infection rates were consistent with the rates observed in large epidemiological databases,  35, 36  but it remains possible that clinical trial populations do not fully represent the general population with psoriasis. Whereas a significantly greater percentage of patients had infections overall, there were no significant differences by indirect comparison (i.
Whereas the Asian tiger mosquito (Aedes albopictus) has low active dispersal capabilities, its worldwide colonization has been rapid. Indirect evidence and informal reports have long implicated passive transportation in cars, but this has not previously been studied systematically given the difficulties of real-time roadside surveys. Here we report the first sampling study confirming that adult tiger mosquitoes travel with humans in cars and enabling us to estimate the frequency of these events. We combine the results with citizen science data to model the car-facilitated dispersal of Aedes albopictus at a nationwide level. During the summer of 2015, we sampled 770 cars in north-eastern Spain, discovering 4 adult female tiger mosquitoes that had entered cars prior to sampling. Our Bayesian model suggests that of the 6.
05, as can be seen in Supplementary Table  5 ). Evidence from Citizen Science. Our results are corroborated by data gathered by citizen scientists and validated by entomologists during 2014-2016 using Mosquito Alert, a mobile phone application and web platform that helps the general public report tiger mosquito encounters  12, 38. We asked Mosquito Alert participants reporting adult tiger mosquitoes to indicate when their mosquito observations were inside vehicles. During 2014-16 we received a total of 98 reports in which the participant included a note suggesting that the reported mosquito had been discovered in a car or truck. Reports that included photographs were reviewed by a team of entomologists, which concluded that 11 possibly showed tiger mosquitoes, and 16 definitely showed tiger mosquitoes (examples are shown in Fig.
3 ). These 27 possible or definite tiger mosquito vehicle reports account for 1. 3% of the total possible or definite tiger mosquito reports received during the 2014-16 period (2002 reports). We also administered a single-question survey to Mosquito Alert participants, asking them whether they had seen a tiger mosquito in their car during their last car trip. Of the 1673 people who responded, 386 (23%) answered "yes", 1220 (73%) answered "no", and 67 (4%) submitted a blank answer. We do not take this Mosquito Alert data as a reliable indicator of the proportion of cars carrying mosquitoes. As described in the Methods section, we use the validated photographs as the basis for an informative prior in one version of the car transport model, but this is for purposes of robustness checking, and the results are identical to those without the citizen science information.
We do, however, take these citizen science results as evidence, corroborating our car sampling results, that tiger mosquitoes are being transported in cars and that the numbers involved are not trivial. In addition, we use Mosquito Alert data on tiger mosquito prevalence in order to estimate inter-province mosquito transfers, as discussed below. Potential Inter-Province Mosquito Transfers. We take the car stop results as the best available estimate of the probability of a given car transporting a tiger mosquito, and we combine this with data on commuting patterns from Spain's Economically Active Population Survey (APS) and data on tiger mosquito prevalence from Mosquito Alert to estimate potential inter-province flows of tiger mosquitoes in Spain. We find some evidence that car transport probability is positively associated with contemporaneous tiger mosquito prevalence in the municipality in which the car was parked overnight (see Fig.
ITV sampling carried out in 29 sessions from 14 September through 23 October 2015 resulted in an additional 412 cars vacuumed. In total, 770 cars were examined during 106 hours of work (waiting times included). ITV sampling was performed in the line where cars were waiting for the technical checking. The general protocol was identical, except that at the time of vacuuming the driver had already opened the car door once to file paperwork as part of the inspection. The waiting time to enter the test booth was sometimes too short for complete processing, in which case the car had to be discarded from the sample. In both the roadside and ITV sampling protocols, drivers were asked to volunteer to participate anonymously in the study. Refusals were recorded as such, with no other data collected.
We implemented by the Bayesian approach with Stan 52,53 using the rstanarm package for R  54, 55  with weakly informative Cauchy prior distributions with location 0 and scaling factor 2. 5 (equivalent to a student-t distribution with 1 degree of freedom, mean of 0, and standard deviation of 2. 5), as recommended by Gelman et al. 56. We implemented the maximum likelihood estimates using the glm function in R  55. Recapture success was regressed on a constant with no covariates, against the three treatment conditions, and against time and air-conditioning separately and jointly (Supplementary Tables  4 5 ). Citizen Science Data. The citizen science data discussed here comes from Mosquito Alert (previously called Tigatrapp), a scalable system that allows citizen scientists to report tiger mosquito encounters and provide other information through a mobile phone application, collecting data on a server where it is validated by experts and disseminated to public health agencies, mosquito control services, and the public  40.
To keep the flux results conservative, we set the tiger mosquito alert probabilities to zero for all municipalities in which tiger mosquitoes have not yet been officially confirmed. We fit the models using HMC sampling implemented by Stan 52,53 using the rstanarm package for R  54, 55. For all estimated parameters we used weakly informative Cauchy prior distributions with location 0 and scaling factor 2. 5 (equivalent to a student-t distribution with 1 degree of freedom, mean of 0, and standard deviation of 2. 5), as recommended by Gelman et al. 56. We also tried both models using informative priors, as recommended by Rainey  57  as a way of improving and checking the robustness of the logistic regression estimates given the small number of positive observations: For the null model we gave the Cauchy distribution for the intercept a location of 0.
Acknowledgements We are indebted to the  Catalan Police Department  for their contribution under the leadership of  Mr. Albert Batlle. The daily support of all road policemen of the  Àrea Metropolitana Sud  under the direction of  Marc Patxot  and  Josep Sánchez  was essential. Technical stations under the management of ApPlus + collaborated to the study, for which we are grateful to their local managers and to  Victor Salvachúa. Our  gratitude also goes to all drivers who agreed to collaborate with this study by allowing us to sample their cars, and to the entire  Mosquito Alert community. We are grateful to  Moisès Canals  for sampling so many cars, and to  Josefa Doblado  for her trust in lending us her vehicle for the preliminary test. This study has been supported by grant  CGL-2013-34139-R (MINECO ,  Ministerio de Economía y Competitividad , Plan Estatal I + D + i, 2013).
The research associated to Mosquito Alert is supported by the  "la Caixa" Banking Foundation. Mosquito Alert has previously received funding from the  Fundación Española de Ciencia y Tecnología-Ministerio de Economía y Competitividad , the program RecerCaixa-2013, and the company Lokimica S. A. J. P. is funded by the  European Union 's  Horizon 2020 research and innovation programme  under  Marie Skłodowska-Curie  grant agreement No. 657956.
Data and Code Availability. The data and code used in this analysis have been deposited with Zenodo and may be accessed at http://doi. org/10. 5281/zenodo. 838803 (data)  61  and http://doi. org/10. 5281/zenodo. 838797 (code)  62. In addition, the Mosquito Alert data and code, on which the car transport probability model draws, are available at https://doi. org/10. 5281/zenodo. 646531 (data)  63  and https://doi. org/10. 5281/zenodo. 646576 (code)  64. Daily snapshots of the Mosquito Alert data are available at http://doi. org/10. 5281/zenodo. 597466, and all of the code used for the Mosquito Alert mobile phone applications and server is available at https://github. com/ MoveLab.
Estimates of cancer cell fraction based on observed allele frequencies for each driver gene are shown in Supplementary Figure  S2a. STAT3, PIK3CD, and SETD2 show the highest proportion of clonal events among the driver genes. We compared cancer cell fractions (allele frequency adjusted for tumor purity) for pairs of mutations occurring in the same sample (Supplementary Figure  S2b ), and found considerable heterogeneity in the genes that arose as predominant drivers in different cases. In addition, we examined mutation data for the presence of well-characterized driver mutations, even in the absence of a clear somatic event in the discovery set. We identified rare mutations in a number of known driver genes including KRAS (N=3) and CREBBP (N=2) that have been described in other cancers. Additional somatic mutations found and putative driver mutations are shown in Supplementary Table  S3.
Exome sequencing and derivation of genomic data Briefly, genomic DNA was sheared to 250 bp and size/concentration were verified using Bioanalyzer (Agilent Technologies). Sheared DNA was end-repaired, A-tailed, and ligated to Illumina paired-end adapters. The resulting libraries were amplified using Illumina PE specific primers. Samples were column purified and the size and quantity of the final libraries was determined using Bioanalyzer (Agilent Technologies). The resulting libraries were then hybridized for 24 hours to DNA baits provided in the SureSelect Human All Exon 50MB kit (Agilent Technologies). The captured libraries were amplified and sequenced using the Illumina platform. FASTQs were aligned to the hg19 reference genome using BWA-MEM. Indel realignment and base quality recalibration are done with GATK tools.
Here, we report a randomized multicenter phase III trial assessing the lot-to-lot consistency of the 2014-2015 Northern Hemisphere quadrivalent split-virion inactivated influenza vaccine (IIV4; Sanofi Pasteur) and comparing its immunogenicity and safety with that of trivalent inactivated influenza vaccine (IIV3) in younger and older adults (EudraCT no. 2014-000785-21). Younger (18-60 y, n D 1114) and older (>60 y, n D 1111) adults were randomized 2:2:2:1:1 to receive a single dose of one of three lots of IIV4, the licensed IIV3 containing the B Yamagata lineage strain, or an investigational IIV3 containing the B Victoria lineage strain. Post-vaccination (day 21) hemagglutination inhibition antibody titers were equivalent for the three IIV4 lots. For the pooled IIV4s vs. IIV3, hemagglutination inhibition antibody titers were also non-inferior for the A strains, non-inferior for the B strain when present in the comparator IIV3, and superior for the B strain lineage when absent from the comparator IIV3.
Study design This was a phase III randomized clinical trial carried out at three centers in Belgium, three in France, four in Germany, and five in Poland between September 2014 and October 2015 (EudraCT no. 2014-000785-21). Primary objectives were (1) to demonstrate equivalence of the post-vaccination (day 21) HAI antibody response induced by the three different lots of IIV4 for each vaccine strain; and (2) to demonstrate non-inferiority of the post-vaccination (day 21) HAI antibody response induced by the pooled IIV4 lots compared with the IIV3 containing the Victoria lineage strain (IIV3-1) and the IIV3 containing the Yamagata lineage strain (IIV3-2). Secondary objectives were to confirm superiority of the HAI antibody response to the B Victoria lineage strain in the IIV4 group compared to the response to the B Victoria lineage strain in the IIV3-2 group, 21 days after vaccination in younger and older adult age groups; confirm superiority of the response to the B Yamagata lineage in the IIV4 group compared to the response to the B Yamagata lineage strain in the IIV3-1 group; and to describe the safety profile, including solicited reactions during the 7 days following vaccination, AEs during the 21 days following vaccination, and SAEs and AESIs during the 6 months after vaccination.
Safety and reactogenicity Unsolicited AEs and SAEs were collected according to International Conference on Harmonization E2A Guideline for Clinical Safety Data Management: Definitions and Standards for Expedited Reporting. Safety endpoints included immediate unsolicited AEs (within 30 min after vaccination); solicited injection-site reactions (pain, erythema, swelling, induration, ecchymosis) and systemic reactions (fever, headache, malaise, myalgia, shivering) within 7 days, recorded by patients on diary cards; unsolicited AEs within 21 days; and SAEs and AESIs up to 6 months. Erythema, swelling, induration, and ecchymosis were considered grade 1 for 25 to 50 mm, grade 2 for 51 to 100 mm, and grade 3 for >100 mm. Fever was considered grade 1 for 38. 0 C to 38. 4 C, grade 2 for 38. 5 C to 38.
Statistical analysis Statistical analysis was performed using SAS Ò version 9. 2 or later (SAS Institute, Cary, NC, USA). Missing or incomplete data were not replaced, with the exception that all HAI titers under the lower limit of quantitation (10) were assigned a value of 5 and all HAI titers above the upper limit of quantitation (10,240) were assigned a value of 10,240. To calculate GMTs, the means and 95% confidence intervals (CIs) were determined from log 10 -transformed data using Student's t-distribution with n¡1 degrees of freedom, after which antilog transformations were applied to the results of calculations. Lot-to-lot consistency and non-inferiority of IIV4 vs. IIV3 were assessed in all participants who completed the study according to protocol. Superiority of IIV4 vs. IIV3 was assessed primarily in all vaccinated participants.
Inhibitory checkpoints expressed by human T lymphocytes and ILCs. This fi gure was generated based on literature for receptors whose expression has been demonstrated by surface staining (T cells, NK cells, and ILC-2s) and on microarray data available in public databases for relative quantifi cation of transcripts (italics) when no information of surface expression has been reported (ILC-1 and ILC-3). This listing does not preclude the expression of other inhibitory receptors, for instance under various stimulation conditions. Receptors are in bold, whereas their cognate ligands are in normal characters. similarly as cancer cells do in their microenvironment. In vitro culture with IL-33 up-regulated PD-L1 expression on ILC-2s, suggesting that ILC-2s could inhibit each other. These fi ndings need to be demonstrated in vivo to show whether epithelial cells activated during helminth infection can indeed inhibit ILC-2 responses by releasing IL-33.
Tissue Preparation for histology and immunohistochemistry Lungs and livers from M. tuberculosis-infected mice collected on days 25-28 and 56 were fixed in 4% buffered formalin and paraffin-embedded, and 4 µm sections were stained with hematoxylin and eosin (H&E) or underwent the Ziehl-Neelsen coloration. Sections were observed by light microscopy at 400× magnification with a Zeiss Observer D1 microscope equipped with a motorized stage connected to Histolab and Archimed software (Microvision, Les Ulis, France). The number and size of granulomas were quantified by using Archimed. For immunohistochemistry, lung and liver sections were fixed in acetone-ethanol (5 min), and endogenous peroxidase activity was blocked with PBS and 3% H2O2. Endogenous biotin in the liver was blocked by using an avidin-biotin kit (Vector Laboratories, SP-2001).