dataesr/scientific-paragraphs-categorization huggingface dataset:
In contrast, the database and patient-reported exacerbation measures had equivalent 12-month assessment periods and so were more comparable. Patient reports are subjective measures and potentially open to both over-and underreporting. Apparent overreporting may have occurred in patients who received treatment for more than one exacerbation from a single oral steroid prescription, while underreporting may have occurred as a result of poor patient recall, especially when asked to report events over a 12-month period. Equally, under-or over-recording may occur within database measures as a result of (among other issues) incomplete data. The OPCRD, for example, is known to underreport severe exacerbations because of the lack of automatic entry within primary care records of secondary care events -only those that are manually entered by the primary care clinician are captured.
This is most likely a systematic underreporting and, as such, should not affect comparative analyses between consecutive time periods (baseline/outcome years), but will diminish study power. Overreporting of oral steroid prescriptions may be present in the database if one or more courses are prescribed for ad hoc requirements in association with an action plan and not actually needed by the patient. For all the above reasons, strong agreement was not expected between the database outcomes and PROs, although both offer differing insights and perspectives: of health care resource utilization and the patient experience, respectively. Limitations of each data measure must be acknowledged in the literature and, where possible, addressed through data linkage and triangulation of results.
Utility of database outcomes RDac The definition of RDAC examined in these analyses is essentially equivalent to an absence of exacerbations in the patient's recent history and, in this analysis, was assessed over the 12-month period before and after ICS initiation or step-up. It was found to be responsive to ICS use, as the proportion of patients with uncontrolled asthma by RDAC decreased following treatment initiation and step-up. Baseline RDAC, as well as several of its components, was found to be associated with future exacerbations in our univariable analyses. Exacerbations included in RDAC were accident and emergency attendance, acute courses of OCSs, and respiratory-related prescription of antibiotics. These findings are consistent with other asthma risk prediction studies, which particularly noted the importance of previous ED attendance.
29 For these reasons, the use of an outcome that includes SABA prescribing may be misleading if used in database studies that aim to evaluate the effectiveness of therapy. SABA prescribing may still be valuable, however, when investigating the risk of future asthma outcomes, as dispensing of three or more SABA inhalers in a year is associated with a greater risk of exacerbations,  30  and dispensing of ≥12 SABA inhalers in a year is associated with a greater risk of asthma-related deaths. 31 In the univariable models, OAC and its disaggregated SABA component were both predictive of future exacerbations. exacerbations Database-defined exacerbations were found to be a responsive measure: the mean number of exacerbations per year decreased from 0. 09 to 0. 08 following the initiation of ICS and decreased from 0.
strengths and limitations This study used data from a large, well-validated database and is representative of patients with asthma in a real-life primary care setting. 7] [18]  We investigated definitions of asthma control that represented the two domains of asthma control recommended by the ATS/ERS Task Force,  14  namely current clinical control (now often called symptom control), assessed over the previous 1-4 weeks, and future risk (ie, individual risk factors for adverse outcomes such as exacerbations). Database severe exacerbations were defined in line with a definition previously proposed by expert working groups. 14, 32 However, prescribing of antibiotics with evidence of respiratory review may not be optimal for identifying exacerbations, as there are strong recommendations against treatment of asthma exacerbations with antibiotics, and changes over time may reflect interventions to reduce use of antibiotics rather than changes in asthma control.
The limitations of this study include the inconsistency in age ranges across cohorts (perhaps representing the different periods of data collection and/or better adherence with questionnaire return by older patients), and the time frame of the study, as data were extracted over a 25-year period over which management approaches have evolved. Lung function assessment was not included in the present assessment of asthma control. In the past, lung function was combined with symptoms and reliever use in the assessment of asthma control, but since the 2014 GINA revision, lung function has instead formed part of initial and ongoing risk assessment. 33 he rationale for this change was the known discordance between symptom measures and lung function measures, and the strong association between low lung function and increased risk of exacerbation.
33 e based one of the study cohorts on a step-up of ICS to medium dose; however, this does not align with current UK guidelines, in which the primary recommendation is step-up to low-dose ICS/LABA. As above, the database measure of SABA dispensing over a year proved not to be a satisfactory proxy for recent asthma symptom control. Given the present findings, further analyses would be of interest, including the responsiveness of PROs and the investigation of additional independent risk factors for exacerbations such as current smoking that may be included in EMRs. 9 urthermore, examination of a control group would be helpful when investigating responsiveness, to identify changes in the proportion of patients with "controlled" asthma or mean number of exacerbations in the same time period in a cohort in which there were no changes to therapy.
Finally, results may not be applicable to other countries in which EMR data may differ from those in the UK. 34 plications for database studies The findings from this study support the use of databasederived RDAC and exacerbations to evaluate real-life effectiveness of asthma therapies and should increase the confidence in observational research that utilizes these outcomes. Apart from allowing the analysis of large sample sizes, database measures have the benefit of being objective and routinely recorded and therefore can be evaluated in unselected real-world patient groups. Bias may arise, however, when relying on the events and prescriptions that are identifiable through an electronic database, as aspects of actual patient experience may be masked. For example, the real-life outcomes in this study may have failed to identify multiple exacerbations if the number of OCS tablets dispensed from one prescription was sufficient to treat more than one exacerbation, and the number of SABA prescriptions over a year performed poorly as a measure of asthma control.
The validation of database outcomes is important, as the administrative datasets from which they are derived are not typically maintained for research purposes. Furthermore, there is the possibility of data entry errors or incomplete data entry, either at random or systematically. 35, 36 Issues arising from database studies should always be transparently reported. Database outcomes could be most useful in future risk studies and to differentiate between risk profiles of different asthma phenotypes. The identification of at-risk phenotypes requires large studies including heterogeneous patient populations, which can be infeasible within prospective studies and, although lacking RCTs' traditional requirement for strong internal validity, may have high external validity in their generalizability to real-world populations.
Conclusion Database and patient-reported asthma outcomes offer different, potentially complementary, insights into the "reality" of asthma, but they must be thoughtfully selected, clearly described and appropriately interpreted when designing, conducting and reporting observational research. Database asthma measures of RDAC and severe exacerbations are responsive descriptions of asthma health status that may be useful in the evaluation of real-life asthma treatment effectiveness and future exacerbation risk.
Data sharing statement The dataset supporting the conclusion of this article was derived from the Optimum Patient Care Research Database (www. opcrd. co. uk). The authors do not have permission to give public access to the study dataset; researchers may request access to OPCRD data for their own purposes. Access to OCPRD can be made via the OCPRD website (https://opcrd. co. uk/our-database/data-requests/) or via the enquiries email info@opcrd. co. uk. The study was designed, implemented, and registered in accordance with the criteria of the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP; registration number: EUPAS13194).
Study population and study design We conducted a retrospective cohort study approved by the local Ethics committee of Angers University Hospital (agreement 2014-84, approved on october, 2014). Given the retrospective nature of the research, patients did not provide written consent, although verbal consent was required by the Ethic Committee for kidney transplant patients with IgA nephropathy. Verbal consent was obtained from patients during their standard medical follow-up in the department. All consecutive patients who underwent kidney transplantation in Angers University Hospital between January 2003 and December 2013 (n = 471) were considered for inclusion in the study. Patients were followed until graft loss or death. Patients with missing data at the time of transplantation were excluded.
Data allowing the characterization of the study population were retrieved from the department's database and the French Transplantation database (Cristal, Agence de la Biomedicine). None of the transplant donors were from a vulnerable population and all donors or next of kin provided written informed consent that was freely given. We collected the following clinical parameters: gender, age, weight, body mass index (BMI), treatments including immunosuppressive regimens and antihypertensive medications. Hypertension was defined as systolic blood pressure (SBP) >140 mmHg and/or diastolic blood pressure (DBP) >90 mmHg or treatment with antihypertensive drugs. We recorded the following biological parameters: 24 h urinary protein excretion, serum albumin (sAlb), serum creatinine (Scr), hemoglobin (Hb) and levels of serum Ig (IgA, IgG, IgM).
Statistical analysis Continuous variables were expressed as a mean ± SD and categorical variables as absolute number and percentage. Categorical and continuous data were analyzed with χ 2 or Fischer's exact test and Mann-Whitney U tests, respectively. The predictive values of sIgA, serum creatinine and proteinuria at month 6 and month 12 post-transplant for IgAN recurrence were analyzed using receiver operating characteristics (ROC) curves. Subsequently, a cut-off value of sIgA was determined based on the Youden index from the ROC curve at month 6 post-transplant. Univariate and multivariate logistic regression were used to analyze the risk factors associated with the presence of post-transplant IgAN recurrence. Associations are given as odds ratios (ORs) with 95% confidence intervals. Kaplan-Meyer method was used to analyze free survival of IgAN recurrence.
We finally analyzed survival free of IgAN recurrence according to the presence or not of sIgA level above to 222. 5 mg/dL as determined by ROC analysis. By using this cut-off, survival free of IgAN recurrence was significantly higher in patients who had serum IgA level below 222. 5 mg/dL, as compared to patients who had sIgA above 222. 5 mg/dL. These results are in part consistent with data from literature. Indeed, in a previous work, Zhang et al identified sIgA/C3 ratio as an independent risk factor for progression of IgAN in non-transplant patients  [18]. In multivariate analysis, progression of IgAN was significantly predicted by serum IgA/C3 ratio  [18]. Recently, Berthelot et al showed that pre-transplant serum levels of galactose-deficient IgA1 (Gd-IgA1) and IgA-IgG complexes were significantly higher in patients with IgAN recurrence compared to patients without or healthy subjects.
50 -1. 5 g/l that is to say (0. 70 -1. 70 mmol/l). Total Cholesterolemia: normal if comprises between 1. 5 -2. 20 g/l that is to say (3. 88 -5. 68 mmol/l). HbA1c: inferior or equal to 7%. Data Analysis: The processing and analysis of the data were done through the softwares SPSS version 10. 0 and Microsoft Word Office 2007. We have retained p < 0. 05 as the point of signification for statistical tests.
Background: An impairment of the peripheral nervous system has been suggested in fibromyalgia (FM). Noninvasive distal electrochemical skin conductance (ESC) has been studied little so far when combined with quantitative sensory testing (QST) in patients with FM. Methods: This study (clinicaltrials. gov NCT03347669) included 50 female patients with FM and 50 matched healthy volunteers (HVs). ESC (measured in microsiemens [µS] with Sudoscan), as well as psychological, quality of life, sleep, and social characteristics, were assessed in both groups. In a subgroup of 24 patients with FM and 24 HVs, QST of cold and warm detection and pain thresholds and diffuse noxious inhibitory controls (DNICs) were explored. Statistical analysis was performed for a 2-sided type I error at 5%. Results: Between patients with FM and HVs, ESC values differed (71.
Statistical Methods Considering the number of subjects, it is estimated that 30% to 50% of patients with FM may have an SFN. 14, 37 hus, a sample of 50 patients should provide a margin of error of 5% to 6% of the 95% confidence interval (CI) for the prevalence of SFN. This number would make it possible to demonstrate a difference in terms of SFN between 50 patients with FM and 50 HVs on the order of 30% (1% vs. 30%) for a risk of error of first bilateral species of 5% and a power of >90%. Statistical analysis was performed using STATA software (version 13; StataCorp, College Station, TX, U. S. A. ) for a 2-sided type I error at 5%. Continuous data were described as mean AE standard deviation or median [interquartile range] according to the statistical distribution. The assumption of normality was assessed using the Shapiro-Wilk test.
CONCLUSION Collective data obtained in this study show that the sudomotor function measured by ESC in patients with FM is significantly diminished on the dominant hand. This impairment parallels the changes of thermal detection and pain thresholds in the context of absent spinal pain modulation by DNICs. It appears then as a local peripheral phenomenon with a lateralization on the dominant side of the body and/or a central modulation of the autonomic system at hemispheric or insula levels bypassing the DNICs. ESC values combined with QST values are relevant in the context of patients with FM and need to be explored further in this complex nociception-autonomic system intertwining.
female patients with FM and 50 HVs. It was carried out in the Clinical Pharmacology Centre/ CIC Inserm-1405, University Hospital, Clermont-Ferrand, France, according to good clinical practice. The French Research Ethics Committee gave its approval on October 5, 2017 (ethics committee number IORG_404310/reference 2017-47-2); this trial is regis- tered in ClinicalTrials. gov (trial number NCT03347669). The study took place from November 2017 to September 2018.
Participants Seventy-four German native speakers all living in the Potsdam area (Brandenburg) were invited to take part in the study. We ensured none of the participants showed any regional influence on their speech. They were divided into four children age groups: nineteen 3-year-old children (10 girls, age range: 3;05-3;09 [years;months], M = 3;06), fourteen 4-year-old children (seven girls, age range: 4;04-4;08, M = 4;05), fourteen 5-year-old children (seven girls, age range: 5;04-5;07, M = 5;06), and fifteen 7-year-old children at the end of the first or beginning of the second grade in primary school (10 girls, age range: 7;00-7;06, M = 7;02). All children cohorts were selected from the large database of the Baby Lab at Potsdam University. They were enrolled in kindergarten and primary schools in Potsdam.
Experimental Procedure The study took place at the Laboratory for Oral Language Acquisition at the University of Potsdam (Germany). Participants were recorded within the SOLLAR platform (Sonographic and Optical Linguo-Labial Articulation Recording system; Noiray, Ries, & Tiede, 2015). SOLLAR is a child-friendly custom-made platform for the recording and analysis of data from multiple sources (e. g. , the tongue using ultrasound imaging with fps: 48 Hz, the lips using video camera with fps: 50 Hz, the audio speech signal via microphone with fps: 48 KHz). It has been designed as a space rocket to be used with young children. To stimulate children's interest and motivation to complete the study, the production task was embedded in an interstellar journey. The ultrasound probe used for imaging the tongue is fixed in a custom-made probe holder that is integrated in the space rocket.
Data Processing The acoustic signal was recorded together with the video from the ultrasound device and the video camera, enabling the generation of a common time code for subsequent data synchronization (via a cross-correlation function within MATLAB; cf. Noiray et al. , 2013 Noiray et al. , , 2015)). First, the acoustic data were phonetically labeled using Praat  (Boersma & Weenink, 1996). For adults, target words and segments were segmented semiautomatically using WebMAUSBasic  (Kisler, Schiel, & Sloetjes, 2012)  and manually corrected when necessary. For all children, native speakers of German manually labeled all target words and segments, using as vocalic reference stable periodic cycles in the oscillogram and stable formant pattern, especially a clearly detectable second formant. In addition, the first ascending zero-crossing in the oscillogram at the beginning of the periodicity was used as schwa and vowel onset; the first ascending zerocrossing after the end of periodicity and disappearance of F2 was used as the beginning of the medial consonant.
g. , /aɪnə ba:tə/ was kept for model /aɪnə ba:də/). Ultrasound video frames corresponding to the five target time points (i. e. , the midpoint and offset of the schwa, the midpoint and offset of the consonant, and the midpoint of the target vowel) were extracted automatically using the SOLLAR platform  (Noiray et al. , 2015). For each ultrasound frame, tongue contours were semiautomatically detected with scripts custom-made for MATLAB as part of the SOLLAR platform. For each ultrasound frame, a 100-point spline was automatically fit to the midsagittal tongue surface contour. x and y Coordinates for each of the 100 points of these splines were then automatically extracted. In this study, we used values for the highest point of the tongue dorsum surface contour in the x-coordinate reflecting the anterior-posterior position of the tongue dorsum.
Preliminary Considerations Before running statistical analyses, data were made comparable across participants. We set the most anterior position of the tongue dorsum position during all of the vowel pronunciations (at the midpoint of the vowel: V50) to 0 and the most posterior V50 position to 1. For all other relevant time points, tongue dorsum positions in the anteriorposterior dimension were scaled in this range (i. e. , negative values or values greater than 1 are possible if there are more extreme positions or posterior positions of the tongue dorsum during the pronunciation of the consonant [or the schwa]). To assess potential nonlinear patterns over time, we used GAM. While this approach has been used to model the tongue's trajectories measured by electromagnetic articulography  (Wieling, 2018; Winter & Wieling, 2016) , to our knowledge, this is the first time GAM has been applied to ultrasound tongue imaging data in the developmental field (but see  Strycharczuk & Scobbie, 2017, in adults).
| Confocal microscopy The images were acquired using a Nikon Ti inverted microscope in combination with an A1 spectral confocal scanning head. For all GFP fusion proteins, excitation/emission wavelengths used were 488 nm/505-555 nm. For mVenus, excitation/emission wavelengths were 514 nm/525-555 nm. For mCherry and RFP, excitation/emission wavelengths were 561 nm/570-620 nm. The analysis of the images was performed using Fiji (http://fiji. sc) software. Using a confocal microscope with a 60× objective did not yield a resolution high enough to distinguish between the apical membrane of one cell and the basal membrane of the neighbouring cell. For AUX1-mVenus, we measured both and added them up to create the apical/basal component. All images were corrected for background signal. Membrane intensity quantification was done using ImageJ, for all cells the average pixel intensity for the apical side (or apical/basal in the case of AUX1 and Plasma Membrane Proton ATPase 2 [PMA2]), and both lateral sides of the PM and the intracellular signal were measured by drawing a region of interest by hand.
| Main modelling assumptions To apply the experimentally obtained data to our (halo)tropism model, we needed to make two key assumptions. First, salt-induced effects on intracellular and membrane protein patterns were measured under experimental conditions in which salt was uniformly applied to the plant roots. To extrapolate these findings to halotropism where salt stress occurs (predominantly) at a single side of the root, we assumed that the experimentally observed changes in PIN2 and AUX1 occur in a similar manner but only at the salt-exposed side of the root. Second, in contrast to our earlier work, microscopic images were obtained using a longitudinal epidermal top view rather than a longitudinal cross section of the root. As a consequence, in addition to apical and basal membranes, radial rather than transversal lateral membrane faces were imaged.
ACKNOWLEDGEMENTS We thank  Remko Offringa  ( PIN2-GFP ),  Malcolm Bennet  ( AUX1-mVenus ),  Niko Geldner  (wavelines  W2R ,  W22R , and  W34R ;Geldner et al. , 2009),  Karin Schumacher  ( VHA1-RFP  and  PMA2-GFP ), and  Eva Benkova  ( PIN3-GFP ) for kindly sharing published materials. We thank  Michel Haring  and  Teun Munnik  for critical reading. This project was funded by  NWO  ( CW 711. 014. 002  and  Vidi 864. 14. 003 ).
Cytotoxicity and caspase activity assays For cytotoxicity assays, 8 × 10 4 cells or 5 × 10 5 cells (for p493-6 p53shRNA) per well of a 96-well plate were treated in triplicate with DMSO, 3 μM CHIR, or 5 ng/mL tetracycline and indicated concentrations of Dox or TRAIL. After 48-72 hours, cell viability was measured using CellTiter-Glo (Promega, G7570) according to the manufacturer's protocol. Luminescent signal was read using a Synergy 2 plate reader (BioTek Instruments, Winooski, VT, USA). GraphPad Prism software (version 7) was used for log-transformed nonlinear regression curve fitting (4 parameter analysis). For caspase activity assays, cells were treated with DMSO or 3 μM CHIR and indicated concentrations of Dox or vincristine. 5 × 10 4 cells were plated in triplicate in a 96-well plate and caspase activity was measured using Caspase-Glo 3/7 Assay (Promega, G8091).
Once tumors became palpable, mice were treated with CHIR99021 and/or Dox as described above. The model was developed in female NSG mice of 6-8 weeks at engraftment within the project Development of Pediatric PDX Models, approved by the experimental ethic committee 26 (CEEA26-Gustave Roussy) under the number 2015032614359689v7, and in accordance with European legislation, as ancillary study of the clinical MAPPYACTS trial (ClinicalTrials. gov identifier ).