dataesr/scientific-paragraphs-categorization huggingface dataset:
, VanRullen and MacDonald 2012). Observers gave their response by button press after the trial was complete. In experiment 2, the target appeared on only one side (left or right patch) chosen randomly for each appearance. The square followed the same luminance sequence with a certain offset controlling task difficulty. This offset was varied adaptively in a staircase procedure to keep the observer's detection rate fixed at ∼84%. Stimulus presentation in both experiments was controlled by a Linux computer, using MATLAB version 9. 6 (The MathWorks) and the Psychophysics Toolbox  (Brainard 1997).
EEG Recordings EEG data were recorded continuously during stimulation using a 64-channel active Ag/AgCl electrode system (actiCHamp amplifier module, Brain Vision LLC). Electrodes were fixed to the head with a cap and impedances brought to 5 kΩ prior to the start of recording. The signals were digitized at a sampling rate of 1 kHz using the PyCorder software (Brain Vision LLC) and stored for offline analysis. An EyeLink 1000 system (SR Research) was used to aid eye movement and blink artifact detection in experiment 1. In experiment 2, for the same purpose, a vertical EOG was recorded through two additional electrodes positioned above and below the left eye, with a ground electrode fixed to the forehead.
Impulse Response Functions From the continuous EEG recording, epochs were defined based on the onset times of the stimulus patch in each trial. The first and last 500 ms of the presented 6. 25 s sequences were discarded to limit analysis to the steady-state response. The resulting epochs were re-referenced to the linked mastoids, band-pass filtered between 2 Hz and the maximum frequency in the stimulus sequence (experiment 1: 60 Hz; experiment 2: 120 Hz) using a two-pass fourth-order Butterworth IIR filter, and resampled to stimulus frame rate. Trials containing gross eye movements or blinks were discarded, based on eye-tracking data (experiment 1) or EOG recordings (experiment 2). For each trial and electrode, the EEG epochs were z-scored and cross-correlated with the presented stimulus sequence: IRF(x) = t stim(t) • EEG (t + x) where t is the time variable of the trial in samples, and x is the lag between stimulus (stim) and the recorded EEG.
Study design and population This is a cross-sectional study using prospective data from the French National Sleep Apnea Registry (Observatoire Sommeil de la Federation de Pneumologie [OSFP; www. osfp. fr]). The methodology and participants of the registry have been described in detail elsewhere  [9, 24, 25]. In brief, the registry is a web-based report administered by the French Federation of Pulmonology. It contains standardized, anonymized, longitudinal data of patients referred for suspected sleep-disordered breathing, assessed by respiratory physicians working in private practice and general or university hospitals. Among 100,759 patients included in the OSFP database from January 1997 to January 2017, 72,376 patients had completed a sleep study within 6 months of the first medical visit and were flagged for analysis in the present study.
A subgroup of 46,786 patients >18 years old with an apnea-hypopnea index (AHI) �15 and/or oxygen desaturation index (ODI) �15 was then selected to assure a robust diagnosis of sleep apnea. Valid measurement of forced expiratory volume in 1 second (FEV 1 ) over forced vital capacity (FVC) was available for 16,466 patients (Fig  1 ). Demographic data and medical history were collected during the baseline evaluations, including diagnosis of cardiovascular comorbidities made by a physician. Symptoms were evaluated using standardized questionnaires. Ethics committee approval to set up the study database was obtained from the French information technology and personal data protection authorities (C. C. T. I. R. S n˚09. 521). The OSFP Independent Scientific Advisory Committee approved the use of this database for the present study.
05) and included in a multivariable logistic regression model. A stepwise forward selection method was used to define the final multivariable model. Statistical interaction between FEV 1 and AHI on cardiovascular outcomes was non-significant when tested in a logistic model (P values of >0. 15 for all cardiovascular outcomes). Logistic regression models were also used to test the effect of type of sleep study (type III or type I), age, gender, BMI, smoking status, AHI and COPD on cardiovascular outcomes. The collinearity between factors was tested. Log linearity between the variables was tested and the variables were transformed into categorical variables if necessary. Statistical analyses were conducted with SAS v9. 4 (SAS Institute Inc. , Cary, NC). Results were considered significant at P values of 0.
Study population A total of 16,466 patients with available spirometry data were included in the present analysis. The clinical characteristics are presented in Table  1. Among these, 14,368 (87%) had OSA and 2098 (13%) had OVS. Clinical characteristics of 16,466 OSA patients who were offered spirometry compared to 30,320 OSA patients without available spirometry data are available in the online supplementary S1 Table. By definition, OVS patients had a median FEV 1 /FVC ratio of 64% (interquartile range [IQR] 59 to 67) compared to OSA patients who had a FEV 1 /FVC ratio of 82% (IQR 77 to 87. 9) (P <0. 01). Median FEV 1 (% predicted) was 75 (IQR 60. 0 to 88. 1) in OVS patients and 97 (IQR 86. 0 to 107. 7) in OSA patients (P <0. 01). GOLD stages were: 1: 863 (41%); 2: 976 (46. 5%); 3 and 4 combined: 259 (12.
This is of particular importance when considering the cardiovascular risk in OVS patients  [22]. Previous observational studies have suggested a synergistic impact of COPD and OSA on cardiovascular disease  [21, 22, 41, 42, 43]. Although these studies generally reported a higher prevalence of cardiovascular disease in OVS, they were flawed by small sample sizes and poor characterization of the respective contribution of OSA and COPD. A recent review  [44]  stated that "careful consideration of the severity of both OSA and COPD is required when determining the significance of OVS as a clinically relevant entity" associated with hard outcomes. This is the case in our current dataset demonstrating that decreasing lung function, in addition to moderate-to-severe OSA, had different effects on different cardiovascular traits.
However, it is difficult to speculate why an increasing severity of COPD increased the prevalence of coronary heart disease, heart failure and peripheral arteriopathy in a dose-response manner, while prevalent hypertension and stroke seemed not to be affected. Available evidence only suggests that sympathetic activation associated with OSA is more important in systemic hypertension  [45] , whereas systemic inflammation associated with COPD may play a greater role in the pathogenesis of atherosclerosis and coronary heart disease  [46]. Our study has several strengths and limitations. We report here the largest OVS population to date. Both OSA and COPD severity were objectively assessed and allowed subgroup analyses. In such a well-maintained registry, a careful analysis of confounders allowed reporting an association between COPD and cardiovascular health in OSA patients  [47]  but causality remains to be firmly established by incident data and randomized controlled trials as our study design only allows generating hypothesis.
A selection bias is possible since pulmonary function tests were conducted only in a large subset of patients, but not in the whole population referred for a suspicion of OSA  [30]. However, a prevalence of OVS around 13% and an analysis of the clinical characteristics of 16,466 OSA patients with available spirometry data compared to 30,320 OSA patients without spirometry data did not bring to light major differences between populations to support a significant selection bias. Regarding dataset, we Graphic illustration of how OSA and COPD interact to impact on cardiovascular health. The probability of having hypertension was higher in severe OSA (AHI �30) compared to non-severe OSA (AHI <30) and was not impacted by COPD. In moderate-to-severe OSA, COPD was associated with a higher probability of having coronary heart disease, heart failure, particularly peripheral arteriopathy, in a dose-response relationship.
COPD did not increase the prevalence of stroke in OSA, irrespective of its severity. Odd ratios are adjusted on age, gender and smoking status. Numerical data are provided in Table  4. https://doi. org/10. 1371/journal. pone. 0235331. g002 acknowledge two more limitations: (i) the majority of centers were using a 3% desaturation and a micro arousal ending the event for hypopneas scoring during polysomnography and reduced flow associated with a 3% desaturation for hypopnea scoring during type III sleep recording. Owing to the size of the registry it was impossible to use a centralized scoring for all sleep studies but we did not observe major differences in AHI between polysomnography and type III sleep recording (not reported); (ii) no detailed information on the type of stroke was available in this large registry.
This study was funded by an unrestricted grant from " Appel d'offre cohorte-fondation du souffle " ( SRC_2017 ) to JLP and RT. RT and JLP are supported by a research grant from the  French National Research Agency  ( ANR-12-TECS-0010 ) in the framework of the " Investissements d'avenir" programme  ( ANR-15-IDEX-02 ) and the "e-health and integrated care" Chair of excellence of the  University Grenoble Alpes Foundation. DA is supported by research grant  LPS-16/12  from the " Ligue Pulmonaire Suisse " to conduct a programme entitled "integrated care of patients surviving acute hypercapnic respiratory failure in the ICU. ".
Impulsivity is a multidimensional phenomenon that remains hard to define. It compounds the core pathological construct of many neuropsychiatric illnesses, and despite its close relation to suicide risk, it currently has no specific treatment. Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique whose application results in cognitive function improvement, both in healthy and psychiatric populations. Following PRISMA recommendations, a systematic review of the literature concerning tDCS's effects on impulsive behaviour was performed using the PubMed database. The research was based on the combination of the keyword 'tDCS' with 'impulsivity', 'response inhibition', 'risktaking', 'planning', 'delay discounting' or 'craving'. The initial search yielded 309 articles, 92 of which were included.
Search strategy This systematic review was conducted in accordance with PRISMA guidelines recommendations  (36). Two authors (JTM and DB) independently screened the PubMed database until December 2018. The search strategy was based on the combination of the keyword 'tDCS' with each one of the following terms ('tDCS AND'): 'impulsivity', 'response inhibition', 'risk-taking', 'planning', 'delay discounting' or 'craving'. The keywords were chosen in accordance with current perspectives on the multidimensional construct of impulsivity  (1, 2, 4, 5, 7, 8, 37). There was no restriction on the date of publication. Following de-duplication, studies were sorted by title and then abstract, with the full text of potentially relevant articles obtained in order to conduct a quality assessment and make a decision regarding their inclusion in the final sample.
Statistics Data were analyzed using Two-way ANOVA followed by Tukey's or Sidak' multiple comparison tests or Mann Whitney test (for less than 2 groups). Non-normally distributed data were analyzed by the corresponding non-parametric tests. Statistical analysis was carried out using GraphPad Prism 8 software. Data were presented as mean ± standard error of the mean (SEM) for all statistical analysis. A P value of less than 0. 05 was considered significant.
Statistical analyses The majority of data populations illustrated in Figs 1, 3 and 4 showed non-normal distributions (verified using Shapiro-Wilk normality test at 0. 05 significance level). Therefore, a nonparametric test (Wilcoxon-Mann-Whitney rank sum test) was employed for the comparison between different groups of data. The resulting p-values were adjusted with the Bonferroni correction for multiple testing. Note that only p-values < 0. 01 were considered to reduce the chances of false positives (type I errors). The sample size n always refers to the number of biological replicates (independent preparations). The activity of each independent preparation was determined as mean over three technical replicates. The average scatter within technical replicates was 3 times smaller than the scatter across biological replicates for a given treatment.
For dose-response analyses, we used the nls function from the stats package in R (version 3. 5. 1) to model the data points with the Hill-Langmuir equation, y x; ED 50 ; n; y sat ð Þ ¼ y 0 þ y sat x n ED 50 n þ x n ; ð1Þ where y is the Tl + uptake of HEK rnKCC2b cells, y 0 is the Tl + independent-baseline activity (y 0 = 100%), y sat is the maximum activity (equivalent to V max in reaction rate equation) relative to baseline, x is the concentration of the agonist, n is the Hill coefficient, and ED 50 is the agonist concentration that produces 50% of the saturation response. The 95% confidence intervals for the dose response curves were determined with the function NonlinearModelFit ["MeanPre-dictionBands"] in Wolfram Mathematica. For the boxplots, the box extends from the upper (Q1) to the lower (Q3) quartile.
Figures were generated using Photoshop/Illustrator (Adobe). Band densities of bands were measured with ImageJ. Calculation of intensity ratios is based on (phospho-dimeric KCC2 + phospho-monomeric KCC2) / (total dimeric KCC2 + total monomeric KCC2), (total dimeric KCC2 + total monomeric KCC2)/β-actin or tubulin, SPAK pThr 233 /SPAK, SPAK pSer 373 /SPAK, SPAK/β-actin or tubulin, NKCC1 pThr 203,207,212 /NKCC1, NKCC1/β-actin or tubulin, as reported previously  [66]. Mann-Whitney U-test was used for comparison between 2 independent groups and Wilcoxon matched pairs test was employed to compare paired data (GraphPad Prism 7. 0, San Diego, CA, USA). For phospho-antibody immunoprecipitation, KCC isoforms were immunoprecipitated from indicated cell extracts. 2 mg of the indicated clarified cell extract was mixed with 15 μg of the indicated phospho-specific KCC antibody conjugated to 15 μl of protein-G-Sepharose, in the added presence of 20 μg of the dephosphorylated form of the phosphopeptide antigen, and incubated 2 hours at 4 ˚C with gentle shaking.
Upon treatment with staurosporine or NEM, Ser 382 of hsWNK1 and Ser 372/373 of hsSPAK were not detected anymore (Table  4 ). We were not able to detect phosphorylation of Thr 233 that is located in the T-loop kinase domain of hsSPAK. Normally, this site is directly phosphorylated by WNK1 and WNK4 to activate SPAK  [60, 63, 69,  Table  1. Phospho-sites of stably transfected HEK rnKCC2b cells. Stably transfected HEK rnKCC2b were treated with or without 1 mM NEM or 8 μM staurosporine before they were analyzed by mass spectrometry. The protein accession numbers are: hsNKCC1 (P55011), hsKCC1 (Q9UP95), rnKCC2b (Q9H2X9-2), hsKCC4 (Q9Y666).
Whereas NEM resulted in increased KCC2 amount (p = 0. 0026), no obvious change was detected upon staurosporine treatment. NKCC1 and SPAK levels were not changed significantly upon treatment with either agent. To conclude, staurosporine and NEM reduced the phosphorylation status of SPAK (Thr 233 and Ser 373 ). This correlated with the reduction of the phosphorylation of Thr 1007 in rnKCC2b Table  4. Phospho-sites of hsPKC endogenously expressed in stably transfected HEK rnKCC2b cells. Stably transfected HEK rnKCC2b were treated with or without 1 mM NEM or 8 μM staurosporine before they were analyzed by mass spectrometry. The protein accession numbers are: hsPKC Alpha (P17252), hsPKC Beta (P05771-2), hsPKC Delta (Q05655), hsPKC Epsilon (Q02156), hsPKC Theta (Q04759), hsPKC Eta (P24723), and hsPKC Iota (P41743).
This work was supported by the  Deutsche Forschungsgemeinschaft  (grants  NO428/14-1  to H. G. N; and  HA 6338/2-1  to A. -M. H). The work was further funded by  Max-Planck Society for the Advancement of Science  by the  German Research Foundation (DFG/Gottfried Wilhelm Leibniz Prize  to J. R. W. ) and the  National Natural Science Foundation of China  (No. 81970238  to J. Z. ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
84%) in the ophthalmic branch of the TG of DED mice compared to sham animals (sham: 0. 31 ± 0. 03 vs. DED: 1. 10 ± 0. 21, p < 0. 05; Figure  2B ). For statistical analysis, the Kolmogorov-Smirnov test was performed followed by a nonparametric Mann-Whitney using GraphPad Prism version 7. 00 (GraphPad Software, La Jolla, CA, USA).
Instillation of M8-B Reduced Ongoing and Cold-Induced Electrical Activities of Thermoreceptors in ex vivo Eye Preparations from DED Animals Ongoing and evoked electrical activities of the ciliary nerve (Figure  3A ) were recorded at day 21 post-surgery using a multi-unit extracellular recording in ex vivo eye preparations from sham and DED animals. First, we analyzed the spontaneous nerve activities while perfusing the cornea with For statistical analysis, the Kolmogorov-Smirnov test was performed followed by a nonparametric Mann-Whitney using GraphPad Prism version 7. 00 (GraphPad Software, La Jolla, CA, USA).
78 ± 5. 57 imp/sec vs. DED + M8-B (20 µM) 66. 00 ± 11. 43 imp/sec, p < 0. 05; Figure  4A ). When the temperature of the superfusion medium was decreased to 20 • C, the cold-evoked nerve activities reduced by 35. 33% in DED mice chronically instilled with M8-B (20 µM) compared to DED mice instilled with PBS. (DED + PBS 127. 71 ± 13. 53 imp/sec vs. DED + M8-B (20 µM) 82. 33 ± 4. 27 imp/sec, p < 0. 05; Figure  4B ). Results are expressed as mean ± SEM. For statistical analysis, the Kolmogorov-Smirnov test was performed followed by a parametric t-test using GraphPad Prism version 7. 00 (GraphPad Software, La Jolla, CA, USA).
Moreover, we evaluated corneal epithelial damage using slit lamp examinations, after instillation a drop of 0. 5% fluorescein, and observed superficial punctate keratitis (red arrows, Figure  7C ) in the cornea of the DED mice chronically treated with M8-B (20 µM) or PBS. However, the fluorescein staining score was not significantly different between DED groups (DED + PBS 2. 61 ± 0. 22 vs. DED + M8-B (20 µM) 2. 62 ± 1. 16, p > 0. 05; Figure  7C ). Results are expressed as mean ± SEM. For statistical analysis, the Kolmogorov-Smirnov test was performed followed by a parametric t-test using GraphPad Prism version 7. 00 (GraphPad Software, La Jolla, CA, USA).
Spontaneous Pain: Eye Closing Ratio Measurement Spontaneous eye closure is an accurate index used for monitoring spontaneous eye pain  [41]  and is one of the quantitative measures of the grimace scale, which is used to monitor spontaneous pain behavior  [69, 70]. The eye closing ratio was calculated based on photographs of awake and unconstrained mice and corresponds to the height/width ratio of palpebral closure. Width is the distance between the internal and external canthus and height is the distance between the edge of the upper and lower eyelids, going through the center of the cornea. Images were captured by a digital camera using EyeSuite™ software (Bern, Switzerland).
Fluorescein Staining Score The corneas of lightly anesthetized mice were washed with sterile 0. 9% NaCl. Then a drop of fluorescein (Fluorescein Faure 0. 5%) was placed into the conjunctival sac of the right eye. Ocular surface staining was then evaluated using a slit lamp under a cobalt blue light (peak of approximately 400 nm). Images were captured by a digital camera using EyeSuite™ software (Koeniz, Switzerland). The extent of corneal damage (width and intensity of fluorescein take-up area) was scored according to the following scale: 0, absence of staining; 0. 5, slight punctate staining; 1, diffuse punctate staining; 2, diffuse staining covering less than one third of the cornea; 3, diffuse staining covering more than one third of the cornea; and 4, staining covering more than two thirds of the cornea  [41, 71].
Statistical Analyses The data obtained in different groups were compared using the appropriate paired parametric or nonparametric statistical test, as indicated. For statistical analysis, the Kolmogorov-Smirnov test was performed, followed by the parametric t-test or nonparametric Mann-Whitney or parametric one-way ANOVA test (GraphPad Software, La Jolla, CA, USA). All p-values were considered statistically significant when values were <0. 05. All results are presented as the mean ± standard error of the mean (SEM).
5% Fluorescein Faure) in the right eye of the animals. The punctuate keratitis (red arrows) was quantified using standard grading scale, 21 days after surgery in DED mice treated with M-8B (20 µM) vs. PBS (n = 6-9). All tests were conducted at day 21. * p < 0. 05 and ** p < 0. 01 relative to DED mice treated with PBS. Results are expressed as mean ± SEM. For statistical analysis, the Kolmogorov-Smirnov test was performed followed by a parametric t-test using GraphPad Prism version 7. 00 (GraphPad Software, La Jolla, CA, USA).
Contributions: D. F. performed the experiments, analyzed and interpreted the data, generated the figures, discussed the results, and wrote the manuscript. C. B. interpreted the data, discussed the results and their significance, and commented on the manuscript. S. M. P. and A. R. -L. G. designed and supervised all experiments, interpreted the data, discussed the results and their significance, and wrote the manuscript. All authors approved the final article. All authors have read and agreed to the published version of the manuscript. Funding: This work was funded by Laboratoire Théa, within the framework of research collaboration with Sorbonne Université/Institut de la Vision. Darine Fakih is supported by the Association Nationale de la Recherche et de la Technologie (Conventions Industrielles de Formation par la Recherche N • 2016/1641).
(C) Cornea alteration was examined using a slit-lamp microscope with a cobalt blue filter after placing a drop of fluorescein (0. 5% Fluorescein Faure) in the right eye of the animals. The punctuate keratitis (red arrows) was quantified using standard grading scale, 21 days after surgery in DED mice treated with M-8B (20 µM) vs. PBS (n = 6-9). All tests were conducted at day 21. * p < 0. 05 and ** p < 0. 01 relative to DED mice treated with PBS. Results are expressed as mean ± SEM. For statistical analysis, the Kolmogorov-Smirnov test was performed followed by a parametric t-test using GraphPad Prism version 7. 00 (GraphPad Software, La Jolla, CA, USA).
Author Contributions: D. F. performed the experiments, analyzed and interpreted the data, generated the figures, discussed the results, and wrote the manuscript. C. B. interpreted the data, discussed the results and their significance, and commented on the manuscript. S. M. P. and A. R. -L. G. designed and supervised all experiments, interpreted the data, discussed the results and their significance, and wrote the manuscript. All authors approved the final article. All authors have read and agreed to the published version of the manuscript. Funding: This work was funded by Laboratoire Théa, within the framework of research collaboration with Sorbonne Université/Institut de la Vision. Darine Fakih is supported by the Association Nationale de la Recherche et de la Technologie (Conventions Industrielles de Formation par la Recherche N • 2016/1641).