dataesr/scientific-paragraphs-categorization huggingface dataset:
Study population We used data from the ongoing Whitehall II cohort study. Briefly, 10,308 male and female London-based civil servants, aged 35-55 years, were recruited to the study in 1985, with a response rate of 73% Fig. 1. Cohort flowchart. (Marmot et al. , 1991). Participants have since been followed up with questionnaire surveys and clinical examinations every 4-5 years. Written informed consent was obtained from all participants at each follow-up clinical examination. The flow diagram indicates the study selection process (Fig. 1 ). Eligibility for the present study required continued participation from the time when salivary cortisol was collected in  2007-2009 (n = 6225). Of those eligible, 4172 respondents provided six completed cortisol measures, completed the logbook and sample times, were not taking corticosteroid medications, and took their first saliva sample within 15 min of waking based on the protocol for cortisol sample collection.
Acknowledgments We thank all of the participating civil service departments and their welfare, personnel, and establishment officers; the  British Occupational Health  and Safety Agency; the  British Council of Civil Service Unions ; all participating civil servants in the Whitehall II study; and all members of the Whitehall II study team. The Whitehall II Study team comprises research scientists, statisticians, study coordinators, nurses, data managers, administrative assistants, and data entry staff, who made this study possible.
e. skewed) datasets did not overestimate or underestimate the treatment effect. In HARMONY CTP, geometric mean WRC during the 4-week stable dosing period (adjusted for baseline differences) was significantly lower for pitolisant (baseline, 9. 1; final, 2. 3) compared with placebo (baseline, 7. 3; final, 4. 5)  [39, 50]. During the stable dose period, the frequency of cataplexy attacks in the pitolisant group was approximately half that in the placebo group (rate ratio, 0. 51; 95% CI, 0. 44-0. 60; P < 0. 001). In the geometric mean analysis for HARMONY 1, the analysis population included patients with a history of cataplexy, regardless of whether cataplexy was observed during the baseline period (pitolisant, n = 25; placebo, n = 24) and the frequency of cataplexy was calculated as the daily rate, rather than the weekly rate  [39].
SEM, standard error of the mean. **P< 0. 01 vs placebo. Reprinted from  [54] , via Creative Commons BY-NC-ND license (http://creativecommons. org/licenses/by-nc-nd/4. 0/). study enrollment, as is common in studies of narcolepsy, including pivotal trials for sodium oxybate  [55]  and calcium, magnesium, potassium, and sodium oxybates  [56]. The frequency of cataplexy attacks was assessed using only subjective measures (i. e. patient diaries), which is consistent with the ongoing lack of an objective method for evaluating the frequency and severity of cataplexy episodes. Because these clinical trials were sponsored by the pharmaceutical company that developed pitolisant, the need for additional, independent data is also important.
Oral administration of a hypocretin-2 receptor selective agonist (TAK-944) increased wakefulness and suppressed cataplexy-like episodes in mouse models of narcolepsy  [66] , and phase 2 studies in patients with narcolepsy are ongoing (NCT04096560, NCT04820842). Other potential hypocretin-based approaches include gene therapy, hypocretin neuronal transplantation, and stem cell transplantation  [63, 67]. Much additional research is needed to determine the feasibility, efficacy, and safety of hypocretin-based therapies in the treatment of narcolepsy. At this time, the H 3 receptor antagonist/inverse agonist pitolisant and the GABA B agonist oxybate compounds are the only available treatments for NT1 that have demonstrated efficacy for the reduction of both EDS and cataplexy  [20]. There remains a need to improve the recognition and assessment of cataplexy; potential options for addressing this issue could include expert consensus recommendations and the development of better measures for use in research and clinical practice.
Clinical assessment At study entry, all patients underwent a neurological examination and were scored using the Expanded Disability Status Scale  22  (EDSS). For each patient, the EDSS score 2 years before study entry was retrospectively collected through the careful revision of primary medical files, and checked for consistency using our local database entered in the European Database for Multiple Sclerosis records. Disability worsening over 2 years was evaluated as changes in EDSS between the inclusion visit and 2 years before study entry, and converted into EDSS step change  23. EDSS step change was used to classify patients as clinically worsening (EDSS step change ≥ 0. 5) or clinically stable over the 2 years preceding study entry. Patients were classified as untreated (off, if they had no disease modifying treatment during this period) or treated (on, if they received a disease modifying treatment) (Table  1  and SuppTable1;Data available from Dryad https://doi.
Anatomical images processing and generation of periventricular concentric rings Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. In patients, T2 hyperintense lesions were manually contoured by an expert investigator (GB) on T2-weighted scans with reference to FLAIR sequences using a semi-automated edge-finding tool (JIM v6. 0, Xinapse systems, Essex, UK). The corresponding lesion masks were generated and aligned to the individual T1-weighted scans using FLIRT (FMRIB's [Oxford Centre for Functional MRI of the Brain's] Linear Image Registration Tool, FMRIB Software Library, version 5. 0. 9)  26. After "lesion-filling" procedure in patients only  27  , T1-weighted were segmented using a multi-atlas segmentation approach 28 , and analyzed with Freesurfer (version 6.
Compared to the white matter of HC, patients with multiple sclerosis showed a higher percentage of DPA+ voxels at the closest proximity to the ventricles and a steeper slope in both normal-appearing white matter (intercept: 37. 0±16. 5%, t=4. 70, p=1. 83e-5; slope: -0. 67±0. 54%. mm -  , t=-3. 19, p=2. 37e-3) and T2 lesions (intercept: 53. 3±21. 9%, t=6. 50, p=5. 09e-8; slope: -0. 78±0. 72%. mm -  , t=-2. 49, p=0. 018) (Table2). Moreover, in the normal-appearing white matter of patients with multiple sclerosis, the percentage of DPA+ voxels was found to be associated not only with the distance from ventricles, but also with the percentage of lesional voxels in each periventricular ring (t=-5. 59, p=1. 64e-6; t=6. 63, p=1. 00e-10; respectively). When we performed the patient subgroup analysis, while the PMS patients showed a higher level of innate immune cell activation in the periventricular white matter, normalappearing white matter and T2-lesions, and steeper slopes compared to RRMS, these differences were not statistically significant (Table  2 , Supplemental Table2; Data available from Dryad https://doi.
Acknowledgements We thank the  Centre d'Investigation Clinique team  from  ICM ,  Céline Louapre ,  Jean-Christophe Corvol  for protocol organization,  Caroline Papeix ,  Catherine Lubetzki ,  Elizabeth Maillart ,  Rana Assouad  for helpful discussion and clinical help,  C Baron ,  C Manciot ,  Vincent Lebon  (SHFJ, CEA),  Geraldine Gourbil  ( CIC ) for their invaluable assistance. We address special thanks to  Mattia Veronese ,  Federico Turkheimer  for technical help and fruitful discussions. We also thank the staff of the CENIR (Research neuroimaging unit of the ICM), and the staff of the  Unité de Recherche Clinique of Pitié Salpêtrière , in particular  Anne Bissery  and  Laura Morizot.
Methods Study design. A retrospective analysis of a consecutive series was conducted. Screened patients had undergone surgical resection of a diffuse glioma under awake condition in a single center between January 2013 and January 2020. All patients were operated on by the same neurosurgeon (H. D). It should be noted that the data presented in this study were gained in a clinical context, and that the protocol described below reflects our standard clinical approach. Approval for the study and its methods was granted by the Institutional Review Board of Montpellier University Medical Center (N°202000557). All patients gave their informed consent prior to inclusion. All methods of this study were performed in compliance with the tenets of the Declaration of Helsinki. Data and imaging were studied following anonymization in agreement with the Personal Data Protection Act and the code of conduct for responsible use of Human Tissue and Medical Research.
Such dissociations at the RME/SCI tasks occurred when patients produced correct responses to the RME but reported a low level of self-confidence (≤ 2/6) and when patients produced incorrect responses but maintained a high level of self-confidence (≥ 5/6). Preoperative neuropsychological assessment. Patients received a neuropsychological assessment, as part of their routine preoperative care. Scores were appropriately converted into Z-scores based on published French normative data (adjusted for educational level, age and sex). As some patients were not native Frenchspeakers, they did not receive a full neuropsychological examination. Note that some neuropsychological tasks were tailored to the location of the tumor and, therefore, were not administered to all patients (e. g. the reading task was uniquely administered to right-handed patients with a left-sided tumor).
Imaging acquisition and normalization. MRI acquisition (3 T, Siemens Avento, Siemens Medical Systems) was performed for all patients the day before surgery and 3 months after surgery, including Fluid-attenuated inversion recovery (FLAIR) sequences and T1-weighted 3D Gadolinium-enhanced sequences. The tumor volume was measured with a dedicated software (Myrian, Intrasense, Montpellier, France). All 3-month postoperative MRI datasets were conformed to the standardized Montreal Neurological Institute (MNI) space, using SPM12 implemented in MATLAB environment (Release 2018a, The MathWorks Inc. , Natick, NA, USA). All normalized MRIs were carefully checked to identify maladjusted deformations. Spatial topography of stimulations. Functional sites of interest were plotted in the MNI space using operative reports and intraoperative photographs.
Disconnectome analysis. In order to define with matter pathways involved in self-evaluative processing, the disconnectome MAPS software was used, as part of the BCBToolkit  45. For a given stimulation, Disconnectome MAPS provides a probability to be disconnected for every voxel of the MNI152 template, based on a tractography-based atlas of white matter  46. A threshold of 0. 00 was applied in the BCBToolKit command, meaning that all interindividual variation in the topological positioning of the tracts were considered. Given the spatial distribution of the responsive DES, individual disconnectome maps were overlaid in MRICroGL software with the third version of the automated anatomical labelling atlas (AAL3) and the Human Connectome Project (HCP) tractography database to extract voxels with maximal probability of disconnection (p max ) and their corresponding MNI coordinates for each region of interest.
5% for induction, 1. 5% during set-up) and a bolus of 0. 025 mg/kg dexmedetomidine was given by intraperitonial injection. Isoflurane was discontinued after 5 min. Continuous subcutaneous infusion of dexmedetomidine at a dose of 0. 05 mg/kg/h was started 10 min after the bolus injection. While under anesthesia, body temperature was monitored through a rectal probe and maintained at 37. 0 AE 0. 5 C using a warm water pad. Respiratory rate was between 262-293 breaths per minute while awake and between 142-158 breaths per minute while anesthetized. MRI data were acquired with a Bruker BioSpec 9. 4 T scanner, using an 86-mm volume coil (Bruker) for transmit and a 4-channel phased-array cryogenic mouse head coil (Bruker) for receive. After a Localizer scan for animal positioning, T 2 RARE anatomical images were acquired (TE 33 ms, TR 3300 ms, FOV 16 Â 16 mm, matrix size 256 Â 256, slice thickness 0.
Data processing Data were preprocessed using custom-written scripts in MATLAB and SPM12 (http://www. fil. ion. ucl. ac. uk/ spm/). After the pCASL images were converted from Bruker format to NIFTI format, the mouse brain was extracted manually using ITK-SNAP (http://www. itks nap. org/), realigned for motion correction, normalized to a mouse brain template  74  (http://imaging. org. au/ AMBMC/Model), and spatially smoothed (0. 4 mm isotropic Gaussian Kernel) for quantifying CBF. 41 he T 2 * and T 2 maps were calculated using the normalized magnitude multi-echo MGE and MSME data with a mono-exponential fit by using the Levenberg-Marquardt algorithm. R 2 0 images were calculated using E2. 14 o test data normality, we used Kolmogorov-Smirnov (KS) tests. The Lilliefors adjustment was used where N 15.
Most results are presented pervoxel (each voxel averaged across all mice) to follow previous studies of CMR O2 in humans. 42 In addition to per-voxel results, per-mouse results were also calculated. In per-mouse results, to test statistical significance in maps of CBF and R 2 , the mean value of the map for each mouse was taken in 15 different brain regions (see Table  S1 ). A two-tailed, paired T-test was done for each region, counting each mouse as a sample and pairing awake vs. anesthetized in that mouse. Resulting p values were corrected for multiple comparisons using Sequential Goodness of Fit 43 at p 0. 05, considering each brain map as a statistical family with 15 tests within it. b maps were calculated using a previously published method  26  in MATLAB. By measuring R 2 0 as a function of the contrast agent concentration, b was experimentally determined on a voxel-by-voxel basis.
A per-voxel rcfMRI was calculated from E4 using maps of R 2 0 from each state, maps of CBF from each state, a ¼ 0. 2, and the b map calculated from a separate cohort of mice. All results were normalized to the template described above. For further analysis, after registration, only slices 5-16 were selected due to image distortion induced by the head holder. A manual mask was applied to the final result by using the roi_poly function on each slice in MATLAB to exclude any artifacts along the edge of the brain. This helped maintain assumptions of our model by avoiding the higher inhomogeneity of the static magnetic field (B 0 ) at the edge of the brain. In addition, only the 5th through 16th slices were used for analysis, to avoid possible B 0 inhomogeneity at the far rostral and caudal extents of the brain.
) This resulted in removal of one mouse, leaving N ¼ 14. The comparison analysis included both a test based on linear similarity, Pearson correlation, and a test which can also find non-linear similarities, mutual information (base 2 for logarithms, 5 bins of values), to compare rCMR O2 _T and rCMR O2 _M. Statistical significance for Pearson correlation was calculated using the permutation test from the built-in corr function in MATLAB. Statistical significance for mutual information was calculated by randomly permuting which mouse's rCMR O2 _T corresponded to which mouse's rCMR O2 _M and calculating mutual information between them for 100,000 random permutations. A one-tailed p value was calculated using the distribution of the randomized data to calculate a percentile, assuming the mutual information of the actual data was greater than the randomized data.
Figure1. Summary of the overall method for rcfMRI. Data were recorded in the awake and anesthetized states using the same MRI sequences. The relaxation time map R 2 0 was calculated based on R 2 and R 2 *, and combined with CBF in both states to calculate rCMR O2 in the awake divided by the anesthetized state. rCMR O2 was calculated using a range of values for the a constant, and a pervoxel map of the b constant which was measured experimentally. Global CMR O2 (gCMR O2 ) was calculated from this method (rCMR O2 _M), and also from TRUST MRI sequences by converting the T 2 measured with TRUST to venous oxygen saturation Y v (rCMR O2 _T).
Funding The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The authors acknowledge financial support from  ShanghaiTech University , the  Shanghai Municipal Government , and the  National Natural Science Foundation of China  Grant  81950410637  (GJT) and Grant  81771821  (ZL),  Strategic Priority Research Program  of the  Chinese Academy of Sciences  (Grant No. XDB32030100  to ZL), the  Shanghai Municipal Science and Technology Major Project  (Grant No. 2018SHZDZX05  to ZL) and  CAS Pioneer Hundred Talents Program  (to ZL). Peter Herman  and  Fahmeed Hyder at Yale University  were supported by  R01 NS-100106 ,  R01 MH-111424 , and  R01 DC-014723-05S1  from  NIH. The funding sources did not contribute to the writing of this manuscript.
mRNA Expression of Ectonucleotidases and Nucleotide Receptors in Mouse Bladder Smooth Muscle Layer The data from Figure  4  suggest the implication of nucleotide receptors in these effects where the ectonucleotidase NTPDase1 plays a central role in the modulation of the process. We then measured the expression of these potential actors by RT-qPCR. First, we quantified Krt7 (a marker of epithelial cells) and Myh11 (a marker of SMCs) in our smooth muscle samples. As seen in Figure  6A , mRNA levels of Krt7 were negligible when compared to Myh11 for both sexes and both genotypes, demonstrating that the preparation of smooth muscles is exempt of epithelial cells. It is noteworthy that we perfused the animals before sacrifice to avoid blood cell contamination. We then quantified the expression of ectonucleotidases, as well as of the nucleotide receptors and of the adenosine receptors to find the potential receptor(s) involved in the contractile response to nucleotides.
This implies that P2Y 2 and/or P2Y 4 were also responsible for part of this contraction as both receptors are also activated by UTP. Therefore, these data suggest the implication of P2Y 6 in the responses to UDP and that UTP activate contractions via P2Y 6 as well as via other P2 receptors (P2Y 2 and/or P2Y 4 ). Strips from male bladders contracted significantly more in the presence of the thromboxane analogue (U46619) when compared to females in both genotypes (WT and P2rY6 -/-). Gene expression profile in male and female bladder SMCs. SMCs were separated from the epithelial layer as mentioned in the "Materials and Methods" section. RNA was isolated from the SMC layer and the expression of the epithelial cell marker Krt7 and the SMC marker Myh11 (A), P2Y receptors (B), P2X receptors (C), ectonucleotidases (D), and P1 receptors (E) were quantified by RT-qPCR.
Figure5. Gene expression profile in male and female bladder SMCs. SMCs were separated from the epithelial layer as mentioned in the "Materials and Methods" section. RNA was isolated from the SMC layer and the expression of the epithelial cell marker Krt7 and the SMC marker Myh11 (A), P2Y receptors (B), P2X receptors (C), ectonucleotidases (D), and P1 receptors (E) were quantified by RT-qPCR. Data are normalized to GAPDH (glyceraldehyde 3-phosphate dehydrogenase; left panels) and ACTB (actin beta; right panels) mRNA level. Entpd1 +/+ : wild type mice. Entpd1 -/-: NTPDase1 deficient mice. Data presented are the means ± SEM of three independent experiments in duplicate each with SMCs pooled from three mice.
A tion, we performed snRNAseq on regenerated adult legs approximately 2 and 6 months following amputation (see Suppl. Figure  S7 ). To account for genetic, environmental and physiological (e. g. nutritional, circadian, molt-or age-related) effects on the nuclear transcriptomes, we compared snRNA data from regenerated legs (8,925 and 6,668 nuclei from 2 and 6 months post amputation, respectively) with data from contralateral uninjured legs collected simultaneously from the same individuals (8,539 and 7,370 nuclei) (Figure  4A ). The analysis was performed de novo on the integrated datasets, projecting the data on a new UMAP (Figure  4A-C ). In both experiments, the regenerated legs have the same cell clusters as their contralateral controls, including all the clusters corresponding to the major identified cell types, the minor clusters, and those corresponding to yet unidentified cell types (Figure  4B-D ).
The images shown in Figure  1A , 1C and S3 were cropped manually and placed on a black background. Colour highlights in Figures  1  and S3  were added as separate layers using the overlay channel option Adobe Photoshop CS6. Testing mechanosensory function. Large adult males were immobilized on standard 60mm Petri dishes from their body using surgical glue (as described in  (Alwes et al. , 2016) ). The setae on T4 and T5 legs were stimulated using a minutien pin (Fine Science Tools, #26002-10) and the animals' whole-body response was recorded (Suppl. Video S1 and Data S2). Two rounds of experiments were performed under dim light; in the first round, the posterior comb setae of the carpus were stimulated twice (n=22 individuals). After each stimulus the response was recorded and the animals were left to relax for 15 minutes.
After washing overnight in PTx at 4˚C, the samples were incubated with the secondary antibody (anti-mouse IgG Alexa 488, diluted 1:1000; Life Technologies A11001, RRID: AB_2534069) in PTxD+ for 3 days at 4˚C. Samples were then washed overnight in PTx at 4˚C and mounted in Vectashield mounting medium (Vector Labs, H-1000). The samples were imaged on a Zeiss LSM 800 laser scanning confocal microscope. Nuclear isolation and sequencing. For each snRNAseq dataset we collected a pool of 12-16 thoracic T4 and T5 legs from large adult males. The smallest specimens had a body length of ~9 mm (estimated age >12 months) and the average had a body length of ~11 mm (estimated age >18 months). The legs were amputated at the proximal end of the basis (excluding the gills and the coxal plates) using a microsurgical knife (Electron Microscopy Sciences, #72047-30) under anaesthesia in 0.
Reads were mapped to the P. hawaiensis genome version Phaw_5. 0 (see below) using the Cell Ranger Software Suite 6. 0. 1 (10x Genomics;  (Zheng et al. , 2017) ). Cell Ranger output included lists of features, barcodes and matrices (corresponding to putative genes, cells and read counts, respectively). Subsequent analyses were performed using the R package Seurat v4  (Hao et al. , 2021). Quality checks are shown in Figure  S14.
Genome annotation. The snRNAseq reads were mapped on the Parhyale hawaiensis genome assembly Phaw_5. 0 (https://www. ncbi. nlm. nih. gov/assembly/GCA_001587735. 2/), in which 19 poorly assembled mitochondrial scaffolds were removed and replaced by the publicly available complete mitochondrial genome (RefSeq NC_039402. 1). To assign reads to genes we used the gene annotation described in Sinigaglia et al. (Sinigaglia et al. , 2021). Many genes in this annotation were of undefined or incorrect strandedness. We defined the correct gene strandedness using information from our snRNAseq data (stranded reads from all five snRNAseq experiments) or by identifying putative coding sequences through sequence similarity. First, we compared the total number of snRNAseq reads mapping to opposite strands per gene model.