dataesr/scientific-paragraphs-categorization huggingface dataset:
Hybridization In situ hybridization was performed as described previously  [13]. Specific antisens oligonucleotide probe for POMC and NPY were used as described previously  [13, 14]. Probes were labeled with 35S-adATP using terminal deoxynucleotidyl transferase. After hybridization, the brain sections were dehydrated and coated with liquid photographic emulsion (Kodak NTB-2). They were processed after 7 days of exposure. Semi-quantitative analysis of hybridization signal was carried out on nuclear emulsion-dipped slides over the confines of reactive cells in the ARC of the hypothalamus using Zeiss Optical System coupled with a computer and Mercator Image Software (PRIMACEN platform). The optical density (OD) of the hybridization signal was measured under dark-field illumination at 10× magnification.
Sections from control and treated animals were matched for rostrocaudal level. The hypothalamus was digitized and subjected to densitometric analysis with ImageJ software (version 1. 44p, NIH, USA), yielding measurements of integrated OD. The OD of each specific region was then corrected for the average background signal, which was determined by sampling tissues immediately outside the cell group of interest. The operator was blinded to the anesthetic drug used in each group.
Statistical analysis In the in situ hybridization study, quantitative data are presented as mean values with a confidence interval of 95%. Comparison of mRNA levels between experimental groups was performed by analysis of variance (ANOVA) followed by Dunnett's multiple comparison test. In oral food intake measurements, data are presented as mean values with a confidence interval of 95%. Comparisons of duration of anesthesia and ingestat were performed by Kruskal-Wallis test followed by Dunn's multiple comparison test. Each analysis was performed with GraphPad Prism v6. 0 software (La Jolla California USA). For both analyses, comparisons were performed between NaCl 0. 9% control and anesthetics. P < 0. 05 was considered statistically significant.
Despite these interesting results, transposition to humans, especially in a surgical context, is difficult. Indeed, anesthesia in surgical context is not limited to the use of a single anesthetic but to a combination, inducing complex and combined effects on many physiological variables, and therefore probably on the feeding behavior. In addition, surgical stress and pain are identified as altering the feeling of hunger. If our work does not provide full certainty on the choice of anesthetic, it deepens our understanding of the effects of gabaergic drugs on the complex system of food intake and opens up therapeutic possibilities for post-operative rehabilitation. Thus, we are awaiting the results of a randomized controlled study on the effects of propofol versus sevoflurane on post-operative feeling of hunger, which may provide additional elements of response (NCT02272166).
RESULTS Hopx Is Enriched in NSCs of the dSVZ and in Cells of the Astrocytic Lineage In a previous study, we examined the transcriptome of spatially distinct domains of the postnatal SVZ and revealed differential transcriptional networks in region-specific NSCs  (Azim et al. , 2015). This heterogeneity was explored further by analysis of TFs and transcriptional regulators (termed hereafter as TFs) as well as their association with defined neural lineages. Focusing on TFs only, 112 were differentially expressed between the regionalized subpopulations of NSCs (dNSCs: 61; lNSCs: 51; Figures  1A  and S1A-S1C ). The expression of TFs enriched dorsally was confirmed by examining in situ databases (http://www. brain-map. org/), and by immunohistochemistry (Figures  1C  and 1D ). Among transcripts enriched in dNSCs (Figure  1B ), 5 out of the top 10 (NeuroD6, Eomes, NeuroD1, Tbr1, Neurog2) are known major determinants of the glutamatergic neuronal lineage  (Schuurmans et al.
, 2004; Hevner et al. , 2006; Brill et al. , 2009; Winpenny et al. , 2011). In addition, a meta-analysis was performed on publicly available datasets of isolated glial cells and neurons for the characterization of TFs into defined neural lineages  (Cahoy et al. , 2008). Interestingly, this analysis revealed that TFs enriched in dNSCs formed at least three clusters corresponding to astroglia (18/61), neurons (15/61), and oligodendroglia (11/61; Figure  1E ). In contrast, lNSCs enriched TFs identified a single large neuronal cluster (42/51), while those of oligodendroglia were relatively fewer (3/51) and the astroglial cluster was absent (Figure  S1E ). These observations underline the greater diversity of lineages arising from the dSVZ, whereas the lSVZ generates almost exclusively interneurons (reviewed in  Fiorelli et al.
We selected known transcripts enriched in NSCs as well as in defined neural lineages  (Azim et al. , 2015; Cahoy et al. , 2008)  and compared their expression levels by qPCR. Measured transcripts were all enriched in NSCs compared with the dSVZ, thereby validating our fluorescence-activated cell sorting strategy. In addition, there was no overall regional enrichment of stem cell markers (Hes5, Egfp;  Basak and Taylor, 2007)  and a proliferation marker (Pcna) within the different NSC populations, although the neuroblast marker Dcx was enriched in lNSCs, consistent with a greater number of neuroblasts generated by this SVZ microdomain  (Yang et al. , 2004; Figure 3A, top panel). Markers for the astroglial, oligodendroglial, and neuronal lineages were confirmed using the transcriptional datasets from the Barres group  (Cahoy et al.
, 2015; Azim et al. , 2016). NSCs located in SVZ microdomains originate from specific regions of the developing forebrain  (Fuentealba et al. , 2015) , and generate a large diversity of neural cells, including neuronal subtypes, depending on the expression of particular transcriptional programs. Consequently, the expression of TFs directly correlates with the acquisition of defined neural fates, a concept that was explored in the present study. We took advantage of the whole-genome transcriptome of region-specific postnatal NSCs that were recently resolved  (Azim et al. , 2015). A meta-analysis of TFs expressed in dorsal and lateral NSCs with datasets of isolated forebrain neuronal and glial subpopulations  (Cahoy et al. , 2008)  highlighted transcriptional networks that correspond to microdomain-specific NSCderived lineages.
Meta-Analysis of Transcriptional Profiles To generate the lists of TFs that are enriched in dNSCs and lNSCs, we made use of previously published datasets  (Azim et al. , 2015; Cahoy et al. , 2008) , accessible on the Gene Expression Omnibus database (GEO: GSE60905 and GSE9566) and followed a procedure detailed in Supplemental Experimental Procedures.
Quantifications and Statistics Images were acquired using a Leica DM5500 epifluorescent microscope, a Leica TCS SPE II, and a TCS SP5 confocal microscope (Leica Microsystems, Wetzlar, Germany). Images were quantified using ImageJ-win64 or assembled as representative pictures with LAS X, ImageJ, and Photoshop (CS4). Statistical analysis was done with Microsoft Excel 2013 and GraphPad Prism 7. All data are shown as mean ± SEM and statistical significance was calculated using the unpaired t test (in figures *p < 0. 05, **p < 0. 01, ***p < 0. 001, ****p < 0. 0001).
ACKNOWLEDGMENTS The authors would like to thank  Jonathan A. Epstein  for kindly sharing the HOPX CreERT2 mouse line,  Verdon Taylor  for sharing the HES5:EGFP mouse line, and  Daniel Hohl  for sharing the HOPX LacZ/WT knockin mouse line. Furthermore, we would like to thank  Xavier Morin ,  Colette Dehay  and  Laura Lόpez-Mascaraque  for providing plasmids for these experiments. We are grateful to  Bruno Fischer  and  Anahi Hurtado-Chong  for their technical assistance and  Vanessa Donega  for critical reading of the manuscript. This study was supported by a grant from the '' Programme Avenir Lyon Saint-Etienne '' and S. Z. was further supported by a  Doc. Mobility fellowship  from the  Swiss National Science Foundation  (SNF; grant number  P1SKP3_168418 ). Other support was received from an  SNF  project grant  NRP63  to O.
Our efforts provide a high-resolution, open-access dataset for the community by comparing our functional map of the hindbrain to existing open-access atlases and enabling further investigation of this population's role in locomotion. When exploring their environments, animals constantly perform updates based on their motor actions and available sensory information. In the larval zebrafish, which swim via discrete bouts of tail oscillation 1 , there is still much to learn about the neural circuits which integrate sensory information from the outside world with proprioception, and signal to initiate locomotion. A great challenge in the study of motor control has been the technical difficulty of recording activity from neurons responsible for motor actions, in the midst of active motor actions.
Thus, there is still much left unexplored. Here we ask which neurons responsible for motor commands and sensorimotor processing are located in or near the zebrafish hindbrain. We use population calcium imaging to record from the brains of actively swimming but restrained larval zebrafish in an attempt to incorporate multisensory signals into our dataset. Since such information processing may incorporate both excitatory and inhibitory cell types, we then ask if these active populations are inhibitory by mapping them onto known transgenic lines in the ZBB atlas  3, 4.
We therefore calculated the pixel-wise correlation of each cluster mean during each swim event (for swim cluster 1) and each stimulus presentation (for stimulus clusters 1-3). To compare activity related to each cluster between larvae and brain regions, we registered the resulting average correlation maps for all 10 larvae to a common reference brain. Using Tg(vglut2a:DsRed) expression as a bridge, we registered our dataset with the ZBB brain atlas  3, 4. Once this bridge was established, we were able to easily compare the pixels associated with the clusters identified above with the transgenic lines available in the ZBB atlas. We found considerable spatial overlap between regions that correlate with the swim cluster and the images of the Tg(glyt2:mCherry) line from our own dataset, and also with the images of the Tg(glyt2:GFP) line in the ZBB atlas, indicating activation of glycinergic cells during swimming (Fig.
Discussion Our study provides the community with an open-access, single cell-resolution population imaging dataset of hindbrain calcium activity during active locomotion induced by optomotor stimuli. Here we investigated which inhibitory neurons are recruited during sensorimotor integration and found interesting responses in diverse populations of glycinergic and GABAergic neurons whose activity correlates with motor generation and/or visual integration. In order to identify the neurotransmitter phenotypes of functional clusters, we relied on the combination of transgenics as well as the use of the recent creation of open-access zebrafish larval brain atlases by several groups  [2] [3] [4] 32. The e larval brain atlases have enabled the integration of functional datasets with anatomical markers, in both fixed and live brains.
Additionally, transgenic Tg(vglut2a:loxP-DsRed-loxP-GFP)  6  larvae referred to as Tg(vglut2a:DsRed) were used for comparing and bridging datasets. Calcium imaging and behavior setup. Double transgenic Tg(HuC:GCaMP5G; glyt2:mCherry) larvae were mounted in glass-bottom dishes (MatTek, Ashland, MA, USA) filled with 1. 5% low-melting point agarose, and the agarose surrounding the tail was removed. Calcium imaging was performed on a two-photon microscope (2p-vivo, Intelligent Imaging Innovations, Inc. , Denver, CO, USA) including a Mai Tai Deepsee laser (Spectra-Physics) tuned to 980 nm and a Zeiss Axio-Examiner Z1 with a Zeiss W Plan-APO 20X water-immersion objective. Fluorescent images were acquired using Slidebook software (3i Intelligent Imaging Innovations, Inc. , Denver, CO, USA) at 5. 81 Hz with 1.
Infrared light from the imaging laser was blocked with a filter located in front of the camera. Calcium imaging, behavior, and stimulus presentation were synchronized via a Digidata series 1322 A digitizer, and pClamp 8. 2 software (Molecular Devices-Axon Instruments, Sunnyvale, CA, USA). After each experiment, the larva was anesthetized with MS-222 and a high-resolution Z-stack was recorded with 1 µm z-step for both red (mCherry) and green (GCaMP5G) channels simultaneously. Parameters were: 1024 × 499-1024 pixels, 10 pixel averaging, 3-5 frame averaging, 4-8 µs dwell time per pixel.
Analysis of behavioral videos and bout extraction. Using custom MATLAB software (Mathworks, Natick, MA, USA), 8 segments of the tail were extracted between manually chosen points at the end of the swim bladder and the tip of the tail  19, 57, 58. From the tail-bend angle over time, we detected local maxima and minima from which bout and interbout durations were extracted. All bouts were visually inspected by experimenters and bouts were manually excluded from the dataset in cases of tracking failures, or when belonging to obvious escape or struggle behavior. Bouts were not further subdivided or categorized for this analysis. All custom MATLAB scripts are available upon request.
6 with their stimulus-triggered average and swim-driven when having and average correlation coefficient >0. 6 with their swim-triggered average. Traces with an average correlation coefficient >0. 6 with both their swim-triggered and stimulus-triggered average were considered ambiguous and excluded from the dataset (Supplementary Fig. S1 ). Clustering and anatomical mapping. To identify different clusters of activity within each of these categories, the previously identified average swim-triggered traces and stimulus-triggered traces were then clustered for each category independently. This allowed us to define cluster centroids that correlate either with the occurrence of swim bouts or the presentation of the visual stimulus. Clustering was based on methods published in Bianco et al. , 2015  24, 60  (correlation threshold was 0.
(c) Trials during which a single plane is imaged for 315 s with sequential presentations of moving optomotor stimuli for 10 s in open-loop (grey bars). Larvae initiate locomotion more frequently during the periods of stimulus motion than when the stimulus is stationary. (d) Single image extracted from a high-speed behavioral movie showing the larva under IR illumination with its head embedded in agarose and the tail cut free. Offline tracking of the tail in eight sections between the caudal end of the swim bladder and end of the tail. (e) Tail-bend angle (degrees) defined between the swim bladder and the end of the tail can be plotted and bouts of swimming are automatically extracted (red boxes). Tracking failures and obvious struggles were excluded from the dataset. Example swim bout expanded below (1) and example struggles expanded below (2,3).
Acknowledgements We thank  Professor Shin-Ichi Higashijima  for the Tg(glyt2:mCherry) and Tg(vglut2a:DsRed) lines, and  Professor Florian Engert  for the Tg(HuC: GCaMP5G ) line. We are grateful to  Dr. Ruben Portugues  and  Dr. Isaac Bianco  for useful discussions on the cerebellum and clustering methods, respectively. We thank the company  Intelligent Imaging Innovations  ( 3i ) and  Dr. Osnath Assayag  for technical assistance. We thank  Sophie Nunes-Figueiredo ,  Bogdan Buzurin ,  Natalia Maties , and  Monica Dicu  for excellent animal care. We thank  Dr. Christoph Gebhardt  and the members of the  Wyart lab  (http://wyartlab. org/)for critical feedback on the manuscript. This work was supported mainly by the  ERC Starting Grant  "Optoloco" # 311673 , together with the  Fondation pour la Recherche Médicale (FRM) student fellowship for U.
An excellent review of commercially available BoNT products and their manufacture is provided in Pickett, 2014  [9]. The key aspects of the major BoNT products that are available in the United States and Europe are given in Table  1. Currently, all of the commercially available BoNT products are manufactured using native Clostridium botulinum as the production organism, although some companies are exploring the use of recombinant expression using Escherichia coli. This would allow a standardised and safer manufacturing process for BoNT/A and for other serotypes and genetically modified versions of the neurotoxin. 1st Approval In the United States of America (USA) and Europe, both Dysport ® and Botox ® are approved for use in adult upper and lower limb spasticity, while Xeomin ® is only approved for use in adult upper limb spasticity (the Xeomin adult lower limb Phase 3 pivotal study did not meet its primary endpoint at the 400 U dose [NCT01464307, https://clinicaltrials.
gov/]). Dysport ® is the only BoNT/A product approved in the USA for the use in children with lower limb spasticity. The Botox ® study is still ongoing, (NCT01603628), while the Xeomin ® pivotal Phase 3 study did not meet its primary endpoint (NCT01893411). Over the last two decades, the localized efficacy of BoNT/A, and its well tolerated safety profile, has resulted in significant growth of on-label use across multiple therapeutic and aesthetic indications. BoNT/As are well tolerated, which has also favoured significant growth in its empirical/off-label use in a variety of movement, ophthalmologic, gastrointestinal, urologic, orthopedic, dermatologic, secretory, and pain disorders. BoNT is injected locally in skeletal muscles (on-label such as cervical dystonia, hemifascial spasm, blepharospasm, spasticity in adult and children; or, off-label such as writer cramp, tremors, spasmodic dysphonia), smooth muscles (on-label neurogenic detrusor overactivity, idiopathic bladder overactivity; or, off label such as bladder pain syndrome, detrusor sphincter dyssynergia) or exocrine gland hyperfunction (on-label sialorrhea, axillary hyperhidrosis; or, off-label, such as Frey's syndrome, plantar/palmar hyperhidrosis).
In another study recently completed in 176 patients with OA knee with Botox ® , no statistically significant difference was observed on any of the parameter assessing pain between the onabotulinum toxin and placebo (NCT02230956). Both of the studies add to earlier clinical studies using intra-articular BoNT injections in various rheumatic conditions that were recently reviewed by Khenioui and colleagues  [62]. Although the 16 reviewed studies were heterogeneous and had various shortcomings that prohibited the reaching of a generalized conclusion with a satisfactory level of confidence, the reviewing authors did notice that they provided some trend towards the anti-nociceptive effect of intra-articular BoNT/A. Such results show that more research is necessary to understand the mechanism of action and the behaviour of the botulinum toxin when being injected intra-articular.
However, no statistically significant differences were found between the two groups in this study when using other assessment methods. Similarly, a systematic review of the literature for the use of BoNTs for the prevention of hypertrophic scars that included ten clinical studies, found improved cosmetic outcomes among certain studies. However, due to the heterogeneity of the studies, as well as other factors, the authors concluded that the data were not supportive of the clinical usage of BoNT for this indication at this time, but recommended randomized controlled trials to reach a firm conclusion  [95]. At the time of writing, April 2018, two randomized controlled clinical trials are currently ongoing (NCT02623829 and NCT02886988). While the clinical data are thus suggestive, but presently are not yet conclusive, preclinical experimental work has provided evidence that BoNTs do have beneficial effects in wound healing.
, was the use of liposomes of a controlled size range to deliver BoNT/A for hyperhidrosis. Anterios was acquired by Allergan plc in 2016. In 2015, the lead Anterios formulation, ANT-1207, entered a phase 2 trial (NCT02479139) for axillary hyperhidrosis. Allergan have yet to report on the outcome of this study. Chajchir and colleagues reported on the use of a microcrystal and nanoparticle formulation, InParT (Transdermal Corp), reconstituted with Botox ® at 2 U/mL for transdermal delivery in the treatment of upper facial lines  [158]. The formulation was found to be effective versus placebo based on patient reported Facial Line Outcome scores. The formulation was applied daily for a period of 4 to 7 weeks, with a 12 week follow up period. The improved outcome scores were maintained during the whole study period.
2007). To propose an atlas of left hemisphere high-order language areas, we first combined multiple-language fMRI task-induced activation mapping and conjunction analysis to select a set of both activated and leftward asymmetrical areas during sentence processing. Second, we clustered the regions identified in the first step into networks based on their intrinsic connectivities at rest. Third, we applied graph analysis to characterize the roles of the regions in communication within and across networks. To this end, we utilized BIL&GIN, a database dedicated to the study of hemispheric specialization  (Mazoyer et al. 2015) , and selected 144 righthanders who were mapped during sentence production, reading and listening tasks compared to the production, reading and listening of lists of words, respectively.
Participants From the BIL&GIN database, we selected 144 healthy right-handers (72 women) who completed the fMRI battery, including several language tasks  (Mazoyer et al. 2015). The sample mean age was 27 years (SD = 6 years), and the women were two years younger than the men (women 26 ± 5; men: 28 ± 7, p = 0. 053). The mean educational level of the participants was 16 years (SD = 6 years), with no significant difference between the men and women (p > 0. 05). All participants reported themselves as right-handed; their mean normalized finger tapping test asymmetry ([(right number of taps -left number of taps)/(left + right number of taps)] × 100) was 6. 25 (SD = 4. 3), and their mean Edinburgh score was 93. 5 (SD = 11), confirming their right-handedness. There was no difference between gender for the Edinburgh score (p = 0.
Image analysis Functional imaging analysis common to task-induced and resting-state acquisitions For each participant, (1) the T2*-FFE volume was rigidly registered to the T1-MRI; (2) the T1-MRI was segmented into three brain tissue classes: grey matter, white matter and cerebrospinal fluid; and (3) the T1-MRI scans were normalized to the BIL&GIN template including 301 volunteers from the BIL&GIN database (aligned to the MNI space) using the SPM12 "normalise" procedure with otherwise default parameters. For each of the three fMRI runs, data were corrected for slice timing differences. To correct for subject motion during the runs, all the T2*-weighted volumes were realigned using a six-parameter rigid-body registration. The EPI-BOLD scans were then registered rigidly to the structural T2*-FFE image.
BOLD signal variations were measured in 192 pairs of functionally defined hROIs of the AICHA atlas  (Joliot et al. 2015)  adapted to SPM12, excluding 7 hROIs pairs belonging to the orbital and inferior temporal parts of the brain in which signals were reduced due to susceptibility artefacts. For each participant, we computed contrast maps of the three language conditions. We then calculated the right and left hROI BOLD signal variations for each of the 185 remaining pairs by averaging the contrast BOLD values of all voxels located within the hROI volume. Specific analysis of resting-state functional images Time series white matter and cerebrospinal fluid (individual average time series of voxels that belonged to each tissue class) and temporal linear trends were removed from the rs-fMRI data series using regression analysis.