dataesr/scientific-paragraphs-categorization huggingface dataset:
Our study has several limits First, the number of patients especially in the inappropriate IAT group was low. We can explain the small number of patients by the very selected population we studied. But to our knowledge, this is the second largest cohort of IAI growing with Enterococcus after Kaffarnik et al. 's cohort  [21]. However, because the population is highly selected, the results of our study should only be taken as an exploratory approach and further studies are needed to confirm those results. Second, this is a retrospective study although data was extracted from a multicentric national database in which data are collected prospectively. Presence of missing data led us to read medical records, but since almost one third of medical records were not available, we had to exclude nearly a hundred of patients.
We identified similar proportions of all NPCs, cortical NPCs, and hindbrain NPCs in all species. This analysis further indicated that there was no detectable speciesdependent bias in regional patterning. To gain insights into differences in gene expression between human, chimpanzee and bonobo NPCs, we performed high-throughput RNA sequencing (RNA-seq) analyses on eight human and five nonhuman primate (chimpanzee and bonobo) NPC lines. We assessed the RNA-sequencing data from NPCs for developing brain regional signatures. Using BrainImageR tool  (Linker et al. , 2019) , we calculated the enrichment of each differentially expressed gene (described on Supplementary file 1) within tissues of the developing brain. Genes upregulated in Homo NPCs exhibited similar regional enrichment to genes upregulated in Pan (chimpanzee and bonobo) NPCs, indicating that the differences observed in RNA sequencing were not influencing broad fate specification between NPCs from Homo versus Pan (Figure  1 -figure supplement 1D).
01, Mann-Whitney U test), showing that chimpanzee and bonobo NPCs migrate longer distances at higher speeds compared to human NPCs. (G-H) Migration analysis using neurosphere outgrowth assay. (G) Representative images of iPSC forebrain neurospheres from human and chimpanzee showing differential outgrowth migration of NPCs. The average distance between the radius of the inner neurosphere and outer circumference of cells was calculated using (DAPI)-stained nuclei (blue). Four measurements were taken and averaged for each neurosphere (examples of distances shown in red). (H) Graph showing quantification of distances migrated by human, chimpanzee and bonobo NPCs. The data confirmed that NPCs from chimpanzees and bonobos migrate longer distances than human NPCs. Comparative statistics as follows: Human versus Chimpanzee, p=0.
Neurosphere migration assay The neurosphere migration assay described here was performed according to previously published protocols  (Brennand et al. , 2015; Delaloy et al. , 2010). Briefly, NPCs were dissociated with Accutase and then cultured for 72 hr in non-adherent plates to generate neurospheres. Neurosphere culture is defined as a culture system composed of free-floating clusters of NPCs. Neurospheres were then manually picked and plated in Matrigel matrix (0. 5 mg Matrigel was used to coat a 24-well plate 1 hr before neurosphere plating) and fixed 48 hr later to access NPC migration. Average NPC migration distance from each neurosphere was measured using Image J software (NIH).
Multielectrode array analysis (MEA) Using the 96-well MEA plate from Axion Biosystems, we plated cells derived from four humans, two chimpanzees and two bonobos (two clones from each line) and we repeated the experiment three times. Each well was seeded with 15,000 NPCs that were induced into neuronal differentiation as described previously and summarized on Figure  5A. Each well was coated with poly-ornithine and laminin prior to cell seeding. Cells were fed three times a week and measurements were taken before media changes. Recordings were performed in a Maestro MEA system and AxIS software (Axion Biosystems) using a bandwidth with a filter for 10 Hz to 2. 5 kHz cutoff frequencies. Spike detection was performed using an adaptive threshold set to 5. 5 times the standard deviation of the estimated noise on each electrode.
Each plate rested for 10 min for acclimatization in the Maestro instrument and then was recorded for an additional 10 min to calculate spike and burst rates. Multielectrode data analysis was performed using the Axion Biosystems Neural Metrics Tool, and an active electrode was considered once five spikes occurred over the period of 1 min (five spikes/min). Bursts were identified in the data recorded from each individual electrode using an adaptive Poisson surprise algorithm. Network bursts were identified for each well, using a non-adaptive algorithm requiring a minimum of 10 spikes with a maximum inter-spike interval of 100 ms.
Acknowledgments This work was supported by the  National Institutes of Health (NIH)  grants  MH095741 ,  MH088485 ,  DP2-OD006495-01 ,  R01MH094753 ,  R01MH103134 ,  R01MH100175 ,  K99MH101634 , and  U19MH107367 ; the  California Institute for Regenerative Medicine (CIRM)   TR2-01814  and  TR4-06747 ; a  NARSAD Independent Investigator award ,  The G Harold and Leila Y Mathers Foundation ,  The Leona M. and Harry B Helmsley Charitable Trust , and  JPB Foundation. KP is supported by  NIH   MH101634 ,  MH113924 , a  Crick-Jacobs Junior Fellowship , a  NARSAD Young Investigator Award ,.
Neuro-Oncology Advances Scientific, USA) coupled to a nanospray Q-Exactive hybrid quadruplole-Orbitrap mass spectrometer (Thermo Scientific, USA). Each peptide extract were loaded onto a 300 µm ID × 5 mm PepMap C 18 precolumn (Thermo Scientific, USA) at a flow rate of 20 µl/min. After 3 min desalting, peptides were online separated on a 75 µm ID × 25 cm C 18 Acclaim PepMap RSLC column (Thermo Scientific, USA) with a 4-40% linear gradient of solvent B (0. 1% formic acid in 80% ACN, solvent A: 0. 1% formic acid in H 2 O) in 108 min. The separation flow rate was set at 300 nl/min. The mass spectrometer was operated in positive ion mode at a 1. 8 kV needle voltage. Data were acquired using Xcalibur 3. 1 software in a data-dependent mode. Full MS scans in the range from m/z 300 to 1600 were recorded at a resolution of 70,000 at m/z 200 and the target value for the automatic gain control (AGC) algorithm was set to 3 × 10 6 ions collected within 100 ms.
MS Data Processing and Quantification Mascot 2. 5 algorithm through Proteome Discoverer 1. 4 Software (Thermo Fisher Scientific Inc. ) was used for protein identification in batch mode by searching against a Mus musculus database (Proteome ID UP000000589; release date November 15, 2018; 54,188 proteins) merged to a Homo sapiens database (Proteome ID UP000005640; release date November 17, 201pretty8; 73,931 proteins) from http://www. uniprot. org/ website. 8 Two missed enzyme cleavages were allowed. Mass tolerances in MS and MS/ MS were set to 10 ppm and 0. 02 Da. Oxidation of methionine, acetylation of lysine, and deamidation of asparagine and glutamine were searched as dynamic modifications. Carbamidomethylation on cysteine was searched for as a static modification. For protein quantification, raw LC-MS/ MS data were imported in Proline Studio (http://proline.
Experimental Reproducibility Between Triplicates Protein quantifications were analyzed using a bespoke pipeline of python scripts. For human data set, there were 743 proteins in each brain sample and 517 proteins for the mouse data set. We estimated the dispersion of protein quantification values between technical replicates (3 per sample) for each condition (angiogenic and invasive) by computing the coefficient of variation CV= σμ, where σ and μ are the standard deviation and mean. Histograms of CV values were built for each sample separately for each condition. Based on the analysis of these histograms, we chose CV=0. 8 as the threshold for eliminating proteins whose values were not sufficiently reproducible between triplicates. Proteins were retained only if the CV was below the 0. 8 threshold for both conditions, resulting in 574, 691, and 714 proteins for each of the brain samples for Human and in 372, 468, and 484 proteins for each of the brain samples for mouse.
Functional Enrichment Analysis For the enrichment analysis, the significantly differentially expressed proteins (padj<0. 01) in the aggregated data sets were further filtered by the logFC criterion. We have retained proteins having the |logFC|>1 for both Human-and mouse-aggregated data sets. In order to find pathways deregulated between the two conditions of interest, we subsequently performed a Gene Set Enrichment Analysis (GSEA) on these subsets. We used Gseapy python package (https://pypi. python. org/pypi/gseapy), which is a wrapper to the functionalities provided by the Broad's institute GSEA suite (http://www. broad. mit. edu/gsea/). We used the enrichment function, applying a 0. 05 adjusted P-value cutoff, and ran the analysis using the GO biological process and GO cellular component knowledgebases.
Histological and Immunohistological Analyses For immunofluorescence on histological sections, frozen sections were processed as described previously. 6 Patient paraffin-embedded sections were deparaffinised in xylene and hydrated serially in 100%, 95%, and 80% ethanol. Endogenous peroxidase was quenched in 3% H2O2 in PBS for 10 min. Slides were then incubated with anti-DNM1 (Invitrogen PA1660), anti-PLP1 (Sigma SAB2101830), or anti-Nestin (ThermoFisher PA5-11887) antibodies overnight at 4°C. Sections were washed three times in PBS, and secondary fluorescent antibodies were applied (Anti-mouse or anti-rabbit fluorescent antibodies). After mounting, DNM1 or PLP1 expression localizations were analyzed using IHC profiler from Fiji Software. IHC profiler uses the DAB signal in images and the results are expressed as a ratio the DAB area to the total area.
Invasion Assays in Collagen I Gels P3 spheroids were prepared 3 days, respectively, before inclusion by the seeding of 10 4 cells in neurobasal medium with 0. 4% methylcellulose (Sigma) in a U-bottom 96 wells plate (Falcon). A solution of 1 mg/ml of collagen I (Fisher Scientific) was prepared in PBS with 7. 2mM NaOH. Treatments were mixed directly into the collagen gels. After 30 min incubation on ice, spheroids were individually picked, washed in PBS, and included in the collagen solution. After 45 min at 37°C in a cell incubator, neurobasal medium with the different treatments was added. P3 spheroid invasion areas were measured after 24 h with FiJi software, with a home-made macro. Briefly, total area was automatically quantified and the core area was manually measured. The core area was then subtracted from the total area for obtaining the invasive area.
Neuro-Oncology Advances which unidentified protein candidates were discovered for tumor classification  16  or for invadopodia structure. 17 When stringent statistical conditions were applied (padj<0. 01 and logFC>2), 34 Human proteins were overexpressed and 118 were downregulated in invasive areas (out of 152 proteins present in the aggregated dataset). Our analysis also included the estimation of an AngioScore. This latter approach was already successfully used in a previous publication from our team. 11 In the AngioScore, we compared the 30 best hits between core and invasive areas, and confirmed enrichment angiogenesisrelated proteins in the core area. Furthermore, the AngioScore was significantly reduced in the invasive area. To reinforce the validity of our analysis, we only selected proteins which were overexpressed in the different tumor areas of three different animals.
20 In glioblastoma, DNM1 was recently characterized as a marker of long-term patient survival in a computational analysis. 21 At a biological level, DNM1 was found to form a complex with Cortactin in glioma cells. 14 ur data are not in agreement with a publication which reported a role of DNM2 in glioblastoma invasion using the standard glioblastoma cell lines LN444 and SNB19. 22 NM2 is highly expressed in all cancer types contrary to the expression of DNM1, which is mainly expressed in glioma, as referenced in TCGA. Furthermore, DNM2 is not a good prognosis marker for glioblastoma patient survival (TCGA database). Dynamin 2 was also recently described as a potential therapeutic target for glioblastoma development. 23 In our analysis, 2′,3′-cyclic-nucleotide 3′-phosphodiesterase (CNP, log2 fold change of 1.
Neuro-Oncology Advances We validated the regional expression of PLP1 and DNM1 by analyzing their RNA expression in the Ivy Glioblastoma Atlas Project database. Both candidates were found upregulated in the infiltrative tumor (IT), and the leading edge (LE) when compared with core areas (Cellular Tumor-CT). These areas were defined by histological characteristics, by evaluating the number of tumor cells in the sections. This correlation indicates that both tumor genes and proteins are involved in glioblastoma invasion. Our study differs from the previous proteomics analysis where two different PDX glioblastoma models (angiogenic or invasive) were compared. 25 In the latter analysis, Annexin A2 (ANXA2) and Calnexin (CNX) were found upregulated in the angiogenic model. A second proteomics study, from the same group, investigated effects of bevacizumab, which significantly modulated the tumor proteome.
Acknowledgments This work was supported by grants from  Institut National de la Santé et de la Recherche Médicale (INSERM)  (recurrent funding), and from the  "Ligue contre le Cancer" and the "Conseil Régional Nouvelle Aquitaine"  to A. B. , by  Helse Vest ,  Haukeland Hospital , The  Norwegian Research Council and Stiftelsen Kristian Gerhard Jebsen Research Foundation  for R. B. and by the  "Plan Cancer " for J. R. The Oncoprot platform was supported by  Nouvelle-Aquitaine Region  with  European Regional Development Fund.
W hether mechanical thrombectomy is beneficial in is- chemic stroke patients presenting with low ASPECTS (Alberta Stroke Program Early CT Score) remains uncertain, because only a few of these patients were enrolled in the recent pivotal thrombectomy trials. 1,2 Correspondingly, the current American Stroke Association /American Heart Association Background and Purpose-If anterior circulation large vessel occlusion acute ischemic stroke patients presenting with ASPECTS 0-5 (Alberta Stroke Program Early CT Score) should be treated with mechanical thrombectomy remains unclear. Purpose of this study was to report on the outcome of patients with ASPECTS 0-5 treated with mechanical thrombectomy and to provide data regarding the effect of successful reperfusion on clinical outcomes and safety measures in these patients.
Methods-Multicenter, pooled analysis of 7 institutional prospective registries: Bernese-European Registry for Ischemic Stroke Patients Treated Outside Current Guidelines With Neurothrombectomy Devices Using the SOLITAIRE FR With the Intention for Thrombectomy (Clinical Trial Registration-URL: https://www. clinicaltrials. gov. Unique identifier: NCT03496064). Primary outcome was defined as modified Rankin Scale 0-3 at day 90 (favorable outcome). Secondary outcomes included rates of day 90 modified Rankin Scale 0-2 (functional independence), day 90 mortality and occurrence of symptomatic intracerebral hemorrhage. Multivariable logistic regression analyses were performed to assess the association of successful reperfusion with clinical outcomes. Outputs are displayed as adjusted Odds Ratios (aOR) and 95% CI.
BEYOND-SWIFT Registry BEYOND-SWIFT was a retrospective, international, multicenter observational registry. The participating centers contributed records of consecutive acute ischemic stroke patients, who were treated with a CE-labeled market-release neurothrombectomy device manufactured by Medtronic (Dublin, Ireland). Further information on the registry and participating centers can be found in Information I and Table  I  in the online-only Data Supplement. The centers provided 2047 patient datasets, of whom 1 missed baseline characteristics such as age, sex, and admission National Institutes of Health Stroke Scale (NIHSS). Consequently, a total of 2046 patients were included into the registry. Most patients included in the BEYOND-SWIFT registry were treated for large-vessel occlusion (intracranial ICA, M1, and M2) anterior circulation strokes (n=1820).
Of these, 1630 had documented 90-day follow-up including 1532 with records of preinterventional ASPECTS. Two-hundredthirty-seven patients presented with ASPECTS 0-5 (Figure  1  for study flowchart). Data gathered within the framework of this registry will be made available for replication or further collaboration on request to Prof. Dr Urs Fischer and after clearance by the local ethics committee in Bern.
11 ASPECTS was evaluated at each site (Table I in the online-only Data Supplement) and was based on admission CT in 910/1532 cases of anterior large-vessel occlusion. In 600 cases, ASPECTS was rated on diffusion-weighted magnetic resonance imaging, and in 22 cases, no information on the admission imaging modality was provided. Functional clinical outcome was evaluated using the modified Rankin Scale (mRS) at 90 days, which was evaluated by a physician or a trained and certified mRS nurse usually not involved into acute treatment of the patient (Table  I  in the online-only Data Supplement). All participating centers evaluated the mRS on routinely scheduled and standardized telephone interviews or clinical visits. Neurological symptoms on admission and 24 hour after the intervention were evaluated by a stroke neurologist applying the NIHSS.
Statistical Analysis For the present analysis, a protocol with predefined outcome variables was written before analysis or inspection of the data began (https:// clinicaltrials. gov/ProvidedDocs/64/NCT03496064/SAP_000. pdf). The primary end point of this analysis was mRS score 0-3 (favorable outcome) at day 90. 12 Secondary and safety outcomes consisted of mRS score 0-2 (functional independence) at day 90, major early neurological improvement (defined as admission NIHSS-24h NIHSS ≥8 or 24h NIHSS <1),  13  all-cause mortality at day 90, and sICH. Univariate comparisons were made using standard statistical measures (Fisher exact test for categorical variables, Mann-Whitney U test for nonnormally continuous, or ordinally scaled variables and Welsch t test for normally distributed data). Association of successful reperfusion with all outcome parameters was assessed using multivariable logistic regression adjusting for the following prespecified confounders: age, sex, NIHSS on admission, tandem versus nontandem (tandem defined as >90% cervical stenosis or cervical occlusion), center (categorical, contrast type: indicator, comparator: largest center), ASPECTS ≤3 versus ASPECTS 4-5, intravenous thrombolysis, risk factor hypertension, dyslipidemia, smoking, previous stroke, diabetes mellitus, in-hospital stroke, type of admission imaging, intracranial ICA/carotid-T versus M1/M2.
For sensitivity purposes, analyses were rerun either with confinement to a cohort presenting with ASPECTS 0-4 or with implementation of the following interaction terms: 1. Successful reperfusion (1: successful) * admission modality (1: CT). 2. Successful reperfusion (1: successful) * age ≤70 years versus >70 years (1: age≤70). In a final sensitivity analysis, diffusion-weighted imaging (DWI) ASPECTS were increased by 1 point to estimate corresponding CT-ASPECTS as suggested by findings derived from the SAMURAI registry. 6 Thereafter, the population of ASPECTS 0-5 was recalculated and analyses were rerun. This analysis was added to the statistical analysis plan after protocol finalization and data inspection.
Results of the logistic regression output by strata of admission imaging modality are shown in Figure VI in the online-only Data Supplement. A significant effect of reperfusion was still observed for mRS score 0-3 and mortality in both subgroups, however, uncertainty increased considerably (especially for CT). In a subcohort of patients with successful reperfusion, achieving TICI 3 instead of only TICI 2b was found to result in additional benefit (Figure IV in the online-only Data Supplement). When analyses were confined to patients with ASPECTS 0-4 (N=144), the positive association between successful reperfusion and the outcome variables remained statistically significant only for mortality (aOR, 0. 168; 95% CI, 0. 056-0. 499; Table  3  and Figure VII in the online-only Data Supplement). In a final sensitivity analyses, DWI-ASPECTS was increased by 1 point to estimate corresponding NCCT-ASPECTS and transferability to CT imaging in line with the findings observed in the SAMURAI registry (Stroke Acute Management With Urgent Risk-Factor Assessment and Improvement).
Non-breeding Destination Combined geolocation-immersion loggers (Mk 19, 15, and 5, British Antarctic Survey, Cambridge UK) were deployed on 77 of these individuals across the four colonies. Loggers were attached with two cable ties to a plastic ring, which was then fitted to the tarsus and remained in place for up to 2 years before the bird was recaptured at the breeding colony. The total mass of the attachment did not exceed 10 g, representing <0. 35% of average adult body mass, and so unlikely to have any adverse effects  (Bodey et al. , 2018a). The loggers sampled ambient light every minute and recorded the maximum value every 2, 5, or 10 min (Mk 19, 15, and 5 loggers, respectively). Positions were calculated from logger data following established methods  (Wilson et al. , 1992; Phillips et al.
, 2004). Briefly, the timings of sunset and sunrise were estimated using TransEdit2 (British Antarctic Survey, Cambridge UK) using a light-intensity threshold of 16. A minimum dark period of 4 h was set to remove any light-dark transitions created by shading or cloud cover. Latitude was derived from day length, and longitude from the timing of local midday and midnight, with respect to Greenwich Mean Time and Julian day, providing two positions per day with an accuracy of ∼200 km  (Phillips et al. , 2004). Examination of individual migration tracks revealed latitude to be the major axis of movement, with birds tending to migrate southward from the breeding colonies toward northwest Africa  (Fort et al. , 2012 ; Figure  2 ). Plots of displacement from the colony indicated that all individuals reached their final non-breeding destinations by December and remained in this region for a minimum of 1 month before commencing their return migration.
Consistency in Non-breeding Strategies and Isotopic Clustering To examine the consistency of non-breeding destination and stable isotope ratios we calculated the repeatability of these traits based on the intra-class correlation coefficient from linear mixed-effect models fitted with bird ID as a random intercept, using the package "rptR" v. 0. 9. 21  (Stoffel et al. , 2017). We used repeatability as a proxy for behavioral consistency, testing the hypothesis that between-individual variance in a particular trait was greater than within-individual variance  (Patrick et al. , 2014). To estimate the consistency of non-breeding destinations we calculated the repeatability of mean December latitude and longitude for those individuals from Bass Rock (n = 22) and Rouzic (n = 21), that were tracked over two consecutive years.
To estimate the consistency in stable isotope ratios during the non-breeding season we calculated the repeatability of δ 13 C and δ 15 N in primary feathers of individuals from Bass Rock (n = 27) and Grassholm (n = 13) sampled in two consecutive years. The three individuals from Great Saltee were excluded from the estimate of isotopic repeatability due to the small, multi-year sample size (Table  1 ). To test for the occurrence of distinct dietary clusters in stable isotope ratios we fitted a multivariate normal mixture model to δ 13 C and δ 15 N values using the package "mixtools" v. 1. 1. 0 (Benaglia et al. , 2009). The best-fitting model was selected by comparing the log-likelihood of candidate models with differing numbers of clusters. Feather samples were assigned to a dietary cluster based on a probability of assignment >0.