dataesr/scientific-paragraphs-categorization huggingface dataset:
The software computes logFoldChange and p-values of genes in a given comparison, ranks them, and scores the genes according to their rank. It gives an enrichment score (ES) depending on the over-representation of genes of a given predefined gene set in one of the conditions. This score is normalized (NES) and a statistical value is given (p-value). The RNA-seq data were deposited under the GEO reference GSE178260. Transcription factor enrichment analysis was performed using Enrichr  [41]. For analysis of the activated/inhibited pathways, we used Ingenuity Pathway Analysis (IPA, Ingenuity Systems, Inc. , Redwood City, CA, USA). Molecules from the data set that were associated with Ingenuity Knowledge Base were considered for the analysis. We included only the significantly differentially expressed genes with no cutoff for the fold change.
Elaboration of Publicly Available Data from GBM Patients The integrin a6 gene expression pattern across glioma patients was investigated using publicly available cohorts. The Cancer Genome Atlas (TCGA)  [42]  and REMBRANDT datasets  [43]  were downloaded from the GlioVis portal (http://gliovis. bioinfo. cnio. es/, accessed on 20 March 2020)  [44]. Samples were classified according to molecular subtype following available GlioVis tool as described in  [25]. Gene expression data of the GSCs collection were retrieved from Gene Expression Omnibus (GEO). The two independent interrogated datasets were GEO accession GSE49009 (Bhat cohort; 11 PN-GSCs and 6 MES-GSCs)  [26]  and GSE67089 (Mao cohort; 6 PN-GSCs and 4 MES-GSCs)  [27]. For the ITGA6 expression in the two-dimensional representation according to the new integrative GBM classification model  [45] , refer to the Broad Institute Single Cell Portal website (https: //singlecell.
Statistical Analysis Data graphs are presented as means ± SEM (standard error of the mean). Statistical analyses were performed using the GraphPad Prism ® software. Statistical tests used for each experimental data collection are specified in each figure caption. Calculated p-value is summarized in figure panels as * p < 0. 05; ** p < 0. 01; *** p < 0. 001; **** p < 0. 0001. Different tests were used to assess statistical significance according to data distributions and to the nature of comparison (unpaired t-test with or without Welch's correction, Mann-Whitney test, and two-way ANOVA). Every test used is specified for each panel in the figure caption.
Integrin a6 Is Expressed in Proneural and Mesenchymal GBM Subtypes To better understand the significance of integrin a6 in GBM, we analysed in silico the ITGA6 expression in the two most important GBM subtypes. Data extracted from two distinct datasets of GBM patients  [42, 43]  showed that ITGA6 expression was greater in GBMs compared with non-cancerous samples (Figure  S1A ) and that MES subtype expresses significantly higher levels of ITGA6 than PN GBMs (Figure  S1B ). In addition, in line with this, ITGA6 expression was greater in the MES-GSCs in a dataset obtained from in vitro patient-derived GSCs  [27]  (Figure  S1C ). Even taking into consideration the recent integrative model that tuned the previous classification into four molecular subtypes  [45] , ITGA6-expressing cells were specifically enriched in the MES-like state (Figure  S1D ).
MES-GSC82 and MES-GSC90 were therefore differentiated in serum-containing media and integrin a6 protein level was analysed at 7 days. ITGA6 expression strongly decreased upon differentiation stimuli together with NES expression (Figure  1D ) and was totally undetectable in differentiated glioblastoma cells (DGCs) derived from the same postsurgical specimen (Figure  S2C )  [32]. To sum up, our findings demonstrate that ITGA6 is expressed in both PN and MES GBM subtypes and derived GSCs and is associated with a dedifferentiated status. Given the demonstrated association between integrin a6 and stemness in CD133 HI PN settings [22], we wondered whether the differentiation state would also inhibit ITGA6 expression in the MES subtype. Nestin (NES) level was quantified along with ITGA6 expression as a GBM stemness marker  [5] , which characterizes GSCs irrespective of their molecular subtype, as demonstrated by previously published data (Figure  S2D )  [26].
Integrin a6 Supports Stemness in PN-GSCs, but Not in MES-GSCs As previously shown, ITGA6 knockdown in Olig2 HI PN-GSCs results in abrogation of stem-related features, such as self-renewal reduction and proliferation arrest  [22]. To explore whether integrin a6 regulates the same cellular functions in MES-GSCs, we compared FACS-sorted ITGA6 HI and ITGA6 LO subpopulations (Figure  1E ) enriched following the gating strategy specified in Figure  S2E. Cells were seeded at single-cell clonal density and the capacity to form gliomasphere, and their diameter were evaluated. Gliomasphere-forming capacity and variation in sphere size roughly reflect stem cell frequency/stem cell potential and proliferation rate, respectively  [49] [50] [51] [52] [53]. Consistently with published data on PN-GSCs [22], PN-GIC2-ITGA6 LO showed a significant reduction in clonogenic capability and sphere size (Figure  1F ).
Analysis of TCGA datasets in glioma patients confirmed significant positive correlation of ITGA6 expression with CDK1, CDK4, PCNA, and FOXM1 transcript levels (Figure  S5A, B ). Based on these data, high levels of integrin a6 potentially convey resistance to DNA damaging therapies in MES-GSCs. To gain further insights into the biological value of the ITGA6 expression in the mesenchymal setting, we performed Ingenuity Pathway Analysis (IPA). Interestingly, IPA predicted that ITGA6 induces the TP53 pathway inhibition, thus activates FOXM1 and inhibits CDKN1A (p21) and E2F4 (Figure  3F ). As a consequence, the molecular alterations happening in ITGA6-silenced cells convey increased cell morbidity, senescence, and necrosis (Figure  S4H ). Recently, the inhibition of integrin a6 has been described as negatively impacting on the FOXM1 regulatory node in an ERK-dependent manner in Oligo2 HI GSCs (PN-GSCs)  [54].
: Kaplan-Meier survival curves in glioma TCGA publicly available database. Full website blot Figures can view at the supplementary file. Author Contributions: Experimental design conceptualization, E. S. , F. M. -S. , and A. T. ; investigation, methodology, and formal analysis E. S. , F. M. -S. , G. S. , and A. N. -C. ; shRNA lentiviral vectors methodology, L. P. (Leire Pedrosa) and N. d. l. I. ; shRNA lentiviral vectors formal analysis, E. S. , L. P. (Leire Pedrosa), and F. M. -S. ; proneural/mesenchymal characterization of the GSCs line, N. d. l. I. , E. S. ; samples handling for the RNA-seq, O. A. ; bioinformatical analysis and RNA-seq data curation, G. S. , G. B. , and A. E. -C. ; writing-original draft preparation, E. S. , G. S. , F. M. -S. , and A. T. ; writing-review and editing, E.
Acknowledgments: We thank the  Tumor Microenvironment Laboratory at Institut Curie  for critical reading and insightful suggestions;  Joan Gil  for scientific support and critical reading of the manuscript; technicians of the  Applied Radiobiology and Experimental Radiotherapy Group (ICO)  for the use of irradiation facilities;  Ester Castaño ,  Beatriz Barroso  and  Benjamín Torrejon  of the  Scientific and Technological Center of the Health Sciences Campus of Bellvitge  for excellent technical assistance. The IPA was conducted with the support of the Paris Brain Institute Data and Analysis core (iconics. institutducerveau-icm. org/) through funding provided by the institute. We acknowledge  Marta Alonso  ( Department of Oncology, University Hospital of Navarra, Pamplona, Spain ) and  Candelaria Gómez-Manzano  ( Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA ) for sharing some of the GSCs cell lines used in the present study.
Funding: This work was supported by  Agència Gestió Ajuts Universitaris i Recerca, Generalitat de Catalunya , grant number  2017SGR1014 );  Red Temática  de investigación cooperativa en cáncer, grant number  RD12/0036/0029 );  School of Nursing , grant number  PREI-UB 17/005I ;  18/010I ;  19/009A ; the  Fondation ARC pour la recherche sur le cancer , the  INSERM-CNRS ATIP-Avenir grant , the  European Research Council (ERC)  under the  European Union's Horizon 2020  (grant agreement no. 805225 ) and the  NanoTheRad (Paris-Saclay University ). High-throughput sequencing was performed by the  ICGex platform of the Institut Curie  supported by the grants  ANR-10-EQPX-03 ,  ANR-10-INBS-09-08 , and  INCa-DGOS-4654. Work of M. M. and L. P. is supported by  Fondazione AIRC per la Ricerca sul Cancro  ( IG 18851 ).
Consequently, it is difficult to give an accurate value for the real number of grains contributing to the diffracted intensity and only a range is possible to give between 100 and 5000 grains. Absorption has been recorded using a photo-diode placed in the direct beam. Setup was calibrated using a CeO 2 powder (NIST standard). Sample to detector distance and detector misalignment have been determined using pyFAI software  [19]. Calibrating powder and sample has been placed at the same position using a camera looking on sample top surface and performing absorption scans along x and y directions. Motor resolution for rocking curves was set to 0. 005°, meaning that the final alignment is better, due to the high number of points in the scan (30 above Full Width at Half Maximum typically); so the required resolution can be easily reached with the setup for 1 µm resolution along z direction.
In order to choose the best function, we need to test systematically this procedure by considering a big number of experimental data. All this procedure has been automatized in a Matlab handmade software with the implementation of validity criteria on the fitting quality. To simulate the background noise, a polynomial function is chosen whose order need to be tested. In the test, the peak and the background noise can be simulated together or separately. Several quality indicators are considered, such as: • Mean value indicator: it is an indicator on the average stress value, which is calculated from the stresses obtained from the different methods. The mean value indicator represents a comparison of the mean stresses of the different methods. • Variance indicator: it represents the difference between the re- sults and average stress value.
Data processing for stress determination When a material is deformed, the lattice spacing between the crystallographic planes d hkl expands or contracts, causing a shift in the position of the rings in the diffraction pattern. Changes in the lattice spacing between the crystallographic planes can be evaluated as a result by measuring this angular shift, which can then determine the elastic deformation. The strain on the direction e is: (3) = e e. (2) and ´is the elastic strain tensor, with the assumption that there is no shear strain (this assumption has been verified for the current experiments and has already been notified on similar previous experiments  [4, 12] ): = 0 0 0 0 0 0 xx yy zz (4) The strain along the direction e can be developed as: = + + cos sin sin sin cos xx yy zz 2 2 2 2 2 (5) The actual true/rational strain along the direction e can also be calculated by comparing the undeformed lattice spacing d 0 between the crystallographic planes with the deformed lattice spacing d.
Selected parts of the boule were ground and previously characterized by synchrotron x-ray powder diffraction  [12]. Rietveld analysis of the x-ray patterns using the FULLPROF package program  [22]  indicated that the crystal was a single phase without detectable impurities  [23]. The oxygen content of La 1. 5 Ca 0. 5 CoO 4. 02 was determined by cerimetric titration and an automatic Crison titrator. The studied single crystal displays an oxygen stoichiometry/nominal average Co oxidation state of La 1. 5 Ca 0. 5 CoO 4. 02 /Co 2. 54+  [12]. Magnetic measurements were carried out between 2 and 300 K by using a commercial superconducting quantum interference device (SQUID) magnetometer from Quantum Design. The measurements were performed warming the sample after zero-field cooling (ZFC) and field cooling (FC) conditions at two different external magnetic fields (0.
B. Neutron diffraction The structure analysis at room temperature was performed using single crystal neutron diffraction since this technique is more sensitive to the position of oxygen atoms than xray diffraction. The crystal symmetry at 295 K is confirmed as orthorhombic with a and b axes almost equal in length. The observed reflections agreed with an A-centered lattice arising from the distortion of the high temperature cell with a o ≈ √ 2a t. The crystal is heavily twinned in the ab plane. The A-centering cell implies some extinction rules (k + l = 2n + 1 and the comparison of the reflections allowed by each domain indicates that the crystal seems to have a perfect twinning with an even ratio of the two domains. Following previous studies  [26] , the experimental data were refined using the space group symmetry A2mm (no.
35, standard setting Cmm2). The results yielded by the best fit are summarized in Table  I. These results are similar to those published by Horigane et al. [26]  but we observe a minor polar distortion in our sample. In fact, our experimental data can be fitted using the centrosymmetric space group Ammm with similar accuracy. If we look at the errors derived for x coordinates (Table  I ), only one basal oxygen atom significantly shifts from the inversion center position. In the previous report  [26] , this happened with the apical oxygen atoms. We have applied a symmetry mode analysis using the AMPLIMODES program  [34]  to gain insights into the transition from the high temperature phase into the orthorhombic one. Table  II  shows the mode decomposition for this transition with a comparison of the normalized amplitudes between the two refinements.
ACKNOWLEDGMENTS These experiments were performed at BOREAS beamline at  ALBA  synchrotron with the collaboration of  ALBA  staff and we also acknowledge  Diamond Light Source  for beam time on instrument I10 under Proposal No. SI19996. We would also like to thank  ILL  for granting beam time (Experiment No. 5-41-1021 ). The authors would like to acknowledge the use of  Servicio General de Apoyo a la Investigación -SAI ,  Universidad de Zaragoza. For financial support, we thank the  Spanish Ministerio de Ciencia, Innovación y Universidades  (Project No. RTI2018-098537-B-C22  co-funded by  ERDF  from  EU)  and  Diputación General de Aragón  (Project No. E12-20R ).
5 • C). All measurements started at near air saturation (>98%). The O 2 concentration was measured every 60 s using the PyroOxygen Logger Software until O 2 was completely consumed in each well. Eight measurements were recorded simultaneously, with four replicas for each treatment. Once the measurements were taken, the number of larvae in each well was quantified using a Sedgewick-Rafter chamber for posterior standardization. Blank measurements were equally carried out using sterile seawater and sterile seawater with bacteria (in the absence of animals) to obtain the background and microbial respiration. RRs were calculated through linear regression by plotting air saturation as a function of time and corrected using the blank values. Only the values ≥70% of saturation were considered to avoid any possible (differential) influence of hypoxia on the animals.
5 µm 2. For each ROI, three values were calculated: (a) the average fluorescence of MTK-DR, (b) the average orange fluorescence for JC-10 aggregates, and (c) the average green fluorescence of JC-10 monomers. The ρm for each larva was calculated as the average value of all 10 ROIs. The m of a given ROI was calculated as the ratio between JC-10 aggregates and monomers, and the average of the 10 ROIs was considered as the value for a given sample. Then, the average ρm and m for each developmental stage and treatment was calculated. Fluorescence quantifications were made using the software FIJI-ImageJ2  (Schindelin et al. , 2012; Rueden et al. , 2017)  and the Bio-Formats plugin  (Linkert et al. , 2010).
ACKNOWLEDGMENTS The authors would like to thank  Laboratorio Central de Cultivos Marinos of the UCN  for providing the infrastructure for carrying out the experiments, especially  German Lira  and  Daniel Gonzalez  for animal maintenance. They also thank  Ana Mercado  and  Yohana Defranchi  for helping with the experiments, and  Rodrigo Rojas  for donating the VPAP18 strain. Finally, they thank the confocal facility (FONDEQUIP and  EQM140100 ) from the  Faculty of Medicine, UCN.
4B ). In the mesenteric lymph node, there was abundant fibrin, multifocal hemorrhages and small numbers of foamy macrophages within the subcapsular sinuses. There was marked congestion of the cortex, with edema and occasional necrotic cellular debris in lymphoid germinal centers (not shown). No significant findings were identified in other internal organs examined. The complete genome sequence of SARS-CoV-2 was obtained directly from the respiratory secretions (nasal, tracheal and oropharyngeal secretions) and feces from the affected cat. When compared to the Wuhan-Hu-1, the SARS-CoV-2 virus recovered from the cat in the present study presented 14 single nucleotide polymorphisms (SNPs). Lineage prediction using pangolin https://github. com/cov-lineages/pangolin/blob/master/github. com/covlineages/pangolin)  (17) (18) (19) (20) (21) (22)  identified the sequence as belonging to SARS-CoV-2 lineage B.
1. 240 which comprises a total of 2033 sequences in the GISAID dataset (accessed 2021-03-25). The sequence identified in the cat clustered with human SARS-CoV-2 sequences detected in Virginia or in nearby states. Phylogenetic analysis using Nextstrain (23) placed two SNPs, both encoding amino acid changes (A15659G, ORF1b: D731G; C29376T, N: P368L) on the terminal branch leading to the sequence from the cat. One SNP downstream of the parent node of the cat sequence was a group of 36 sequences from the Pacific Northwest (Oregon and Washington) while moving 1 SNP upstream to the next ancestor node added 17 sequences including 10 from Virginia (Fig. S1 ). Unfortunately, no SARS-CoV-2 sequences were recovered from rRT-PCR positive samples from the cat owners who tested positive for SARS-CoV-2. Therefore, it was not possible to establish a direct link between the virus recovered from the affected animal and the first person diagnosed prior to the animal or second the second person who tested positive for SARS-CoV-2 after the cat became clinical.
Study Design and Participants This randomized, multicenter placebo-controlled, singleblinded clinical study, 3V2640-CLIN-005, FASCINATE-1, enrolled subjects with clinical or histologic evidence of NASH (ClinicalTrials. gov, Number NCT03938246). This study was performed in accordance with ethical principles of the Declaration of Helsinki and consistent with the International Conference on Harmonization, Good Clinical Practice, and applicable regulatory requirements. The study population included male and female subjects aged 18 years and older with magnetic resonance imaging proton density fat fraction (MRI-PDFF) 8% and either biopsyproven NASH within 2 years before randomization or magnetic resonance elastography 2. 5 kPa during screening to sample a population of patients with NASH and fibrosis.
The organic phase was dried, reconstituted in acetonitrile/isopropanol (1:1), centrifuged, and transferred to vials for UHPLC-MS analysis as described previously. 19 An appropriate test mixture of standard compounds was analyzed before and after the entire set of randomized sample injections in order to examine the retention time stability, mass accuracy, and sensitivity of the system. Metabolomics data were preprocessed using the TargetLynx application manager for MassLynx 4. 1 (Waters Corp, Milford, MA). The [M þ NH 4 ] þ ion adduct of tripalmitin was followed, with a m/z ¼ 824. 771. Serum protein biomarkers were measured as follows: PRO-C3 by enzyme-linked immunosorbent assay at Nordic Bioscience (Herlev, Denmark), plasma N-terminal propeptide of type III procollagen (PIIINP) and tissue inhibitor of metalloproteinase 1 (TIMP1) by enzyme-linked immunosorbent assay at Siemens (Berkeley, CA), fibroblast growth factor-21 (FGF-21) by MesoScale Discovery at Precision for Medicine, cytokeratin-18 (CK18) proteolytic fragment CK18 (M30) and intact CK18 (M65) by monoclonal antibody enzyme-linked immunosorbent assay at Cerba.
3-to 1. 6-fold higher exposure compared to day 1, and relatively low variability between patients (Figure  1A ). The overall exposure of drug in the 25mg cohort (area under the curve 0-24 6580 ng/h * mL) was increased by 2. 6-fold in the 50-mg cohort (area under the curve 0-24 16,800 ng/h * mL), consistent with a linear dose proportionality, observed in prior studies with doses ranging from 25 mg to 200 mg in humans (data on file). FASN inhibition was assessed by measurement of serum tripalmitin, a triglyceride (TG) in which all 3 acyl chains are palmitate and its serum level provides an estimate of DNL. 24 ripalmitin increased by 26% in the placebo group and was reduced by 21% in the 25-mg cohort and by 40% in the 50mg cohort (P <. 01 and P <. 0001, respectively) after 12 weeks of treatment (Figure  1B ).
Decreased tripalmitin was evident by week 4 of dosing at 50 mg with a median decrease of 21% (P <. 05) from baseline, the earliest postbaseline timepoint tested (not tested for 25 mg). The reduction in this pharmacodynamic marker demonstrates significant inhibition of FASN and hepatic DNL by TVB-2640. Safety data were collected from a total of 99 patients, of whom 68 were treated with TVB-2640. Overall, 62 patients (63%) experienced at least 1 TEAE, all of which were assessed by the investigator as grade 1/mild except for 1 grade 2 urinary tract infection and 1 increased appetite at 25 mg, and 1 shortness of breath at 50 mg; all 3 resolved without dose adjustment. No on-treatment serious adverse events occurred in any dose group. Overall, the most common TEAEs, regardless of drug-relatedness, among TVB-2640-treated patients were headache (6 patients [9%]), peripheral edema, rash, and upper respiratory tract infection (4 patients [6%]), and bronchitis, diarrhea, nausea, and urinary tract infection (3 patients [4%]) and hypertriglyceridemia (noted as unrelated to treatment; 2 patients [5.
Methods and results A retrospective, longitudinal cohort of 421 patients diagnosed with HCM aged 1-16 years independent of the HCM Risk-Kids development and internal validation cohort was studied. Data on HCM Risk-Kids predictor variables (unexplained syncope, non-sustained ventricular tachycardia, maximal left ventricular wall thickness, left atrial diameter, and left ventricular outflow tract gradient) were collected from the time of baseline clinical evaluation. The performance of the HCM Risk-Kids model in predicting risk at 5 years was assessed. Twentythree patients (5. 4%) met the SCD end-point within 5 years, with an overall incidence rate of 2. 03 per 100 patient-years [95% confidence interval (CI) 1. 48-2. 78]. Model validation showed a Harrell's C-index of 0. 745 (95% CI 0. 52-0.
Methods Patients The study cohort comprised consecutively evaluated patients aged 1-16 years meeting diagnostic criteria for HCM from nine participating centres in the International Paediatric Hypertrophic Cardiomyopathy Consortium and the Sarcomeric Human Cardiomyopathy Registry (SHaRe) (Supplementary material online, Table  S1 ). SHaRe centres that had contributed data to the HCM Risk-Kids development cohort were excluded. Included patients were evaluated between 1995 and 2019. Hypertrophic cardiomyopathy was defined as a maximal left ventricular wall thickness (MLVWT) of more than two standard deviations (SDs) above the body surface area (BSA)-corrected mean in the absence of abnormal loading conditions that could account for the abnormality. 6 atients were excluded if they had a prior history of ventricular fibrillation or sustained ventricular tachycardia (VT), known inborn errors of metabolism or syndromic disease (e.