dataesr/scientific-paragraphs-categorization huggingface dataset:
We recorded the pressure signals with an analog-digital converter with internal hardware filters (low pass frequency set at 20 kHz, high pass frequency set at 0. 05 Hz, MP150, BIOPAC Systems Inc. ). We used the AcqKnowledge software to interpolate arterial pressure data at a frequency of 1000 Hz. We performed the measurements on an 84-year-old male patient with hypertension and no left ventricle dysfunction (i. e. left ventricle ejection fraction < 45%). We recorded the pressure data in two different configurations: the pre-clamp configuration as prior to aortic clamping (Fig. 1(a) ) and the post-clamp configuration during which the clamp was in place (Fig. 1(b) ). For each configuration, we chose a stable set of beats manually through a 20 to 40-second interval immediately before and after each clamp event.
To calculate P num , we solved Eq. (1) and imposed an arbitrary value of Q 0 such that the systolic volume V s , i. e. ventricular ejection volume over a heartbeat, was within the typical range of 70 to 90 mL. We defined the systolic (or stroke) volume as the integral of the input flow rate Q (t ) over one heart period T. We imposed the same stroke volume V s in both configurations. For each configuration we determined the optimal set of parameters P using the gradient-based method L-BFGS-B (from the initials of the original authors Broyden  [62] , Fletcher  [63] , Goldfarb  [64] , Shanno  [65] ) using the SciPy library from Python  [66]. The L-BFGS-B algorithm is a limited-memory Quasi-Newton method that solves large non-linear optimization problems. It allows bound constraints, in order to maintain each parameter within a physiological range  [67].
Methods participants. We use the cross-sectional data of 142 patients (72 FEP, 70 CHR-P) and 55 controls recruited in the FePsy (early detection of psychosis) study (see full Participants, Screening and Genotyping description in Supplementary materials). The PSRS data was obtained for a subsample of 61 patients: 32 FEP and 29 CHR-P, as well as for 14 controls. The data overlaps (n = 72) with our previous studies  57. All participants provided written informed consent and received compensation for participating. The studies had permission from the ethics committee beider Basel (EKBB). All methods were performed in accordance with the relevant guidelines and regulations. screening. The participants were assessed using the Basel Screening Instrument for Psychosis (BSIP)  92. Subjects selected for the study by screening subsequently underwent an entry examination, which included the Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Negative Symptoms (SANS), and a neuropsychological test battery.
A total of 87 SNPs that could be mapped to one of the top SNPs of the 108 loci associated with schizophrenia and that survived quality control were used to calculate the PSRS. The number of risk alleles per person was weighted for each SNP by the logarithm of its odds ratio as reported in the PGC SZ data set and summed across SNPs  97. The PSRS was then corrected for the first 20 genotypic principal components (PCs) and the number of SNPs used to calculate the PSRS by using the z-transformed residuals of a linear regression. Acquisition and analysis of MRI data. We obtained structural MRI scans within an average of 25 days after entry into our early detection service, using a 3 T MR imaging scanner (Siemens Magnetom Verio, Siemens Healthcare, Erlangen, Germany) with a 12-channel phased-array radio frequency head coil.
After the quality check of the main study population (Table  1 ), the full sample, with and without PSRS data, consisted of combined 22 CHR-P and 11 FEP subjects treated with antidepressants, 45 CHR-P and 57 FEP individuals without antidepressant treatment and 55 healthy controls. statistical analysis. The R software v. 3. 4. 0 with packages 'lmertest'v. 2. 0. 36, 'effects'v. 4. 0, 'emmeans'v. 0. 9. 1, 'car' v. 2. 1. 6 was used for statistical, group-related descriptive analysis. Adequate statistical tests (ANOVA, logistic regression, chi-squared test or t-test) were applied to examine group effects on the following variables of interest: age, sex, handedness, years of education, IQ, BPRS, PSRS, cannabis use, antipsychotics and antidepressants (Tables  1  and S1 ). Additionally the Pearson correlation coefficient was calculated for BPRS  98  , SANS and GAF score correlated with the anatomical data of each separate region.
The analysis of bias did not reveal a significant stratification of the analyzed population. We acknowledge several limitations. First, we used data extracted from available case reports through a systematic retrospective search. This strategy carries the risk of missing data. Second, laboratory findings were not available for all patients, which resulted in a decrease in the statistical power for univariate and multivariate analyses. Third, in the surgical setting, thromboembolic events potentially associated with N 2 O-induced hyperhomocysteinemia could have been mistakenly attributed to the postoperative context, leading to a potential underestimation of the thromboembolic risk associated with N 2 O exposure  [36, [41] [42] [43] [44] [45] [46] [47]. Fourth, in the present systematic review, the exclusion of non-English case reports could have potentially led to selection bias.
Moreover, by measuring the OCR and the proton production rate by cells in the extracellular medium, we can calculate the ATP production by OXPHOS and glycolysis in control and TFP-treated cells. Our results show that TFP-treatment induces significant changes in the amount of ATP produced by each source. In the control condition, the ATP produced by the OXPHOS metabolism was 92. 17 ± 1. 95 pmoles/min/1000 cells whereas in TFP-treated cells it dropped to 54. 23 ± 3. 38 pmoles/min/1000 cells. On the other hand, ATP produced by glycolysis in control cells was 15. 01 ± 0. 188 pmoles/min/1000 cells, whereas it was raised to 26. 51 ± 1. 86 pmoles/min/1000 cells in the treated cells, which represents 32. 83% of the total ATP produced upon treatment (Figure  2D ). Additionally, we validated our previous data by measuring lactate release in the extracellular medium.
LDH Assay, ATP Production, and Caspase-3/7 Activity Assay Cells were seeded at a density of 10,000 cells per well in 96-well plates. Cells were allowed to attach overnight and treated the next day for 24 h and further incubated for 24 h for the assay. After the incubation, ATP production, LDH release, and caspase-3/7 activity were measured using CellTiter-Glo (#G7571, Promega, Madrid, Spain), CytoTox-ONE (#G7890, Promega), and Caspase-Glo 3/7 assay (#G8091, Promega). The normalization of the data was done by the number of cells.
Annexin V/PI Staining After 24 h of incubations with the stimuli, cells were collected. Briefly, cells were washed with PBS and then detached with accutase (Gibco, Life Technologies) and resuspended in 100 µL of 1× annexin V-binding buffer. The reagent Pacific-Blue Annexin V (5 µL, BioLegend, San Diego, CA, USA) was added to the cell suspension for 15 min and incubated at room temperature. Then 400 µL of 1× annexin V-binding buffer was added to each sample. Propidium iodide (5 µL, Miltenyi Biotec, Bergisch, Germany) was added to the suspension before the cytometry analysis. Ten thousand cell per sample were collected in a MACSQuant-VYB (Miltenyi Biotec, Surrey, UK). Data analysis was carried out by using the FlowJo software.
ROS Measurements CellRox Green and MitoSOX (Molecular Probes, Carlsbad, CA, USA) were added to a final concentration of 5 µM during 30 and 10 min, respectively. Then, cells were washed with warm PBS and detached with accutase and resuspended in HBSS (Gibco, Life Technologies) for flow cytometry. Cells were fixed with 4% paraformaldehyde for 10 min at room temperature, then washed with PBS and mounted with Prolong Gold antifade reagent with DAPI (Invitrogen, Carlsbad, CA, USA). For the cytometry experiments, 10,000 cells per sample were analyzed in a MACSQuant-VYB. Data analysis was performed by using FlowJo software. Image acquisition was carried out on a microscope Nikon Eclipse 90i fluorescence microscope.
Mitochondrial Membrane Potential Measurement of mitochondrial membrane potential was performed by using a MITO-ID Membrane potential detection kit (ENZ-51018) following the manufacturer's protocol (Enzo Life Sciences, Farmingdale, NY, USA). After incubation, cells were collected, washed with PBS. Then samples were preincubated in 500 µL of the assay solution containing 5 µL of MITO-ID MP detection reagent for 15 min. Finally, 10,000 events per sample were collected in a MACSQuant-VYB and analyzed using FlowJo software.
Mitochondrial Network Mitochondrial network localization was studied after incubation of cells with a MitoTracker DeepRed FM (200 nM, Molecular Probes) at 37 • C for 30 min. After that, cells were washed twice with PBS solution and fixed with 4% paraformaldehyde for 10 min. Subsequently, cells were permeabilized with 0. 1% Triton X-100 and blocked with 1% BSA. , Then, staining with Alexa Fluor 488 phalloidin was performed following the manufacturer's instructions. Finally, samples were mounted using Prolong Gold antifade reagent with DAPI. Confocal images of mounted samples were acquired using an inverted microscope, using a 63× lens and equipped with LSM 880 with an Airyscan detector controlled by Zeiss Zen Black software.
(H) OCR was determined in MiaPaCa-2 cells treated with 10 µM TFP when cells were challenged to UK5099, Etomoxir, and BPTES (inhibitors of glucose oxidation, glutaminase, and carnitine palmitoyl-transferase 1A, respectively). Total RNAs were extracted to monitor the mRNA level of genes involved in the Krebs cycle (I) and glycolysis (J) using qRT-PCR (fold-change compared with untreated cells). For each treatment, statistical significance is * p < 0. 05, ** p < 0. 01, *** p < 0. 001, and **** p < 0. 001 compared with untreated cells (Student's 2-tailed unpaired t-Test). Data represent mean ± SEM, n = 3 (with technical triplicates).
(E) Lactate release, (F) glucose uptake, and (G) glutamine uptake were measured in the extracellular medium after 24 h in culture in TFP and non-treated cells. (H) OCR was determined in MiaPaCa-2 cells treated with 10 µM TFP when cells were challenged to UK5099, Etomoxir, and BPTES (inhibitors of glucose oxidation, glutaminase, and carnitine palmitoyl-transferase 1A, respectively). Total RNAs were extracted to monitor the mRNA level of genes involved in the Krebs cycle (I) and glycolysis (J) using qRT-PCR (fold-change compared with untreated cells). For each treatment, statistical significance is * p < 0. 05, ** p < 0. 01, *** p < 0. 001, and **** p < 0. 001 compared with untreated cells (Student's 2-tailed unpaired t-Test). Data represent mean ± SEM, n = 3 (with technical triplicates).
These results further support that EML1 may play a role in primary-cilium-related protein complexes. Simultaneously, compound heterozygous variations in RPGRIP1L (GenBank: NM_015272. 2) were identified in a patient (P700-5) with SH (Figures  3B-3D ; Table  S1 ). P700-5 also exhibited agenesis of the corpus callosum and cerebellar dysplasia (Figures  3D4  and 3D5 ; Table  S2 ). Nucleotide variations in RPGRIP1L were confirmed by Sanger sequencing. A c. 3706C>T pathogenic variation in exon 24 (R1236C, sorting intolerant from tolerant [SIFT; https://sift. bii. a-star. edu. sg/] 0. 03, damaging) was transmitted from the father. A c. 3562G>A nucleotide change in exon 22 (V1188M, SIFT tolerated) was transmitted from the mother (Figure  3C ; Table  S1 ). Since autosomal recessive mutations in RPGRIP1L have previously been associated with Joubert and Meckel syndromes (OMIM: 610937), the unusual C-terminal mutations identified here (Figure  3E ) may be important for the cortical phenotype observed.
63. 4% of the 113 proteins clearly showed expression in the VZ (8. 9% showed a CP expression only, and a further 27. 7% were of unknown expression). Cilia-related proteins were identified in both N-terminal and full-length lists (Table  S4 ), revealing a total of 42 potential cilia-related EML1 interactors. Gene Ontology (GO) analyses for the 113-protein list were performed using the DAVID (Database for Annotation, Visualization and Integrated Discovery functional annotation tool [https://david. ncifcrf. gov/home. jsp]) and STRING (Search Tool for the Retrieval of Interacting Genes/Proteins [https://string-db. org]) publicly available resources (Figure  5D ; Tables  S4, S5,  and S6 ). Cell-cell adhesion, microtubule and actin-associated proteins, and Golgi-derived protein transport were identified among other categories in DAVID GO analyses (Figure  5D ; Tables  S4  and S5 ).
This modified protein is stored in the endoplasmic reticulum (ER)-Golgi compartments when cells are incubated at 39. 5 C. Upon incubation at 32 C, the protein starts to exit these compartments and is trafficked toward the plasma membrane  (Alterio et al. , 2015; Bergmann, 1989). Using this approach combined with immunocytochemistry for the Golgi marker GM130, VSVG-EGFP anterograde trafficking was analyzed 5 and 30 min after incubation at 32 C (Figure  7B ). The presence or absence of GFP + puncta outside the Golgi apparatus was assessed at these two time points, and the number of puncta was quantified. As expected, 5 min after incubation at 32 C, most of the VSVG-EGFP protein was found within the Golgi both in WT and HeCo cells, with only some sparse GFP + puncta found in the cytoplasm (average of two puncta per cell in both conditions; data not shown; Figures  7B  and 7C ).
The annotation process was based on the latest release of the Ensembl database. Variants were annotated and analyzed using the Polyweb software interface designed by the Bioinformatics platform of University Paris Descartes and Imagine Institute. Filters used for variant screening were as follows: (i) all variants previously observed (in dbSNP138 and/or in in-house projects) were excluded; (ii) only variants leading to abnormal protein sequence (splicing, non-synonymous, frameshift, stop) were retained; (iii) we considered the PolyPhen-2 and SIFT prediction status as informative but not restrictive. Because the patient was a sporadic case from unrelated parents, the following models of inheritance in the variant screening were considered: autosomal recessive (in particular compound heterozygous but without excluding homozygous variants), X-linked and de novo SNVs.
0 mL/min over 4 min. Separation was performed on a 50 cm x 75 mm C18 column (nanoViper Acclaim PepMap<SUP>TM</SUP> RSLC, 2 mm, 100A ˚, Thermo Scientific) regulated to a temperature of 45 C with a linear gradient of 5% to 25% buffer B (100% MeCN in 0. 1% formic acid) at a flow rate of 300 nL/min over 100 min. Full-scan MS was acquired in the Orbitrap analyzer with a resolution set to 120,000 and ions from each full scan were HCD fragmented and analyzed in the linear ion trap. For identification, the data were searched against the mouse SwissProt database using Sequest HF through proteome discoverer version 2. 1. Enzyme specificity was set to trypsin and a maximum of two-missed cleavage sites were allowed. Oxidized methionine, N-terminal acetylation, and carbamidomethyl cysteine were set as variable modifications.
05. A R 1. 5 fold-change and R 3 peptides/protein were used as criteria to obtain a list of EML1 interacting partners (240). Further filtering was performed (nucleic acid-associated proteins) refining the list of EML1 protein partners (113). Additionally, to check for the specificity of the list of proteins obtained, we used the CRAPome (Contaminant Repository for Affinity Purification, www. crapome. org), a depository that contains multiple negative controls from mass spectrometry experiments allowing to query the specificity of the proteins obtained in MS results  (Mellacheruvu et al. , 2013). Only 3. 3% of the proteins were recognized as frequently found in the CRAPome data base, which ensures the specificity of the protein list.
Images were acquired with a Celldiscoverer 7 microscope (Zeiss). Shmir Design and RT-qPCR pCAGMIR30-shRNA (Addgene) scrambled and pCAGMIR30-shRNA Vcip135 were designed with the siRNA Wizard tool (Invivogen), sequences are respectively: 5 0 TTGTGCCTCAGGACCTTATTA 3 0 and 5 0 TCCTAATTTCCGTGTGACAGT 3 0. Total RNA samples were extracted from transfected Neuro2A cells (RNeasy protect mini kit, QIAGEN). First-strand cDNA was synthesized using oligo (dT) and the Superscript III Reverse Transcriptase kit (Invitrogen). Gene-specific primers were designed by KiCqStart SYBR green primers (Sigma Aldrich, primer set 1). The cyclophilin B (Ppib, peptidylpropyl isomerase B) and prosaposin (Psap) genes were used for normalization (geometric mean). Real-time qPCRs were performed using the SYBR green method, following MIQE guidelines  (Bustin et al.
QUANTIFICATION AND STATISTICAL ANALYSIS En Face Imaging Images were acquired with a 0. 17 mm z stack depth. At least two randomly-chosen ROIs (100 3 100 mm) were analyzed per embryo, and the analyzed images had a total depth of 1 mm. Images were analyzed using the ImageJ plugin Tissue Analyzer  (Aigouy et al. , 2010)  and the publicly available software Cell Profiler  (Lamprecht et al. , 2007) , a method previously described in  Foerster et al. , 2017.
ACKNOWLEDGMENTS We thank  Dr. M. Nosten-Bertrand  for advice with statistical analyses and  Dr. M. Stouffer ,  Dr. S. Bizzotto ,  Dr. A. Andreu-Cervera ,  G. Martinez Lorenzana , and  A. Muzerelle  for experimental help. We thank  G. Arras  from the  LSMP  for his assistance in MS data analysis and  Dr. A. Houdusse  for her advice. We thank  Dr. A. Shihavuddin  for his help with en face imaging data analysis. We are grateful to the following people for kindly gifting us materials and sharing protocols:  Dr. C. Delevoye  ( TGN46  antibody),  Dr. B. Goud  (VSVG-GFP construct),  Dr. A. Baffet  ( RPE1  cells and neuronal progenitor cell culture),  Dr. V. Marthiens  (neuronal progenitor cell culture),  Dr. X. Zhang  ( FLAG-VCIP135  construct),  Dr. M. Richards  and  Dr. R. Bayliss  (Strep-YFP-EML1 construct),  Dr.
A. U. , D. M. R. , A. H. , and F. F. are associated with the  BioPsy Labex  project and the  Ecole des Neurosciences de Paris Ile-de-France (ENP)  network. Our salaries and labs were supported by  Inserm ;  Centre National de la Recherche Scientifique (CNRS) ;  Sorbonne University ;  French Agence National de la Recherche  ( ANR-13-BSV4-0008-01  and  ANR-16-CE16-0011-03  to F. F. and N. B. -B. ); Fondation Bettencourt Schueller  (F. F. ); the  European Union  ( EU-HEALTH-2013 , DESIRE, number  60253  to F. F. and N. B. -B. ); the  ERA-Net NEURON JTC 2015 Neurodevelopmental Disorders program  affiliated with the  ANR  (for  NEURON8-Full-815-006 STEM-MCD  to F. F. , N. B. , and J. L. ); the  Fondation Maladies Rares/Phenomin  (project  IR4995  to F. F. ); the  European Cooperation in Science and Technology (COST Action   CA16118  to G.
M. S. M. , N. B. -B. , and F. F. ); and the  Hector Foundation II  (to J. L. ). This project was further supported by the  French ANR  under the frame of E-Rare-3, the  ERA-Net for Research on Rare Diseases  ( ERARE18-049 ). A. U. received an  ENP  PhD grant and a  Company of Biologists  travel grant and was also funded by the  Fondation de France  ( Prix Valerie Chamaillard , selected by the  Fondation Francaise pour la Recherche sur l'Epilepsie). D. L. was supported by  Region Ile-de-France  ( 2013-2-EML-02-ICR-1 ) and  Fondation pour la Recherche Medicale  ( DGE20121125630 ) grants.
Study design and population The ToyBox-study aimed to develop, implement and evaluate the effectiveness of a kindergarten-based, family-involved intervention (assessment of children"s snacking behaviour including salty and sweet snacks, and beverage consumption) in preschool children applied in six European countries (Belgium (Flanders), Bulgaria, Greece, Germany, Poland and Spain). The design and methodology of the ToyBox-study is described elsewhere  [13] [14] [15]. Data for the current analysis were obtained from the ToyBox reproducibility and relative validity studies, prior to the ToyBox-intervention. These studies were performed among pre-schoolers aged 4-6 years from different socioeconomic levels randomly selected. The studies took place between September and October 2011 in each of the six participating centres.
Validity was determined by measuring the agreement of the FFQ food group estimates with FR estimates averaged across three consecutive predefined food records/days obtained for each child participating (or two in some occasions). One of the 3 days was a weekend day and the rest two week days. Therefore, two possible combinations for data collection existed: 1. Sunday, Monday and Tuesday or 2. Thursday, Friday and Saturday. The food diaries were distributed on the day of the FFQ collection. Finally, the teacher collected the envelopes with the completed FR the agreed day (arranged between investigator, teacher and proxies within a period of 7 or 14 days after the administration) and gave them to the investigator. A C C E P T E D M A N U S C R I P T 8 In the reproducibility study, 30 to 50 participants should be recruited per country, and finally in total, 196 participants were included in the analysis, providing one complete FFQ1 and one complete FFQ2, of 326 recruited participants.
Statistical methods Statistical analyses were performed using the Predictive Analytics SoftWare (PASW, version 20; SPSS Inc. , Chicago, IL, USA). Means and standard deviations (SD) were A C C E P T E D M A N U S C R I P T 11 calculated for food consumption estimates obtained from FFQ1, FFQ2 and FR (for single and aggregated food groups). Crude data was log-transformed (log n ) to improve normality for all the 37 food groups. No cases were found and subsequently no cases were excluded from this analysis on the basis of being rarely consumed (< 5%) or due to incompleteness (participants with 25% of missing values in the FFQ1 and FFQ2). Pearson productmoment correlation coefficients for log-transformed values were calculated to assess the reproducibility of FFQ1 compared to FFQ2. Spearman"s rank correlation coefficients (Spearman´s rho) for log-transformed values were calculated to assess the validity of the FFQ compared to FR.
2 e also excluded patients without complete information on cardiovascular risk factors necessary for ASCVD risk calculation or those who were on statins or other lipidlowering therapies at baseline. Race/ethnicity was self-reported (83. 2%) or inferred (16. 8%) based on the Social Security Record database as previously described. 22 The study sample included NHWs, African Americans, Asians, and Hispanics. Asians were disaggregated into Chinese, Asian Indian, Filipino, Japanese, Korean, Vietnamese, and other Asians. Based on US Census categories, Hispanics were disaggregated into Mexican, Puerto Rican, Cuban, and other Hispanics. Because of small sample size (n=223), Cubans were combined with other Hispanics.
Prediction of ASCVD Risk Based on Pooled Cohort Equation and Recalibration The 5-year ASCVD predicted risk was calculated for adults between ages 40 to 79 using the published parameter estimates from the PCE. 2, 20 We used the parameters developed for NHWs to estimate predicted values for Asian and Hispanic populations. The 5-year predicted risk values were adjusted to reflect varying follow-up time, assuming proportional hazard, which was validated in our data (global test of proportional v 2 (11)=0. 115 and plotting of Schoenfeld.