dataesr/scientific-paragraphs-categorization huggingface dataset:
All procedures were performed under general anaesthesia and two-or three-dimensional TOE guidance. Some cases were guided by fusion between echocardiography and fluoroscopy (Echonavigator software®, Phillips)  [21]. All procedures were performed by experienced operators and/or with the support of highly trained operators for pmVSD closure. Short 5F and 6F sheaths were introduced in the femoral artery and femoral vein, respectively. Intravenous heparin (50-100 IU/kg according to the institutional protocol) was given. An angiogram was performed in the left lateral view to measure the VSD. The defect was crossed retrogradely from the arterial route using a multipurpose catheter or a cut pigtail and an exchange guidewire, which was snared in the right side (pulmonary artery or superior vena cava) to create an arteriovenous loop.
New devices for this indication are under investigation and will need to be carefully assessed. The optimal therapeutic strategy in this selected population remains to be determined in the modern arena. Therefore, the French heart association started the FRANCISCO study (Observatoire français des Communications Interventriculaires périmembraneuses Congénitales avec hyper débit pulmonaire, NCT03363932) to investigate the long-term outcome of these patients according to therapeutic strategy and assess anatomic predictors of complications.
Data collection, structure determination and refinement. X-ray diffraction data were collected at 100K using beamlines Proxima-1 and Proxima-2 at the Soleil synchrotron (GIF-sur-YVETTE, France). Both data sets were processed using XDS 38 and AIMLESS from the CCP4 suite  39. The crystal structures were solved by molecular replacement using Phaser  40  and a single monomer of the PDB 3ZIE as a search model. All structures were refined through several cycles of manual building with COOT  41  and reciprocal space refinement with BUSTER  42. The Supplementary table  1  shows the crystallographic statistics. Structural figures were generated using Chimera 43. Atomic coordinates and structure factors can be found in the protein data bank under the accession codes 7AL1 and 7AL2.
The KaleidaGraph software was used to fit the K x to the experimental data. We used a FP-8200 (Jasco, Tokyo, Japan) spectrophotometer equipped with a thermostatic Peltier ETC-272T at 25 °C. Experiments were performed in a high precision cell cuvette made of Quartz with a light Path of 10x 4 mm (Hellma, France). A bandwidth of 5 nm was used for emission and excitation. 1 µmol L -1 of peptide was used in Titration buffer (100 mmol L -1 KCl and 25 mmol L -1 Hepes at pH 7. 4). We measured the florescence emission between 300 and 400 nm at a scan rate of 125 nm min-1 with an excitation wavelength of 280 nm. The obtained spectra were corrected by blank subtraction (SUV light scattering in titration buffer). Next, the maximum wavelength value (λ max ) was calculated to measure the partition coefficient (K x ).
Raw images are composed of fifteen images per plane per channel (five phases, three angles), and acquired with a Z-distance of 0. 10 µm. Acquisition parameters were adapted from one image to one other to optimize the signal to noise ratio. SIM images were processed with ZEN software (Carl Zeiss, Germany) and then corrected for chromatic aberration using 100 nm TetraSpeck microspheres (ThermoFisher Scientific) embedded in the same mounting media as the sample. For further image analysis of SIM image z stacks we used Fiji (ImageJ) Version 2. 0. 0-rc-68/1. 52i. Namely, we assigned a color to the fluorescent channel, stacks were fused to a single image (z projection, maximum intensity), stacks were rotated 90°(resliced) prior z projection for the side view, and videos were created via 3D projection.
Morphometric and fluorescence measurements. 2 µL of immunolabelled M. smithii cells solution together with 1 µL of Vectashield (Vector Labs) were applied to an 1 % (w/v) agarose covered microscopy slide and imaged using a Zeiss Axioplan 2 microscope equipped with an Axiocam 503 mono camera (Carl Zeiss, Germany). Epifluorescence images were acquired using the ZEN lite software (Carl Zeiss, Germany) and processed using the public domain program Fiji (ImageJ) Version 2. 0. 0-rc-68/1. 52i in combi-nation with plugin MicrobeJ Version 5. 13l. The cell outlines were traced and cell length, width fluorescence intensity along the cell length and presence of fluorescent maxima were measured automatically. Automatic cell recognition was manually double-checked. For the mean fluorescence intensity plots cells were automatically grouped into four classes according to the detected FtsZ (0-3 fluorescent maxima detected) and the corresponding FtsZ and SepF mean fluorescence intensity of each group was plotted against the normalized cell length.
Sequence analysis. FtsZ sequences from either Archaea or Bacteria were aligned with MAFFT using the L-INS-i algorithm  44. Only the Cterminal domain of FtsZ was kept and after several cycles of trimming and realigning, the aligned FtsZ CTD was uploaded to https://weblogo. berkeley. edu/logo. cgi to create the WebLogo  45. For structure-based SepF alignment, representative sequences from Bacteria and Archaea were manually chosen. Sequences where aligned using T-Coffee  46. Graphical representation was made using ENDscript server  47. For secondary structure prediction, sequences were aligned using MAFFT with the L-INS-i algorithm  44  and secondary structures were detected using Ali2D  48. Figures were compiled using Illustrator 2020 (Adobe Systems Inc. USA).
Distribution, phylogeny, and synteny analysis. A customized local genome database was compiled for 190 Bacteria and 150 Archaea representative of all major phyla in NCBI (as of January 2020). The presence of FtsZ, FtsA and SepF homologues was assessed by performing HMMbased homology searches using custom made HMM models and the HMMER package  49, 50  (default parameters). Separate searches were carried out with archaeal and bacterial queries and absences were checked with TBLASTN 51 or individual HMMER searches against all available taxa in NCBI corresponding to those phyla. Results were mapped onto the bacterial and archaeal reference phylogenies using iTOL  52. For phylogenetic analysis, FtsZ, FtsA and SepF homologues were aligned using MAFFT (L-INS-i algorithm)  53. Columns with excess gaps (>80 % for FtsA/SepF, >70 % for FtsZ) were removed with trimAl  54.
HMM profiles were created for the families containing members of three or more archaeal lineages using the HMMER package  50. The families were annotated manually by using BLASTP v2. 6. 0  51  and the Conserved Domain Database from NCBI  59. Mac-SyFinder  60  was then used to identify, in each archaeal taxon, clusters containing at least three genes with a separation no greater than five other genes.
Acknowledgments. This work was partially supported by grants from the  Institut Pasteur (Paris) , the  CNRS (France)  and the  Agence Nationale de la Recherche  ( PhoCellDiv ,  ANR-18-CE11-0017-01  and  ArchEvol ,  ANR-16-CE02-0005-01 ). N. P. is supported by a  Pasteur-Roux Postdoctoral Fellowship  from the  Institut Pasteur (Paris). A. S. and D. M. are part of the  Pasteur -Paris University (PPU) International PhD Program , funded by the  European Union 's  Horizon 2020 research and innovation program  under the  Marie Sklodowska-Curie  grant agreement No  665807. M. G. acknowledges support from  Programa de Desarrollo de las Ciencias Básicas  and  Agencia Nacional de Investigación e Innovación, Uruguay. We thank  A. Chenal  help with the lipid interaction studies. We gratefully acknowledge the core facilities at the  Institut Pasteur   C2RT ,  A.
Haouz ,  P. Weber ,  C. Pissis  (PFC). We thank the staff of the synchrotron SOLEIL for assistance and support in using beamlines PX1 and  PX2. We thank  A. Salle  for help with the 3D SIM. We gratefully acknowledge the  UTechS Photonic BioImaging (Imagopole) ,  C2RT ,  Institut Pasteur (Paris, France ) as well as the  France-BioImaging infrastructure network  supported by the  French National Research Agency  ( ANR-10-INSB-04 ; Investments for the Future), and the  Région Ile-de-France  (program  Domaine d'Intérêt Majeur-Malinf)  for the use of the Zeiss LSM 780 Elyra PS1 microscope. We acknowledge technical assistance by  Barbara Reischl.
Study participants and human serum samples To investigate the relationship between dietary Neu5Gc and circulating anti-Neu5Gc antibodies in humans, we used the well-established NutriNet-Santé cohort (Clini-calTrials. gov # NCT03335644). This is a French webbased cohort study launched in 2009 with the objective to investigate the relationship between nutrition (nutrients, foods, dietary patterns, physical activity), health and diseases (e. g. , cancer, cardiovascular diseases, metabolic syndrome, rheumatoid arthritis, and hypertension), and determinants of dietary behaviors and nutritional status  [19]. At baseline and every 6 months, participants completed three non-consecutive validated web-based 24-h dietary records, randomly distributed between week and weekend days to take into account intra-individual variability, in which they declared all foods and beverages consumed during periods of 24 h.
Quantification of Neu5Gc in food items Neu5Gc content in French food items was measured by DMB-HPLC. All the food items containing animal products among the 3500 food items of the NutriNet-Santé food composition table were identified. Among them, Neu5Gc data were not available for 10 food items (roasted horse meat, horse steak, roasted deer, roasted doe, kid, roasted kid, roasted buffalo, Antwerp filet, mixed mince, and potjevleesch), originated from horse, buffalo, doe, and goat. These 10 food items had been consumed at least once by 6 participants among the 120 selected cohort. For these food items, a value resulting from the mean of the Neu5Gc content of beef and lamb was computed. Thus, food sources of Neu5Gc included meat (cow, lamb, goat, pig, rabbit, and bush meats) and dairy (cow, sheep, buffalo, and goat).
Calculation of individual's daily Neu5Gc intake We used 19,621 participants enrolled between May 2009 and May 2015 in the NutriNet-Santé study, and the total amount of dietary Neu5Gc intake (μmol/day) was computed for each participant using all the available data on 24-h dietary records for each food source. Hence, for all available 24-h dietary records, food items containing Neu5Gc were identified (meat from cow, lamb, goat, pig, rabbit, horse, buffalo, doe, and goat; dairy from cow, sheep, buffalo, and goat), and a mean daily intake for each food item (in g/day) was computed for each participant. For this purpose, French recipes validated by food and nutrition professionals were used to assess the amounts of simple food items containing Neu5Gc (see the list above) consumed by the participants from composite dishes obtained through the 24-h dietary records.
Statistical analyses As nutritional habits and intakes vary across gender, we computed statistical analyses by gender. Apart from total Neu5Gc intakes, three additional classes of dietary Neu5Gc sources were computed: Neu5Gc from meat, Neu5Gc from dairy cow, and Neu5Gc from dairy sheep and goat. Sex-specific tertiles for dietary Neu5Gc intakes were computed for each class (total daily Neu5Gc intake and daily Neu5Gc intake from meat, from dairy cow, and from dairy sheep and goat combined). Statistical analyses were performed by SAS 9. 4®. Quantitative variables presented as means ± standard deviation (SD) or means ± standard error of the mean (sem) if normally distributed, or as medians (25th-75th percentiles) if not normally distributed, while qualitative variables were presented as percentages.
Results International colorectal cancer (CRC) and red meat intake correlate in different nations While many epidemiological studies support increased cancer risk with high meat intake, we wanted to explore this relationship at the national level, based on the available global national meat consumption and cancer risk data. Dietary habits can vary dramatically in different parts of the world  [32]. To evaluate the effect of red meat intake on CRC in different world nations, national per capita meat intake from the Food and Agriculture Organization (FAO) of the United Nations, FAOSTAT database  [33] , and CRC age-standardized incidence and International CRC age-standardized incidence and mortality rates (ASR per 100,000 person-years, including colon, rectum, anus cancers) in individuals aged 45-69 from GLOBOCAN  [34]  and international per capita meat intake from FAOSTAT  [33]  (including bovine, mutton, goat and pig; excluding poultry and aquatic mammals; Additional file 2: Data file S1).
b Distribution of CRC incidence (Pearson r = 0. 8482) and mortality (Pearson r = 0. 7249) per nation of the highest and lowest meat intake quartiles (n = 38 each) strongly correlates (both p < 0. 0001). c CRC incidence and mortality per nation of the highest and lowest quartiles of meat consumption (n = 38 each) divided by gender show a strong correlation in nations with high levels of meat intake (Kruskal-Wallis test, **p < 0. 0049 and ****p < 0. 0001, respectively), but not in nations with low levels of meat intake mortality rates from GLOBOCAN database  [34]  were extracted (Fig. 1 ; Additional file 2: Data file S1). Both CRC incidence and mortality positively correlate with meat intake (Fig. 1a ). CRC rates were lowest in Sri Lanka, India, and many African nations, while highest in Australia, USA, Europe, and South American nations (Additional file 2: Data file S1), showing dramatic differences between the highest and lowest meat intake quartiles (Fig.
Acknowledgements The authors warmly thank all the volunteers of the NutriNet-Santé cohort. We also thank  Nathalie Druesne-Pecollo  (operational coordinator);  Younes Esseddik ,  Thi Hong Van Duong ,  Régis Gatibelza , and  Jagatjit Mohinder  (computer scientists);  Cédric Agaesse (dietitian) ;  Julien Allègre ,  Nathalie Arnault , and  Laurent Bourhis  (data-managers/biostatisticians); and  Fatoumata Diallo, MD , and  Roland Andrianasolo, MD  (physicians) for their technical contribution to the  NutriNet-Santé study. We also thank  Ludmilla Le Berre  (engineer) for organizing the sample shipment between Nantes and  Tel Aviv University , and  Mor Semo  for the assistance in DMB-HPLC analysis of food samples. Chimpanzee sera were obtained from the local zoo only during routine maintenance procedures and kindly provided by  Dr.
Funding This work was supported by the  Israel Ministry of Science & Technology  (S. B. and V. P-K. ), and by the  European Union   H2020 Program  grants ( ERC-2016-STG-716220 ) (to V. P-K. ). The  NutriNet-Santé study  was supported by the following public institutions:  Ministère de la Santé ,  Santé Publique France ,  Institut National de la Santé et de la Recherche Médicale (INSERM) ,  Institut National de la Recherche Agronomique (INRA) ,  Conservatoire National des Arts et Métiers (CNAM) , and  Université Paris 13  (to P. G. ). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
The samples were measured in quartz cells (Hellma) of 0. 01 mm path length for MA, which had the highest protein concentration, and 0. 1 mm path length for MI, FLAG, and CYL. Three consecutive spectra were recorded and averaged using a 1 nm resolution step and a 200 nm/min scan rate. The data were reduced using the CDTool software. 18 mall-Angle Scattering. Small-angle X-ray scattering (SAXS) was recorded at the Bio-SAXS beamline ID14-3 at the ESRF (Grenoble). Each sample of the dilution series was gently pipetted into separate wells of a standard 96 well plate, sealed with Cristal tape. The samples were transferred to the measuring point, a quartz 1 mmdiameter capillary, using a modified HPLC pump system. 19 Between each sample, the capillary, syringe, and connecting tubing were flushed clean with 12 M urea solution before rinsing with milliQ water and drying.
The SAXS was recorded for the water solution between each silk sample to confirm that the capillary was thoroughly clean before the next measurement and that no residue of silk was left following the cleaning step. The SAXS data were collected using a Pilatus 1 M X-ray detector at a fixed sample detector distance of 2. 43 m and incident radiation wavelength of 0. 93 Å, giving an accessible q range of 0. 05-5. 8 nm -1. 19 A test was made to estimate when radiation damage of the silk proteins might be significant. At data collection exposure times greater than 5 s, evident changes were observed in the SAXS pattern. For this reason, exposure times were kept to a maximum of 1 s, and multiple exposures (up to 50 frames per sample) were taken while continuously flowing the sample through the capillary using a minimum flow rate of 0.
5 μL/s to additionally avoid radiation damage. At these flow rates, we did not observe any orientation in the 2D scattering patterns and concluded that there was no significant effect of shear or extension. The data were reduced using the ID14-3 data reduction pipeline  19  with bovine serum albumin serving as a calibration standard for M w. The obtained three-column Ascii files for up to 50 frames per sample were averaged using PRIMUS  20  after the exclusion of anomalous data due to empty capillary or bubbles in the sample. Time-of-flight small-angle neutron scattering (SANS) measurements were conducted at SANS2d, ISIS Facility, U. K. On SANS2d, the collimation can be optimized for the sample-to-detector distance, which in these experiments was 4 m. By selecting 1. 75 to 16. 5 Å wavelength neutrons, the q range is 0.
004 to 1. 5 Å -1 , recorded by a single 0. 96 m2 Ordela 21000 N detector. Complementary SANS measurements were performed at the D11 beamline at the Institut Laue Langevin (ILL). The energy was set to 6 Å and the sample was scanned at 2, 10, 28 m sample detector distances. The samples were prepared in the same manner as for the SAXS measurements with degassed milliQ water as the solvent. As the main spider silk glands are duplicated in a spider, both glands were used to prepare a single stock solution. Further dilution was also with milliQ water. 400 μL of each sample was prepared in this way and sealed in quartz standard Hellma cells of 1 mm path length. The cells were placed in a thermostated and automated sample changer at 20 °C. Small-angle neutron scattering data were collected for 15 min from each sample, and the process was repeated until sufficient signal-to-noise ratios were achieved, with typical collection times ranging from 30 min to 2 h depending on the protein concentration.
During the SAXS measurements, the sample was static unlike the SAXS samples. In this manner, instabilities or changes in the sample could be monitored. The neutron scattering contrast came from the inherent scattering length density difference of protein to water with no additional contrast variation using deuterium exchange. All data reduction and background subtraction were made using Mantid (http://dx. doi. org/10. 5286/software/mantid). The scattering from a partially deuterated polymer standard allowed data to be normalized to absolute intensities. Data Analysis. Both SAXS and SANS data were initially interpreted by applying the Guinier approximation using PRIMUS. 20 rom a plot of (ln I(q) vs q 2 ), the slope can be used to determine the radius of gyration (R g ). The projected y-intercept yields the intensity at q = 0 nm -1 , I(0), which can be used to calculate the molecular weight, M w , of the scattering entity.
The p(r) function or distance distribution function describes the distances between points within an object. In a protein ensemble, this proves to be useful for visualizing conformational changes as small changes in the relative positions of a few residues can be resolved in the shape of the p(r) distribution. The p(r) function obtained by two methods were compared: by the indirect Fourier transformation method (using GNOM  21  ) and by Bayesian statistics (BayesApp  22  ). In principle, the advantage of the Bayesian statistics over GNOM is that the maximum dimension of the scattering object (D max ) is estimated from the program with no user constraints. In contrast, in GNOM, the standard settings were chosen for p(r), and D max was estimated visually from the fit 23 using a q max of 0. 4 nm -1.
Patients and Methods Patients and tumor samples. One hundred seventy-six (176) primary lung cancer specimens that have been prospectively collected and stored frozen the time of surgery from October 2011 to December 2014, were available for the purpose of the present study. Surgery was performed for curative intent and clinical and survival data were collected in electronic medical records. Of the initial collection of 176 samples, 4 samples corresponding to patients with stage IV NSCLC, and 3 samples with surgically related death were excluded, and 4 samples were excluded for technical reasons. Therefore, 165 subjects were included in the study.
Mutational analysis. Samples were characterized for molecular alterations by targeted NGS (Ion Ampliseq Colon-Lung Cancer Research Panel V2, Life Technologies). Briefly the multiplex barcoded libraries are generated from 10 ng of DNA following manufacturer's recommendations (Ion Ampliseq Library Kit V2) and are normalized using the Ion Library Equalizer Kit. The pooled libraries (max 96) are processed on Ion Chef System for template preparation and chip loading (Ion Pi Hi-Q Chef Kit, Ion Pi Chip V3), and sequenced on the Ion Proton System (Life Technologies). The FASTQs sequencing data are aligned to the human genome (hg19) and processed using Iontorrent Suite V5. 0. 4. 0 This package included the Torrent Variant Caller V5. 0. 4. 0 using the built-in "Somatic -low stringency" with optimized parameters to automatically call variants with allelic ratio>2%.
One of the dye colors (Genescan Rox 400 Hd size standard, Applied Biosystems, red) is used to detect a labeled size standard present in each sample. Fragments and ROX 400 HD are mixed with HiDi Formamide (Applied Biosystems) prior to capillary electrophoresis. (3) The data are analyzed using Genemapper Software to determine the relative size of each dye-labeled fragment in the sample.
In each run, normal human lung RNA as described above was used as calibrator. Intratumor CHOP transcripts expression. CHOP Transcripts were quantified using SYBR green (CHOP) on an ABI Prism 7900 sequence detector system (Applied Biosystems). Measures were made in triplicates with 10 ng/μl of cDNA using Taqman Gene Expression Assay Master Mix (Applied Biosystems). Real-time PCR data for CHOP were presented as individual data points, and reported as expression levels (cycle thresholds, Ct) referred to as an internal control. Therefore, Ct are calculated as (Ct gene of interest -Ct internal control). Transcripts expression levels were presented as 2 -ΔCT as recommended by  27.
Discussion Our work demonstrates for the first time that in a cohort of patients with NSCLC, intra-tumor IRE1 splicing activity of XBP1 mRNA may impact tumor phenotypes and outcomes. Therefore, monitoring intra-tumor IRE1 activity appears as a valuable biomarker for predicting cancer aggressiveness, and could help tailoring pharmacological strategies targeting IRE1 activity. Indeed, several functional studies have shown that targeting the expression or the RNase activity of IRE1 reduces the progression of various forms of cancer mostly due to ablating the prosurvival effects of XBP1 on tumor growth  9, 14, 32. Importantly, we provide evidence that measuring the levels of sXBP1 transcripts in tumors by using a fully automatable genetic method based on fragment analysis is clinically relevant, this especially as the expression of sXBP1 is not easily captured by classical transcriptomic platforms for technical reasons (except maybe in public RNAseq datasets using high read depths), and, therefore, the clinical relevance of XBP1 splicing in cancer development and progression has not been specifically addressed.