dataesr/scientific-paragraphs-categorization huggingface dataset:
Confocal laser scanning microscopy analysis was performed using a FluoView FV10i system (Olympus). Endotoxemia-Female littermates 8 weeks or older were injected intraperitoneally with freshly prepared LPS (30 mg/kg; Escherichia coli 0111:B4; Sigma-Aldrich) in normal saline. Survival and righting reflexes were monitored every 12 h for 5 days, after which all surviving mice were sacrificed. Experimental animals without righting reflex at time of monitoring were considered moribund and were euthanized and included as nonsurvivors in survival curves generated by the Kaplan and Meier method using GraphPad Prism software. Plasma Cytokines-Blood from the retro-orbital venous plexus was collected with EDTA-coated glass capillaries into EDTA tubes 8 h after intraperitoneal challenge with 30 mg/kg LPS.
3B ). Further, cyclooxygenase-2 (COX-2), a key downstream inflammatory gene, was also induced to a similar extent in BMDMs from Sphk2 Ϫ/Ϫ , M⌽ Sphk dKO, and WT mice 24 h after LPS treatment (Fig. 3C ). Similar findings were seen in thioglycolate-elicited peritoneal macrophages (data not shown). We also treated BMDMs with LPS for 2 and 6 h, and mRNAs involved in the inflammatory response were detected by qPCR. The results indicate that IL-1, IL-6, and TNF␣ mRNA were induced by LPS treatment, but no significant differences were observed among BMDMs from Sphk2 Ϫ/Ϫ , M⌽ Sphk dKO, and WT mice (Fig. 3D ). Macrophage Sphk1 and 2 Are Not Necessary for Inflammatory Responses in Vivo-Next, to investigate the role of myeloid Sphk isoenzymes in inflammatory responses in vivo, we employed LPS to model the systemic inflammatory response characteristic of septic shock.
By considering the subsets' complements, it is clear that C(16, 16c) = C(  16, c ) is also the number of subsets with 16c 1-points. The developed method determines the non-isometric finite subsets of points that can be constructed by starting from the vertices of a unit hypercube. This method consists of computing the group of isometries of the unit hypercube in R 4 and using this group to ignore the subsets of points that differ by the isometries of 4dimensional space. Proposition 7 in  [21]  proves that an algorithm of this type returns the discrete cells in Z 4. A scheme of this algorithm is shown in Fig. 3. [4] ] in the Mathematica package Combinatorica' gives a list with the 384 permutations of vertices that leave the unit hypercube invariant. Each of these permutations corresponds to an isometry of the unit hypercube.
Conclusions In this paper, we have shown a computational method that (1) determines the discrete cells in the space Z 4 and (2) embeds these cells into R 4. By running Algorithm 1 in the symbolic computation package Mathematica, 402 discrete cells contained in the unit hypercube were obtained. These 402 discrete cells are embedded in the space R 4 and the convex hulls are computed using Algorithm 2. Note that 347 of these embedded cells are full-dimensional cells of dimension 4 (cf. the second column of Table  3  in  [1] ). These 402 embedded cells are saved in a look-up table. By combining the cells of the look-up table, a continuous convex analog for a given 4-dimensional digital object can be constructed. More concretely, the procedure for constructing the cell complex consists of these three steps: (1) associate each of the points of the image with a discrete cell; (2) construct the embedded cells from the discrete cells; and (3) invert the isometry between each subset of points of the image and its associated discrete cell.
Birth attendants in each unit prospectively identified all deliveries with PPH and reported them to the research team. In addition, a research assistant reviewed the delivery suite logbook of each unit and checked any available computerized patient charts. For every delivery with a mention of PPH, the patient's obstetrics file was further checked to verify the PPH diagnosis. During the data collection period, 6660 cases of PPH occurred among 146,781 deliveries in the 106 maternity units for a total incidence of 4. 5% of deliveries. During the same period, a representative sample of women with deliveries without PPH in the same units was recruited by a random selection of 1/60 of deliveries (ratio based on an estimated incidence of severe PPH of 1/60), to serve as controls in a variety of studies such as this one.
Because of the specificities of labor and delivery among primiparas, we performed the same analysis in this subgroup of low-risk primiparas. Based on our sample size of 4477 women with PPH (and 1125 with severe PPH) and 1744 controls, and an exposure prevalence of 5% among controls, we estimated that the power of the study would be 100% to detect an OR of 2 and 95% to detect an OR of 1. 5 for all PPH, and 100% to detect an OR of 2 and 75% to detect an OR of 1. 5 for severe PPH. Analyses were performed with Stata v. 11 software (Stata Corporation, college station TX, USA). Individual consent was not needed in this study. Collective information about the study was provided in all maternity units and women had the possibility to deny the use of data from their medical files. The principle of non-opposition was applied.
Discussion We found that induction of labor was independently associated with a 20 % higher risk of PPH and severe PPH in low-risk parturients, regardless of the method of induction used. This excess risk of PPH and severe PPH was significant for standard but not for non-standard indications. Our study design had several strengths. Although the data were extracted from a cluster-randomized trial, the study was population-based as it covered all maternity units in a given area and consequently all women delivering in this area and more specifically, all women with PPH; the characteristics of maternity units and parturient women were comparable to the national picture on the whole  [1] , and, in particular, for the characteristics of labor induction  [14]. Women with PPH and the control subjects were selected from the same source cohort of deliveries, which decreased the likelihood of selection bias.
The project was funded by the  French Ministry of Health  under its  Clinical Research Hospital Program  (contract no. 27-35 ) and the  Caisse Nationale d'Assurance Maladie (CNAMTS). IK was supported by a grant from l 'Institut de Recherche en SantePublique (IRESP). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Mass spectrometry imaging Twelve micrometers thick sections (from one mouse per time point) were prepared at 220uC with a CM3050-S cryostat (Leica Microsystems SA, Nanterre, France) and deposited onto silicon wafers (2uin. diameter polished silicon wafers; ACM, Villiers-Saint-Frederic, France). Before analysis, samples were dried under vacuum at a pressure of a few hectopascals for 10 min. Optical images were recorded with an Olympus BX51 microscope fitted with 61. 25 to 650 lenses (Olympus, Rungis, France) and a ColorView I camera monitored by Cell B software (Soft Imaging System, GmbH, Mu ¨nster, Germany). All ion images were recorded using a TOF-SIMS IV commercial mass spectrometer (Ion-Tof GmbH, Mu ¨nster, Germany). This spectrometer is equipped with a liquid metal ion gun delivering bismuth clusters.
The primary ion dose density (also called 'fluence') was 5610 11 ions. cm 22 , well below the static SIMS limit  [35] , ensuring little damage and high secondary ion emission for the acquisition of images of both polarities on the same area. Images of 1006100 mm 2 with a lateral resolution of 390 nm were recorded in the negative ion mode using the burst alignment mode. The experiment was performed twice on separate tissue areas. Under these conditions, the fluence was 2610 12 ions. cm 22. The data acquisition and processing software were IonSpec and IonImage (TOF-SIMS 4. 1, Ion-Tof GmbH, Mu ¨nster, Germany). Ion peak assignments were made according to mass spectra of reference compounds, and confirmed by comparison with literature  [23, 24, 27, 28, 29, 30].
This study was funded by the  ANR/PNRA  ( National program  for diet and nutrition research) project #5. 34 ABSINTE. AS was supported by a  Ph. D. research fellowship  from the  Institut de Chimie des Substances Naturelles (CNRS)  and MC received a post-doctoral fellowship from PNRA # 5. 34  ' ABSINTE '. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
To further assess the implication of autophagy in illegitimate substrate management, we measured autophagic flux in POS-exposed Sertoli cell cultures, pretreated with bafilomycin A 1 , which blocks the fusion of MAP1LC3A-II containing autophagosomes and lysosomes and inhibits their acidification. 38  of POS-exposed TM4 cells after Atg5 siRNA silencing, revealed the accumulation of POS fragments and the measurement of the phagocytosis index showed a significant increase of total number (bound + injested) of POS fragments in TM4 cells after Atg5 siRNA silencing (Fig. 6D ). Altogether, these data imply that Sertoli cells recruit autophagy for the management of ingested illegitimate (POS) but not legitimate (RB) substrates.
The area spreading by ingested substrates was obtained by subtracting the area of plasma membrane-bound particles from total area of particles bound and ingested by Sertoli cells. The area of RB and POS and the number of nuclei were counted using Mac Biophotonic Image J software. The phagocytic index was calculated as the ratio of RB or POS area/nuclei number, in each well. Statistical analysis was done using two-way ANOVA followed by Bonferroni post-hoc test. Immunocytochemistry. MAP1LC3A, myosin II, phospho-MERTK, RAC1 and activated-RAC1 immunocytochemistry was performed on fixed Sertoli cells in Labteck chamber slides. After 5 min of fixation with freshly prepared paraformaldehyde/ PBS (pH 7. 4), Sertoli cells were permeabilized for 5 min with 0. 5% Triton X-100/PBS and incubated with primary antibodies in 1%BSA /PBS; the dilution of antibodies was as follow 1:500 for anti-MAP1LC3A and 1:250 for phospho-MERTK, myosin II, RAC1 and activated-RAC1.
Omar Benzakour , ( FP7/2007-2013)  under grant agreement number  220892-PHAGOCYTOSIS : "Molecular mechanisms underlying the link between vitamin K-dependent proteins and phagocytosis of apoptotic cells during cell differentiation processes. "This work was also supported by funds from  Retina France  and from la  Ligue Nationale Contre le Cancer, region Poitou-Charentes. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Study Design Data were collected through standardized questionnaires. The investigators recorded patients' demographics, diabetes characteristics, complications, treatments and cardiovascular risk factors. The patients were then asked to report any pain they were suffering in their feet and/or legs and its duration. If the patients reported chronic pain in the lower limbs, defined as daily pain for at least three months, the investigator recorded the treatments for pain received by the patient and administered the DN4 questionnaire, the monofilament test and the MNSI (Michigan Neuropathy Screening Instrument) (see below), before finally noting the cause of pain, according to their own clinical judgment. All the patients (with and without pain) were asked to complete a series of questionnaires to assess health-related quality of life, sleep disturbances and anxiety and depression (see below).
Statistical Analysis Continuous variables, which had all a normal distribution, are described as means 6 SD; categorical variables are expressed as frequency distributions and percentages for the relevant subject groups, with 95% confidence intervals. Missing data were not considered in the expression of the results. Pain intensity scores of 1 to 3 were considered to indicate mild pain, scores of 4 to 6 were considered to indicate moderate pain, and scores of 7 to 10 corresponded to severe pain. A logistic regression model was used to identify the factors (age, sex, types of diabetes, HbA 1C level, diabetes complications, risk factors) potentially predictive of chronic pain with neuropathic characteristics. The variables significant in the univariate analysis, at a threshold of at least 20%, were entered into a septwise multivariate logistic regression model and the odds ratio for significant factors was calculated with a 95% confidence interval (CI).
One-way analyses of variance (ANOVA) were used to compare the scores for quality of life (SF-12), sleep disorders (MOS-Sleep) and mood disorders (HADS) between the various groups of patients. A logistic regression analysis was used to identify the factors (age, sex, type of diabetes, HbA 1C , complications, risk factors, pain intensity, DN4 score, MNSI-examination score, monofilament test) predictive of an altered SF-12, HADS or MOS-Sleep scores. Stepwise logistic regression models were used, as described above, to identify factors independently predictive of alterations of these scores. Data were analyzed with SAS version 9. 1 software (SAS Institute, Cary, NC, USA).
Potentiodynamic measurements Polarization measurements were performed in a thermally jacketed conventional threeelectrode Pyrex cell with a platinum foil counter electrode and saturated calomel electrode [SCE] coupled to a fine Luggin capillary as the reference electrode. All measurements were carried out using on an electrochemical measurement system (Volta-Lab 40) comprised of a PGZ 100 potentiostat, a PC and Voltamaster 5. 3 electrochemical software. The potentials were recorded at a scan rate of 1 mV/s from the corrosion potential [E corr ] in the cathodic direction and subsequently in the anodic direction. The electrode was held in the test environment for 30 min prior to each experiment, which proved sufficient for E corr to attain a reliable stable value. Corrosion current density values were obtained by Tafel extrapolation method.
Increased Turnover of Epithelial Cells in LXR Mutant Mice under High-Cholesterol Condition The identity of proliferative cells was determined by immunofluorescence analyses using markers for prostatic cells subtypes. To identify proliferative cells within the different prostatic compartments, we performed double staining for PCNA and CK18 (luminal cells), p63 (basal cells) or SMA (stromal smooth muscle cells). Most PCNA+ cells were positive for CK18 (Figure  2Aa, b,  and c ) and were surrounded by p63+ epithelial basal cells (Figure  2Ad , e and f). Occasionally, p63+;PCNA+ cells were observed (data not shown), indicating that all the epithelial lineage could be targeted by proliferation in LXR null mice fed a high cholesterol diet. PCNA+ cells were exclusively localized inside the epithelium delineated by smooth muscle actin (SMA) staining (Figure  2Ag , h and i).
In order to determine gene expression signature of the PIN phenotype in LXR mutant mice fed a high cholesterol diet and to identify relevant molecular events, we have restricted the gene list using Venn analysis. We selected common deregulated genes associated with the PIN phenotype and eliminated those that were sensitive to diet and/or LXR ablation alone. Therefore, we focused on the genes involved in the establishment of the PIN phenotype by selecting genes that were deregulated in both arrays 3 (lxr-/-normal vs. lxr-/-high chol. ) and 4 (+/+ high chol. vs. lxr-/-high chol. ) and by subtracting genes that were deregulated in both arrays 1 (+/+ normal vs. +/+ high chol. ) and 2 (lxr-/-normal vs. +/+ normal). This resulted in a list of 463 genes (Dataset S1), 253 up and 210 down (Figure  4B ).
Ingenuity Pathway Analysis (IPA) was used to investigate potential biological processes that underlay the PIN phenotype of LXR mutant mice (Figure  S4 ). The second most significantly enriched gene-category was 'cancer', which was associated with a large list of 146 genes (Dataset S2). More than 50% of these 146 genes were also deregulated in a mouse model of prostate cancer resulting from PTEN deletion in prostatic epithelium  [18]  (data not shown). This strongly suggested that the PIN lesions observed in LXR knockout mice in the high cholesterol condition were genuine precancerous alterations. Interestingly, this analysis showed downregulation of two well described prostatic tumor suppressor genes Nkx3. 1 and Msmb (Dataset S2, highlighted in red), which was further confirmed by qPCR analysis (Figure  5A , Figure  S5 ).
These two genes were specifically found in gene categories such as tumor development, cell proliferation and prostate organogenesis (Dataset S3, highlighted in red). Nkx3. 1 and Msmb promoters have recently been demonstrated to be targets of the histone methyl transferase EZH2 that represses gene expression through H3K27 trimethylation. qPCR and western blot analyses showed that Ezh2 was specifically overexpressed in LXR knockout prostates when animals were fed a high cholesterol diet (Figure  5A, 5B ). Immunohistochemistry further confirmed overaccumulation of EZH2 in proliferative PCNA+ cells in LXR knockout prostates, when animals fed a high cholesterol condition (Figure  5C ). This  suggested that the effect of cholesterol on the development of PIN was dependent on down-regulation of Nkx3.
Given the role of Msmb repression as a maker of prostate cancer progression and a bona fide tumor suppressor gene  [35] [36] [37] , we speculate that Msmb overexpression in WT mice prostates represents a defensive molecular mechanism against the metabolic stress induced by a high cholesterol diet. Among canonical LXR functions, primum movens leading to PIN phenotype in prostate of Lxr-null mice could originate from deregulation of inflammatory response in prostate tissue as suggested by gene ontology (Dataset S3). Indeed, inflammation has been widely associated with prostate cancer development. Even though there was no clear CD45+ staining Lxr-/in dorsal prostate in high cholesterol condition (Figure  S7A ), Cd45 expression measured by qPCR was 2-fold increased compared to WT (Figure  S7B ).
Human dataset analysis pointed out that LXRb but not LXRa expression could be linked to EZH2 expression while both isoforms need to be invalidated to induce a PIN occurrence in mice (Figure  S8 ). Absence of any change in LXRa expression could explain the lack of a clear deregulation of some LXR target genes in Oncomine datasets (data not shown). Moreover, both LXRa and LXRb have been demonstrated to be expressed and functional in human PCa cells  [8, 38]. These observations suggest that EZH2 deregulation could be linked to a mechanism specifically depending on LXRb. Such specificity has already been shown in human, particularly in a study on preeclampsia providing a LXRb-dependent risk in this pathology  [39]. Another point emphasized by the human dataset is the absence of NKX3. 1 expression changes between normal prostate, carcinoma and metastasis group in both examined cohorts (Figure  S8 ).
NKX3. 1 expression profiles are somehow unexpected, as this gene has been largely reported as a tumor suppressor gene in the prostate. Nevertheless, various mechanisms have been demonstrated to repress NKX3. 1 during carcinogenesis and these observations suggest that filtrating analysis of human datasets based on association with identified oncogenic alterations, such as PTEN inactivation  [40] , should me more informative. Altogether, our results show that LXR act as ''gate keeper'' in mouse prostate to prevent cholesterol accumulation and subsequent PIN development. Our findings further suggest that the metabolic status of the prostate can govern epigenetic processes involved in prostate cancer progression.
Cell nuclei were stained using Hoechst 33342 (Sigma-Aldrich) at 1 mg/ml. Apoptotic nuclei were visualized through a TUNEL reaction relying on terminal deoxynucleotidyl transferase (TdT; Euromedex, Souffelwegersheim, France) and biotin-11-dUTP (Euromedex), dATP (Promega, Charbonniere, France). Positive nuclei were revealed by addition of extravidin-coupled alkaline phosphatase and FastRed TR/Naphthol AS-MX substrate (Sigma-Aldrich). Nuclei were counterstained with Mayer hematoxylin solution. Cross-sectional areas of the prostate were photographed using a Zeiss Axioplan fluorescence microscope and the Axiovision 4. 2 software (Carl Zeiss Vision GmbH, Le Pecq, France). Lipid stainings were performed on cryosections with Oil-Red-O (Sigma-Aldrich) as previously described  [44].
Transcriptomic and Pathway Analyses Microarray study is detailed in Text S1. Briefly, mRNA samples were analyzed using Agilent 44K Whole Mouse Genome microarrays (Agilent Technologies, Palo Alto, CA). For each microarray, log ratio, fold-change and p-value were determined using the Rosetta Resolver Gene Expression Analysis System and these criteria were used for Venn analysis by threshold method. Microarrays results were deposited in the EBI MIAME-compliant database (E-MTAB-546).
Acknowledgments We are grateful to  Dr. David Rouquie ( Bayer CropScience, Sophia Antipolis, France ) for his help with microarray analysis and gene clustering. We thank  C. Damon-Soubeyrand ,  A. De Haze , and  J. P. Saru  for technical assistance with molecular biology;  C. Puchol  and  S. Plantade  for animal facilities. We warmly thank  Dr. Aline Probst  for her careful proofreading of the manuscript. Pathology analysis was performed on the @nipath Clermont facility.
This study was supported by research grants from  Association de Recherche sur les Tumeurs Prostatiques, Ligue contre le Cancer (Allier committee) ,  Fondation pour la Recherche Medicale (FRM) ,  Fondation BNP-Paribas ,  Association pour la Recherche contre le Cancer (ARC) , and  Canceropole Lyon Rhone-alpes Auvergne (CLARA). AJCP and JD were funded by MNERT grants and EV by a grant from  FEDER -Region Auvergne  and  ARC. GA was funded by  Region Auvergne program. HDB was funded by  Region Auvergne ''Nouveau Chercheur'' program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Spectra were calibrated using an external standard composed of bradykinin fragment 1-7 (M ϩ H ϩ ϭ 757. 399), angiotensin II (human) (M ϩ H ϩ ϭ 1046. 542), P14R (synthetic peptide) (M ϩ H ϩ ϭ 1533. 858), ACTH fragment 18 -39 (human) (M ϩ H ϩ ϭ 2465. 198), and insulin oxidized B chain (bovine) (M ϩ H ϩ ϭ 3494. 651) (MSCAL2, Sigma Aldrich). With MALDI-TOF/TOF, the mass tolerance for precursor ions is specified by a range based on the resolution of the precursor mass. Here, the relative mass window was fixed at a value of 200. The MS/MS data were searched with a mass tolerance of 500 ppm. Data Evaluation and Statistical Analysis-For two-dimensional DIGE analysis, scanned gels were analyzed with Progenesis Same-Spot software, version 4. 1 (NonLinear Dynamics, Durham, NC). The differential in-gel analysis module was used to compare quantitatively the normalized volume ratio of each individual protein spot-feature from a Cy3-or Cy5-labeled sample on a given gel relative to the Cy2-signal from the pooled sample standard corresponding to the same spot feature.
Within each gel, the co-resolved fluorescent signals from each protein were co-detected by the software, and abundance measurements were made directly of the internal standard without interference from gel-to-gel variation. One-way analysis of variance (ANOVA) was performed with SameSpot software and was used to calculate significant differences in the relative abundances of proteins from control and irradiated mice and in glycosylated and deglycosylated sera. Principal component analysis (PCA) of twodimensional DIGE quantitative data was performed using the statistical module of the Progenesis SameSpot software and was used in interpreting relationships between experimental groups. For MALDI-TOF analysis, the MS profiles of permethylated Nglycans were further processed using Data Explorer, version 4.