dataesr/scientific-paragraphs-categorization huggingface dataset:
Gene expression levels in the presence of DHT-activated AR-WT, AR-Q641X_EtOH, or AR-V7_EtOH (Datasets A) were compared with the reference dataset B corresponding to Control_EtOH. The number of differentially expressed genes with adjusted p-value < 0. 05 and |log 2 FC| > 1 is indicated. The number of under-and overexpressed genes, A < B and A > B, respectively, is also indicated. TMPRSS2 and KLK3 were positively regulated in all conditions, and the drop in the expression level of ITGA3, HDAC9, COL16A1, SMARCD3, and ITGB4 observed with DHT-activated AR-WT was significantly attenuated in cells expressing constitutively active AR variants (Fig. 3 ; Fig. S3 ). We next checked by realizing a time-course proteomic analysis in LNCaP cells whether the repressive transcriptional activity of DHT-activated AR-WT was noticeable at the protein level.
Similar AR-binding sites associated with both up-and downtranscriptional regulation by DHT-activated wild-type AR A possible molecular mechanism to explain differences in transcriptional repressive activities between AR-WT and constitutively active AR variants could be distinctive recognition of so-called negative AREs (nAREs)  [48]. However, to go deeper in this hypothesis, we first wondered whether there was a difference in ARbinding sites associated with transcriptional activation and repression by DHT-activated AR. So, available AR ChIP-seq data from LNCaP and VCaP cells were downloaded from GEO database and intersected with the lists of up-and downregulated genes. Sequences corresponding to AR-binding sites (500 bp centered on the peak summit) were subsequently retrieved from human reference genome (hg19/GRCh37) and submitted to MEME-ChIP webserver (https://meme-suite.
AR variants disengaged from corepressor recruitment As AR ligand-binding domain and AF-2 are known to present interfaces for recruitment of numerous coregulators, the lack of the C-terminal part in constitutively active AR variants could lead to the formation of particular complexes, explaining therefore the decrease in their transcriptional repression capacities. To analyze regulatory complexes formed around AR-WT and constitutively active AR variants, the BioID2 approach was applied (Fig. S7 ). A mass spectrometry analysis was thereafter carried out from purified biotinylated proteins from myc-BioID2, myc-BioID2-AR-WT, myc-BioID2-AR-Q641X, and myc-BioID2-AR-V7 transduced LNCaP cells. After raw data normalization, 78 biotinylated proteins were underrepresented in the presence of myc-BioID2-AR-Q641X and myc-BioID2-AR-V7 compared with myc-BioID2-AR-WT.
An enrichment analysis indicated that these 78 potential AR partners fit mainly in GO molecular function terms around transcriptional regulation, including 'nucleic acid binding', 'transcription coregulator activity', 'heterocyclic compound binding', 'organic cyclic compound binding', 'transcription corepressor activity', and A B Fig. 4. BioID analysis of AR interactome. (A) Gene ontology (GO) analysis of 78 potential partners identified by mass spectrometry using the BioID2 approach and underrepresented in AR variants conditions compared with AR-WT. (B) Among the 13 proteins related to the 'transcription corepressor activity' GO term, 7 are known as experimentally proved AR partners (BIOGRID database). 'transcription regulator activity' (Fig. 4A ). According to the BIOGRID database, among the 13 proteins related to 'transcription corepressor activity', 7 are known as experimentally proved AR partners, including BCOR, NCOR1, NCOR2, and PIAS1 (Fig.
5 ; Table  S3 ). These results lead us to postulate that following DHT activation, AR-WT could ultimately trigger to the repression of a panel of genes and that some of these genes would be involved in cell plasticity. To strengthen our hypothesis, we further investigated the profile of transcription repression by fulllength AR in available RNA-seq datasets from prostate cancer cells. We choose GSE125014 and GSE148397 datasets originating from LNCaP cells expressing the T878A mutant AR and from VCaP cells expressing a wild-type AR, respectively. LNCaP cells were stimulated with 10 nM DHT for 4 and 24 h, and VCaP cells were stimulated with 1 nM R1881 for 8 or 22 h. In order to compare our dataset to those of GSE125014 and GSE148397, all data files have been processed with DESeq2 for normalization and identification of differentially expressed genes.
A B From these three RNA-seq datasets, a total number of 1718 repressed genes were identified (adjusted Pvalue < 0. 05 and log 2 FC < -1 for GSE158557 and GSE125014 data; adjusted P-value < 0. 01 and log 2 FC < -2 for GSE148397 data) with partial overlapping (Fig. 7A ). Hallmark gene sets associated with these 1718 repressed genes using the Molecular Signatures Database (MSigDB) and Enrichr software revealed the following hallmarks, 'epithelial-mesenchymal transition', 'UV response Down', and 'KRAS signaling Up' as significant MSigDB terms (Fig. 7B ). Gene ontology enrichment analysis further revealed 'cell adhesion', 'biological adhesion, extracellular matrix organization' as significant biological processes, 'calcium ion binding', 'integrin binding', 'collagen binding' as significant molecular functions, and finally, 'extracellular matrix', 'collagen-containing extracellular matrix', and 'presynaptic membrane' as significant cellular components (Fig.
It has been tempting to take advantage of our list of repressed genes in the presence of DHT-activated AR-WT to question publicly available AR ChIP-seq datasets for putative negative ARE. Indeed, the analysis of 500 bp genomic sequences around peak summits from GEO datasets GSE121021 and GSE148358  [31, 55]  with MEME-CHIP program  [56]  revealed AR and FOXA1 motifs as the two most represented motifs among AR-binding sites for both the panel of down-and upregulated genes. This suggests that, as far as we can conclude from available AR cistrome datasets, gene repression by a full-length AR does not rely on binding to peculiar AREs. Besides, it has been reported that constitutively active AR variants display their own cistrome  [57] [58] [59]. Consequently, it remains to determine whether particular pioneer factor recruitment and distinctive chromatin conformation around downregulated genes could explain the duality between full-length AR and constitutively active AR for gene repression.
Proteins with adjusted P-value < 0. 05 and |log 2 FC| > 0. 6 are shown in red (significantly under-represented proteins) and blue (significantly over-represented proteins). Number of differentially represented proteins are indicated below the plots. The 14 down-represented proteins at 24 and 48 h after DHT treatment are shown in green. Fig. S5. Pipeline for RNA-seq/ChIP-seq intersection and motif analysis. AR ChIP-seq data available in nar-rowPeak file format were downloaded from the Gene Expression Omnibus (GEO) database. GSM3424005  [55]  referring to AR ChIP-seq from LNCaP cells cultured in complete medium provides 21127 AR binding sites (peaks). Samples GSM4462682, GSM4462683 and GSM4462684  [31]  corresponding to three replicates of VCaP cells treated with 1nM of R1881 for 22h were first subjected to the bedtools intersect function from pybedtools library on python 3 to identify 30941 AR peaks common to the three replicates.
Acknowledgements The RNA-seq was performed by the  GenomEast platform (IGBMC, Illkirch). Special thanks to  Mathieu Jung  for the first round of bioinformatical analyses and to  Aline Humbert ,  Rachel Maillot , and  Nathalie Messa  for their remarkable contribution. This work was funding by  ARTP (Association pour la Recherche sur les Tumeurs Prostatiques) ,  Association Alsace contre le Cancer , and  La Ligue contre le Cancer  (Grant from the  CCIR-GEA).
Data accessibility All RNA-seq data are available at NCBI Gene Expression Omnibus (GEO) under GSE158557 (https://www. ncbi. nlm. nih. gov/geo/). Proteomic data are available at the ProteomeXchange Consortium via the PRIDE database under PXD029454 for BioID2 analysis and PXD029520 for kinetic analysis (http://www. ebi. ac. uk/ pride).
Inhibition of IL-17 To date, very few trials have been conducted in vasculitis. A trial is on hold with secukinumab in patients naïve to biologics and with newly diagnosed or relapsing GCA  (162). Some results suggest that secukinumab could be efficient in BD as promising results come from patients with non-infectious uveitis  (163). Trials to modify the Th17/Treg balance have been performed with low dose IL-2 administration and even more are on-going (NCT01988506, NCT04065672, NCT04387942) (161).
Sirukumab efficacy, an IL-6 production inhibitor, is currently testing in GCA  (167). Tocilizumab can be considered in relapsing or refractory TAK when conventional disease modifying anti-rheumatic drugs (DMARDs) or TNF blockers are not sufficient to control disease activity  (14, (168) (169) (170). Apart from LVV, Tocilizumab was also tested in BD with promising results and clinical trials are on-going (NCT03554161)  (171, 172). In AAV, some case reports have been published but larger clinical trial are required  (173).
Inhibition of IL-1ß IL-1ß is required for Th17 differentiation and enhances Th17 cell differentiation, as shown in BD  (174). Different tools are available to block this pathway, either with IL-1 receptor antagonist (anakinra) or by targeting directly the cytokine itself (canakinumab, gevokizumab)  (175). Clinical trials are on-going to test anakinra in addition to corticosteroids in GCA (NCT02902731). Anakinra is currently testing in KD (NCT02179853, NCT02390596). In BD, canakinumab (NCT02756650), anakinra and gevokizumab were tested and results suggest a mixed effect depending on clinical manifestations  (176) (177) (178) (179) (180) (181). Canakinumab was also tried in HUV and results are expected (NCT01170936).
Inhibition of IL-23 As mentioned above, IL-23 is required for Th17 differentiation  (15). Different biologics were developed to target this cytokine with the example of ustekinumab, that targets p40 subunit and thus potentially inhibits both Th1 and Th17 pathways  (182). Precisely, ustekinumab was tested in a GCA patient and inhibited Th1 and Th17 polarization  (183). A recent trial showed disappointing results but they must be analyzed carefully for several reasons (uncontrolled trial, time of analysis)  (184, 185). Other trials displayed promising results and this treatment is currently testing in relapse or refractory GCA (NCT03711448)  (186). Among LVV, ustekinumab was also tested in three TAK patients with promising results  (187) (188) (189). Recently, guselkumab, that specifically binds to the p19 subunit of IL-23, is currently tested in GCA (NCT04633447).
Similarly, baricitinib, which inhibits JAK1/JAK2, has been tested in GCA. Fifteen relapsing GCA patients were enrolled in an open-label pilot study and preliminary results demonstrated evidence of both efficacy and safety. Discontinuation of glucocorticoids was allowed in the majority of patients with relapsing GCA but larger trials are needed to confirm these results  (196). Finally, the inhibition of the complement pathway with avacopan (anti-C5a receptor) in AAV showed promising results but its effects on the Th17 pathway have to be characterized  (197). Overall, more clinical data are needed to conclude on the potential benefit to specifically target IL-17 in these diseases.
Experimental plan An adaptive test was performed between May 2019 and November 2020, which means that process conditions (washing solution, storage temperature, etc. ) were gradually adapted according to the results obtained. After thawing in a water bath (set to 40°C to obtain at the end of thawing 37°C in the water bath), HPC products were washed using either Lovo 3. 0 or COBE 2991. An important piece of input data used by the Lovo to adjust its washing parameters to optimize cellular recovery is the PCV percentage. Prior to washing with Lovo, the PCV percentage calculation was performed by the device based on the pre-freezing counts: ([Total volume of cellular material: red blood cells, white blood cells and platelets] / [total source product volume]) £ 100.
In the absence of clinical and biochemical signs of hypophosphatemia, a subject was considered as non-affected with XLH. After diagnosis, all children started treatment with active vitamin D analogs (alfacalcidol) and phosphate supplements according to international recommendations  [4]. In the present study, we included children with XLH who (i) were born between 1988 and 2006; (ii) regularly visited in our hospital, and therefore, had a detailed growth chart available; and (iii) had reached their final height. The whole cohort included children with XLH who were treated with rhGH and also those who did not need rhGH treatment (serving as "control group"). Children who underwent lower limb surgery were excluded from the analysis. The study was approved by the French National Data Processing and Liberties Commission (CNIL number 1920371v0), and in accordance with the Jardé law in France, the need for written consent was waived.
Study protocol and methods The follow-up period was from disease diagnosis until the last visit. For each patient, we gathered data on parameters such as gestational age at birth, weight, length/height and body mass index (BMI) at several time points. For children treated with rhGH, we retrieved data at birth, at the time of XLH diagnosis, at the start of rhGH treatment, after 2 years of rhGH treatment, at the end of rhGH treatment and at the last visit, i. e. , at final height. For children who did not receive rhGH treatment (the "control"), we collected the same types of data at equivalent stages during follow-up, namely, at birth, at the time of XLH diagnosis, at the ages at which patients in the other group initiated rhGH, 2 years later and at which they discontinued the treatment (i. e.
Statistical analysis Statistical analysis was performed using IBM SPSS (Statistical Package for the Social Sciences) Statistics for Windows, version 25. 0 (IBM Corp. , Armonk, NY, USA). The results were expressed as mean ± SD for continuous variables and as absolute number (percentage) for categorical variables. The comparisons of continuous variables were performed using Student's t test or the Mann-Whitney U test or using one-way analysis of variance, as appropriate. All p values < 0. 05 were considered significant. Figures were plotted using.
Descriptions of respondent subjects Of the 22 subjects contacted by the investigator, 20 of them, aged 43 on average (27 to 62 years), with a sex ratio equal to 1, agreed to participate in the study. One subject refused to participate without explanation and another never answered the phone calls. All the people asked were very satisfied with the interest shown in the employment of people with BD and stated that they were concerned about this issue. A subject in the depressive phase, in therapeutic discontinuation, was excluded at the time of the interview. He was not able to answer questions constructively. The interviews lasted 45 to 90 min. Data saturation was obtained from the 16th interview. We conducted three additional interviews to confirm the results. The socio-professional characteristics (educational level: professional certificate, bachelor's degree and above, current professional situation), Recognition as a Disabled Worker and clinical characteristics (age of diagnosis, number of previous hospitalizations for current therapeutic BD, psychiatric comorbidities) of the 19 people who participated in an interview are shown in Table  1.
Introduction In the introduction, the others recall that animal models are important for conducting research in biology and particularly in the biomedical field. Today there are many animal models and for any research, the choice must be made on the best animal model suitable for research, which requires above all to know the model well. As said above, the work presented here falls within this logic and concerns two strains of mice particularly dedicated to the study of prostate cancer. First, it is important to give an anatomical description of the organ concerned, here the prostate, with a mapping of the cells in the different lobes. Today, the development of molecular biology and gene databases makes it possible to establish an extremely fine mapping of cells by highlighting the genes or their expression products at the level of the latter.
Statistical analyses Analyses used a nonimputed BIOSTAT-CHF database as described elsewhere. 11 , 23 , 24 Association with outcomes was performed using Cox proportional hazards regression analyses. Outcome prediction accuracies were assessed by calculating the area under the curve for the receiver operator characteristics curve analysis and using net reclassification index for the markers across endpoints, after adjustment for the compact and extended risk models made from previously defined BIOSTAT-CHF models. 25 Kaplan-Meier sur vival cur ves were generated to demonstrate cumulative incidences of events for tertile groupings of gut dysfunction markers with the Mantel-Cox log rank tests used to report the significance of stratification. Kaplan-Meier survival analyses were conducted using graded response of gut dysfunction markers (ie, the number of elevated metabolites above the median concentration for each particular metabolite).
BIOSTAT-CHF was supported by the European Commission ([FP7-242209-BIOSTAT-CHF; EudraCT 2010-020808-29). The present analysis was supported by the following funding to TS: the Japan Heart Foundation, National Institute for Health Research (Leicester Biomedical Research Centre), the British Heart Foundation (BHF) and the Medical Research Council (MRC) UK Consortium on MetAbolic Phenotyping (MAP/UK).
Funding BIOSTAT-CHF was supported by the European Commission ([FP7-242209-BIOSTAT-CHF; EudraCT 2010-020808-29). The present analysis was supported by the following funding to TS: the Japan Heart Foundation, National Institute for Health Research (Leicester Biomedical Research Centre), the British Heart Foundation (BHF) and the Medical Research Council (MRC) UK Consortium on MetAbolic Phenotyping (MAP/UK).
Methodology Study design and procedures We conducted a prospective, descriptive study within an open-label randomized controlled trial to assess the effect of VR on pain management for pregnant persons in labor. Prior to initiating the trial, it was approved by the Cedars-Sinai Medical Center Institutional Review Board (Pro00050082) and the protocol registered with clinicaltrials. gov (NCT03437031). Enrollment began in March 2018 and completed in February 2019. The details of the randomized controlled trial have been described in detail elsewhere  (8). In brief, subjects were included if they were nulliparous, term, having regular contractions (defined as at least every 5 min), and with a pain score on the Wong-Baker pain scale between 4 and 7. In addition, subjects were required to be ≥18 years old, Englishspeaking, and able to give consent.
Thematic and statistical analysis An inductive thematic analysis was used to examine the data collected during the interviews. The analyses were performed by an experienced researcher (C. K. ) with formal training in qualitative methods using the Dedoose software package. The transcripts were carefully read multiple times to enable total immersion in the discussions. Throughout the reading, sentences and paragraphs were highlighted and coded. Hence, key labels were inductively identified in the unstructured data. After sorting, combining, and refining the generated codes and labels, a set of inductive themes and subthemes were defined and justified with verbatim quotes. Of note, thematic saturation was achieved after completing 15 interviews. Similar instances were found in the data after the 15 th interview.
Cervical cancer screening (CCS) by Pap tests is mainly performed by gynecologists in France, but also by general practitioners (GPs) and midwives. The screening uptake is insu cient to reduce the incidence of cervical neoplasms. Our aim was to investigate the association between screening rates in patients listed with GPs and the distance between GPs' o ces and gynecology facilities. The population of GPs, and their , female patients eligible for screening over years ( -), were derived from the Health Insurance claim database. We estimated the socioeconomic level of the geographical area of GPs' o ces using the European Deprivation Index (EDI). The proximity of gynecology facilities was calculated by computing their distance from GPs' o ces (in order to adjust the proximity of gynecology facilities with EDI and performance of smears by the GP).
Variables The main outcome was the cervical cancer screening participation rate in the eligible female patient population of included GPs, measured by the refunding to female patients of cytological examination of cervical samples by the health insurance fund. Working with claim databases where patients are anonymised and not traceable for regulatory ethic reasons (we only know their gender, their age between 25 and 65 years, the designation of their GP, and the reimbursement of a pap smear), it was not possible to compute the distance between the dwelling place of patients and offices of gynecologists. However, most of the patients are registered on the patient lists of their closest settled GP and share the same environmental characteristics  (10). As a surrogate outcome of the distance between the dwelling place of patients and offices of gynecologists, we computed as our proximity indicator the density of the gynaecologists' offices around GPs' offices within 5, 10, 20, and 40 km.
Thus, the predictor was the distance between the office of a gynecologist and each GP office. This variable was computed using geo-tracking of GP offices and the gynaecologists' offices. The confounding variables on the GP level were the gender of the GP (recovered from the SIAM database) and the performance of vaginal samplings (as a binary variable) in the GP office based on telephone surveys as described in a former paper  (8). The European Deprivation Index (EDI) (  12 ) was the socioeconomic effect indicator utilized. The EDI is an ecological marker reflecting the individual deprivation experience of the general population in an area based on the census. The determination of EDI started from the construction of an individual deprivation indicator associated with both objective and subjective poverty and following the identification of the basic needs of people.
Study strengths and limitations The claim database of the CPAM of Flanders is reliable and consistent, and the data extracted from this database for a duration of 3 years are considered trustworthy. A participation rate of 98% of the targeted GPs allows us to consider that our study was based on an entire, not sampled population. Including 345 GPs, their almost 94,000 female patients eligible for CCS, and the 149 gynecologists in the area who may have been consulted by these patients, confers to this study a solid internal validity. Studies exploring the association between the density of gynecological care facilities and the CCS participation rate as the main outcome are scarce. No one has previously explored this association based on the ground distance between GPs and gynecologists. Our results match another French country-side study highlighting the same association by another method  (11)  strengthening the external validity of our finding.
There are many different compulsory health insurance regimes in France depending on the occupational sector of the insured persons. We based our study on the claim database of the CPAM of Flanders representing 80% of insured persons. This means that we missed some occupational sectors like teachers or farmers. This can possibly be considered as a selection bias though there is no reason that the 20% of missed population substantially differs from the general population as described in other contexts  (18). This does not diminish the external validity of our main result.