dataesr/scientific-paragraphs-categorization huggingface dataset:
Study design This single-center (Clémentville Clinic, Montpellier, France), retrospective study includes all patients operated on between April 2016 and January 2021 (including the first 42 patients operated on between April 2016 and April 2018 already studied in September 2018  [20] ). They represent the all-consecutive patients consulting for hemorrhoidal pathology, eligible for surgery and having opted for RFT among other proposals (Milligan-Morgan, DGHAL, or hemorrhoidopexy). These patients had either hemorrhoidal prolapse and/or bleeding that resisted the usual hygienic-dietary rules, topical treatments, and rubber band ligations. Exclusion criteria were predominant external hemorrhoidal thromboses or anal fissures. Pre-and intraoperative data were systematically recorded, including evaluation of hemorrhoidal prolapse following the Goligher scale (1-4)  [21] , bleeding intensity, number of hemorrhoids treated, energy delivered, and intraoperative complications.
Then, all patients were followed up for 4 to 8 weeks postoperatively as outpatients (which allowed to collect data about work stoppage, complications, bleeding, and prolapse) and, in May 2021, received information by mail before a telephone interview conducted between May and September 2021, by a gastroenterology resident who did not know the patients to limit interview biases. This data collection recovered preoperative and postoperative information on hemorrhoidal prolapse always following the Goligher scale. Bleeding and overall anal discomfort were noted by the patients according to a verbal analog scale using a validated "proctological symptom scale" ranging from 0 (absence) to 10 (very important)  [22]. They also rated the effectiveness of the treatment and their satisfaction on another verbal analog scale (from -5, deterioration to +5, improvement).
Statistics Frequencies and percentages for categorical variables and means and standard deviations for continuous variables describe the study sample after assessing the normality of the data using the Shapiro-Wilk test. Analysis of changes before and after RFT was performed using Student t-test for paired series. Comparisons between groups were made using the Student t-test (or Mann-Whitney test where appropriate) for continuous criteria and using the chi-square test (or Fisher exact test if applicable) for categorical criteria. Relationships between continuous variables were studied using Pearson r correlation coefficient (or Spearman where appropriate). Analysis of a learning effect was performed by distinguishing 4 time-ordered periods of equivalent size. Recurrence was analyzed using survival methods, taking the date of intervention as the starting point, considering time to recurrence or time to the last report.
e. an overall reintervention rate of 5. 6%. This reintervention took place on average 31 ± 11. 13 months (range, 15-43 months) after the first. As hemorrhoidal RFT is a recent operative technique, with little experience, the patients were separated into 4 equal subgroups according to the date of intervention in order to investigate the existence of a possible learning curve. In order to avoid any chronological bias, the first group operated having a greater probability of recurrence compared to the more recently operated group and taking into account the time to relapse, the data were analyzed according to a Kaplan-Meier survival curve. No significant difference was found between each patient quartile for time to recurrence (Fig. 3 ), bleeding or prolapse.
6 isfactory level of participation for a 5-year retrospective study, at 86. 3%. The descriptive data of the study population are similar to other studies on the subject with a sex ratio of approximately 2/3 male and an average age of the 5th decade suggesting the absence of inclusion bias. The follow-up of more than 62 months for the first patients and an average follow-up of more than 30 months are very significantly the longest published to date with this technique in France. The results are consistent with those of the prospective studies performed  [30, 31] , including the use of analgesics  [30, 31, 36]. Finally, reproducible and validated clinical symptom assessment tools were used, including a validated "proctological symptom scale"  [22]  and the HEMO-FISS-QoL score  [23]. The primary endpoint, QoL estimated from this HEMO-FISS-QoL score, correlated well with the reported hemorrhoidal discomfort, attesting to the proper use of this questionnaire and its correct reflection of the QoL experienced by the patient and confirming the effectiveness of the telephone interview, which could have been questioned.
4% of the patients requiring at most only stage I painkillers vs. 51. 3%) [20]. Acceptability was even better with time since the wish to be reoperated if necessary by the same technique went from 84. 6% to 91. 6% and the rate of recommendation from 89. 7% to 96. 3%. Data analysis demonstrates the feasibility of outpatient RFT and its effectiveness on improving bleeding, hemorrhoidal prolapse, and QoL. Bleeding and prolapse disappeared completely in only 52. 0% and 30. 0% of patients, respectively. Moreover, for patients who still have bleeding, it becomes minor. In view of these results, one may wonder whether the preferred indication for RFT would not be the treatment of hemorrhage rather than that of prolapse but the results obtained do not allow this to be the case. Indeed, there is no more recurrence with grade 4 prolapse and the mean reduction of the hemorrhoidal prolapse from grade 3 to grade 2 leads to a significant improvement in QoL without the need for manual reintroduction.
How fast do miRNAs evolve? While we found conservation of some miRNAs between unicellular members of Acanthamoebae, and also between the group 4 dictyostelids D. discoideum and D. firmibasis, the other identified miRNAs were all unique for each species. This indicates a rapid evolution of Amoebozoan miRNAs. To analyze in more detail how some of these miRNAs evolved, we investigated the two most closely related organisms in our dataset, D. discoideum and D. firmibasis. While some of the miRNAs seem to have been acquired or lost gradually, for others we could identify insertions or deletions of whole miRNA modules (Fig. 4 ). The fact that these two closely related organisms have such a diversified miRNA repertoire shows that broadly, their individual miRNAs are under weak evolutionary pressure, consistent with the minor phenotypic effects we observed upon depletion of miRNAs in D.
Acanthamoebae were first grown axenically in PYG w/ additives (ATTC medium 712 at 30 °C) and subsequently grown and harvested similar to the social amoebae, on SM Agar/5 plates with charcoal, with E. coli 281 as food source. Physarum polycephalum was grown on oats on 2% agar. Parts of sclerotium were scraped from the plate and resuspended directly into TRIzol Reagent. For the growth curves of D. discoideum wildtype (AX2) and drnB -strains, cells were grown axenically in HL5-c (Formedium) with 100µg/ml Pen Strep (Gibco) at 22 °C, shaking at 180 rpm, and quantified in a hemocytometer. For strain numbers and access to strains see attributes file at SRA under BioProject accession number PRJNA972620.
miRNA identification Quality control of raw sequencing reads was performed with miRTrace  54  , after which they were processed by trimming the sequencing adapters and selecting reads of size 18-35 nt with Cutadapt  55. Small RNAs were mapped to the reference genome or E. coli genome, with a maximum of one mismatch, and multimapping reads placed according to the fractional weighted probability, using Shortstack v3. 8. 5  56. Clusters with potential miRNA candidates were selected and further analyzed with an in-house python script available on https://github. com/Bart-Edelbroek/amoeba_miRNAevo. Briefly, in the first round, exploratory analysis was done by mapping reads with no mismatches to each selected cluster and folding the cluster using the ViennaRNA RNAlib-2. 6. 2 python package  57. If the cluster could be folded into a hairpin-structure, the positions of the mir-5p and mir-3p were defined based on the mapped reads.
Analysis of miRNAs Analysis of the identified miRNAs was performed in R. Non-coding RNA regions were identified and annotated in the genome using Infernal Library preparation was performed with 1. 5 µg of filtered genomic DNA using the SQK-LSK112 nanopore sequencing kit. 100 ng of final prepared library was loaded on a MinION Mk1C with R10. 4 flowcell and sequencing was performed for 72 hours. Basecalling, adapter trimming and read-splitting was performed with Guppy v6. 3. 2. The data was filtered using Filtlong v0. 2. 1 to retain the best 5 Gbp of data and remove reads smaller than 1000 bp. Assembly was done using Flye v2. 9. 1 in nano-hq mode  58  , and two rounds of long-read polishing were done using Medaka v1. 7. 2. The filtered reads used for assembly can be accessed from NCBI BioProject PRJNA972620.
Acknowledgements We would like to thank  Jon Jerlström-Hultqvist  for help with D. firmibasis sequencing and genome assembly;  Gernot Glöckner  (deceased) and  Pauline Schaap  for help with initiating this study;  Wolfgang Marwan  and  Lionel Guy  for providing P. polycephalum and Acanthamoeba strains, respectively. We are also grateful to  Andrea Hinas ,  Pauline Schaap  and  Gerhart Wagner  for critical reading and commenting on the manuscript. Sequencing was performed by the  SNP&SEQ Technology Platform in Uppsala. The facility is part of the  National Genomics Infrastructure (NGI) Sweden and Science for Life Laboratory. The SNP&SEQ Platform is also supported by the  Swedish Research Council  and the  Knut and Alice Wallenberg Foundation. Computations and data storage were enabled by resources provided by the  National Academic Infrastructure for Supercomputing in Sweden (NAISS)  at UPPMAX, funded by the  Swedish Research Council  through grant agreement no.
Data availability All sequencing data generated in this study can be accessed at NCBI BioProject PRJNA972620. sRNA sequencing data of different Amoebozoan species for miRNA discovery are available with BioSample accessions SAMN35084086 -SAMN35084094. sRNA sequencing data to compare the D. discoideum drnB -knockout strain with wildtype are available with BioSample accessions SAMN35084095 -SAMN35084098. Third-generation sequencing data of D. firmibasis, used to assemble the genome, is available with BioSample accession SAMN35084099. The D. firmibasis genome assembly used in this study is deposited at https://doi. org/10. 5281/zenodo. 7937210. Data used for analysis of miRNAs, synteny between D, firmibasis and D. discoideum, and differential miRNA expression is available at https://github. com/Bart-Edelbroek/amoeba_miRNAevo/tree/main/data_in.
Code availability For initial curation of the miRNA candidates, we used a python script available at https://github. com/Bart-Edelbroek/amoeba_miRNAevo. A folder with scripts and sample data Extended Data Fig. 4  | Length distribution of sRNAs mapping to miRNA-loci. Histogram of read lengths mapping to loci of miRNA-hairpins. For D. firmibasis, mapping was done to the de-novo sequenced genome.
b Circos plot of the D. firmibasis (pink) and D. discoideum (purple) main contigs, with links showing syntenic regions containing a miRNA in either D. firmibasis or D. discoideum. (Note that ddi-mir-1177 is the only miRNA identified to be conserved between the two dictyostelids). The name of the miRNAs present in the syntenic regions are shown on the outside of the plot. c Intergenic region containing ddi-mir-1179 in D. discoideum, and below the aligned syntenic region in D. firmibasis. The DNA sequence in the dashed box was further aligned and the hypothetical ncRNA folded in silico, which yielded the displayed hairpin-like structure. The positions of ddi-mir-1179-5p and ddi-mir-1179-3p are indicated in red and cyan, respectively, in both the DNA alignment and RNA secondary structure. 46 Number of sRNAs mapping to spliceosomal RNAs and other ncRNAs were omitted since they were very low, but they can be accessed through GitHub.
-15  to identify regions of interest containing Argonaute or Dicer homologs. Conserved domains in the homolog candidates were identified using PfamScan. Sequences were aligned with MAFFT v7. 520 62 , trimmed with trimAl v1. 4. rev15, and phylogenetic consensus trees were constructed using IQ-TREE v2. 2. 2. 3 with the to perform an example run is provided in the repository. Downstream analysis of the miRNAs, Blosum62 amino-acid exchange rate matrix 63. genome synteny analysis, and differential miRNA expression analysis was performed in R and the code is provided at https://github. com/Bart-Edelbroek/amoeba_miRNAevo. Further provided in the repository are the plots generated in the analysis, and helper scripts used for generating input data.
The low intensity isometric exercise consisted of 24 intermittent isometric tetanic contractions (stimulation frequency: 100 Hz; train duration: 200 ms, 3 mApulses of 50 μs duration, one train every 5 s). GM and SOL muscles were extracted and animals were killed by intra-cardiac injection of Eutha-sol®, while still fully anesthetized. Force data during muscle stimulation were sampled at a frequency of 1000 Hz and collected using a custom written software based on Matlab (v 7. 5. 0, The Mathworks Inc. , MA, USA). Maximal force (Fmax), time to maximal force production (tFmax), maximal rate of force development (RFD), time to maximal rate of force increase (tVmax) and passive force at optimum muscle length (Fpassive) during the first and last two contractions of the high-intensity protocol were subsequently determined running a 50 Hz filter and averaged for the two respective consecutive contractions.
The tip of the micropipette was inserted into to insulated part of the fiber and the pipettes connected to an RK-400 patch-clamp amplifier (Bio-Logic) in whole-cell voltage-clamp configuration. Command voltage pulse generation was achieved with an analogue-to-digital converter (Digidata 1440A; Axon Instruments) controlled by pClamp 9 software (Axon Instruments). Fibers were bathed in the TEA-containing extracellular solution  [36]. Muscle fiber contraction was prevented by the presence of a large concentration of EGTA in the intracellular-like solution. For intracellular calcium measurements, the micropipette was filled with the intracellular-like solution also containing 0. 2 mM of the calciumsensitive fluorescent indicator Fluo-4 FF. A protocol consisting of trains of thirty, 5 ms-long depolarizing pulses from -80 mV to +60 mV, delivered at 100 Hz, was applied and then repeated 2, 5 and 10 min following the first series.
Microscopic fields were recorded at a 10-fold magnification (Axioskop 2, Carl Zeiss Ltd. , Welwyn Garden City, UK) in an overlapping fashion to cover the entire cross-section and assembled digitally with AxioVision software (Carl Zeiss Ltd). The efficiency of overexpression was estimated in one cryosection of the mid-belly portion of each α/β CaMKII-transfected muscle, which was stained for CaMKII using colorimetric staining. Subsequently individual microscopic fields were assessed for the number of fibers with prominent staining for CaMKII and the total fiber number. On average 234 and 386 fibers were counted for SOL and GM muscle, respectively. In order to illustrate plasmid-transfection mediated overexpression of α/βCaMKII, cryo-sections were sequentially reacted with the pan-CaMKII antibody (BD Bioscience #611292, dilution: 1:200) and then Alexa 488/555 secondary antibody (Invitrogen) and CaMKII was visualized with on a TCS SP5 confocal microscope (Leica, Milton Keynes, UK) with settings as described  [21].
Statistics Data were curated using MS-Excel (Miscosoft, Kildare, Ireland) and analyzed in SPSS (version 23, IBM Corporation, Armonk, NY, USA). Effects on a given parameter, or the derived ratios and fractional differences characterizing the exercise and plasmid effects, respectively, were assessed with repeated-measures, or univariate ANOVAs, based on an assumed sphericity and post hoc tests of least significant difference and/or the sign test. Mauchly tests were conducted to assess the possibility of a violation of the assumed sphericity. For the parameters gathered from intact muscle in situ, this comprised where applicable the repeated factors 'plasmid' (pcDNA3-αCaMKII & pcDNA3-βCaMKII, control), muscle (SOL, GM), exercise (first two contractions, last two contractions). For the parameters gathered from single fibers this comprised where applicable the repeated factors 'plasmid' (pcDNA3-αCaMKII & pcDNA3-βCaMKII, control), excitation number (1, 2, …, 10), excitation train (0, 2, 5, 10 min).
Acknowledgements We thank  Dr. Wouter Eilers  for excellent technical assistance and  Prof. em. Arnold de Haan  for excellent guidance during the project. We thank  Prof. MN Waxham  ( University of Texas, Houston, USA ) and  Prof. Frank W. Booth  ( University of Missouri, Columbia, USA ) for the supply of CaMKII expression plasmids and the luciferase reporter plasmid.
Acknowledgments This work was supported by the  "Rising Star" (Pays de la Loire Region)  and " DBM" (CNRS-INSB)  grants, awarded to  François Delavat. Pauline Crétin  was supported by the  CNRS-MITI (GdR OMER). Authors would like to thank  Jordan Vacheron  ( DMF, University of Lausanne ) and  Eric Giraud  ( IRD Montpellier ) for sharing the pOT1e and pMG103-nptII-mcherry plasmids, respectively.
When using genotype data, the genotype covariance matrix was built directly from the unphased VCF file using the R package, SNPRelate  [36]. When using haplotype data, PCA was applied to matrices built with ChromoPainter  [23]  that indicate similarity between samples through lengths of IBS tracts. The first and second PCs were plotted (Figure  5 ) and we measured how well the modern and ancient populations clustered by computing the silhouette coefficient. This metric evaluates clusterings using information inherent to the dataset, so that clustering can be compared across different simulated datasets  [37]. Measuring cluster distinction is important, since distance metrics in component space can be thought of as proxies for population split times  [38].
Materials and methods Between January 15th 2020 and February 3rd 2020, a prospective cross-sectional web-based survey, named ENDOVIE, was conducted among women diagnosed with endometriosis, in order to investigate their medical journey. The study population was targeted from the Ipsos Panel, which gathers data from 235,171 subjects who are highly representative of the French population, and from EndoFrance, a nonprofit patients' organization for endometriosis. The survey was conducted without quotas, with the objective of interviewing a significant number and a large panel of women with endometriosis, irrespectively of their age, educational and socio-economic level, and appurtenance or not to a patients' association  [8]. Individuals in the target sample pool received an email invitation to participate, with a link to a secure anonymous survey website.
Pain was assessed through the visual analogue scale (VAS), which scores vary from 0 (no pain) to 10 (pain as bad as it could possibly be). Statistical analyses and tests were performed using Cosi software (M. L. I. , France, 1994). Descriptive statistics include frequency tables, means, standard deviations and 95 % confidence intervals (95 % CI). A p value <0. 05 was considered statistically significant. As a member of the French and European professional Market Research and Opinion bodies, Ipsos France is committed to applying the ICC/ESOMAR code for opinion and market research. This code of conduct defines the ethical rules for Market Research professionals and sets out the protection offered to participants (see https://www. ipsos. com/en/privacy-data-protection). Ipsos France has received ISO 20,252: 2012 certification by AFNOR CERTIFICATION.
Molecular modelling of variants of AmSP-WT Glucosyl-enzyme intermediate 3D-models were built for AmSP-Q353F and AmSP-P140D using the following procedure and the Rosetta software  [22]. Glucosylated-aspartyl 192 residue from chain A of crystal structure of BaSP-WT (PDB: 2GDV-A) was inserted into the crystal structure AmSP-WT.
5 (PDB: 7ZNP) that served as initial template for both variants. As this glucosylated aspartyl is a nonstandard residue, it was absent from the database of the Rosetta software. Using Pymol3, the initial coordinates of this modified residue were retrieved. While this residue (D192) and the glucose moiety (BGC) are covalently linked in the crystal structure, the Pymol software considered them as two distinct residues. Thus, they were merged them into a single non-standard residue, which was called with a new ID, DGC. Associated charges and rotamers were calculated for this new residue using the Rosetta software. All those data were merged a single file that we added into the Rosetta database (Section 2. 7). With the DGC residue ready to be used, glucosyl-intermediates were built for the two variants of AmSP-WT.
From the crystal structure (PDB: 7ZNP), using Rosetta the native aspartyl residue in position 203 was mutated by the glucosylated-aspartyl DGC residue together with either the P140D or Q353F mutation. For each variant (AmSP-Q353F or AmSP-P140D), a sample of 50 conformers was generated thanks to the program Backrub from Rosetta suite, with 10 000 tries. In parallel, 12 conformers of (+)-catechin were also generated using the Mercury software (CCDC)  [23]  from the crystal structure OZIDOR of (+)-catechin.
Highly conserved structural features and potential activity of AmSP-WT Through structural comparison of BaSP-WT (PDB: 1R7A, 2GDV), BaSP-Q345F (PDB: 5C8B), and our recently determined structure of AmSP-WT (PDB: 7ZNP), we identified the conserved residues likely involved in the reaction mechanism and potential substrate interactions (Table  S1 ). The -1 subsite of SPs, also called donor site, has an optimal topology for binding glucose and is conserved between BaSP-WT and AmSP-WT (Figure  1 ). The configuration of the two catalytic residues involved in the reaction mechanism are also almost identical (Figure  1A , in blue): a glutamyl residue acts as a general acid/base catalyst (E243 for AmSP-WT and E232 for BaSP-WT) and an aspartyl residue performs the nucleophilic attack (D203 for AmSP-WT and D192 for BaSP-WT).
When we compare the apoenzyme of BaSP-WT (PDB: 1R7A) with our newly obtained apoenzyme of AmSP-WT (PDB: 7ZNP), a striking difference in the positioning of loop A is noticed. The enzyme has already an opened conformation and is in the "acceptor binding mode" with Y352 residue pointing inside the active site (Figure  1 , in magenta) and R141 pointing outside (Figure  1 , in orange). This open conformation was also observed for BaSP-WT crystallized with the end-product of the reaction after hydrolysis of glucose (PDB: 2GDV, chain B). Moreover, crucial conserved residues involved in binding of both phosphate and fructose, Y196 and H234 for BaSP-WT vs. Y207 and H245 for AmSP-WT, are in the same conformational positions thus allowing sucrose phosphorylase activity (Figure  1B , in cyan)  [21]. In BaSP-WT, Y132 is located at the entrance of the active site and contributes to sucrose specificity thanks to hydrophobic interactions with Y196 and F206.
Acknowledgements We would like to thank our patient partners and all the health professionals who have contributed to the adaptation of the intervention, and facilitated the set-up of this trial. We would also like to thank  Mrs. Abdullah  and  Mrs. Bourgouin  at the  INSERM and University of Toulouse III Paul Sabatier  for their unwavering support as we started setting up this randomized controlled trial. And thanks to  Bettina Couderc  for her advice and support on legal submissions.