dataesr/scientific-paragraphs-categorization huggingface dataset:
Six metanodes contained characterized enzymes (meta-nodes C1 to C6). The other nine meta-nodes (UC1 to UC9) did not contain characterized sequences and were therefore investigated for their functions. In addition to these metanodes, the SSN also contains 20 meta-nodes with fewer than 20 sequences, and 641 singletons sharing less than 63 % identity with the sequences in meta-nodes. These small meta-nodes and singletons contain 798 sequences, which correspond to 12. 7 % of the 6308 sequences used to construct the SSN. They correspond to small sequences of less than 292 amino acids in size, which is the length of the shortest full-length GH130 sequence indexed in the CAZy database (CEP78012. 1). These short sequences appearing as singletons represent the majority (94%) of the incomplete metagenomic sequences.
The UC1, UC7 and C5 meta-nodes are the final SSN metanodes for which we inferred a function from the analyses described here. Together, they only represent a few hundred of the sequences in mammal gut microbiomes. These metanodes also contain a few dozen genomic sequences from various bacterial phyla, including Firmicutes, Bacteroidetes and Actinobacteria, which are highly abundant in the gut microbiota (Fig. S6 , Table  S1 ). The UC1 meta-node, the U1 member of which was shown in this study to target the Man-β-1,4-GlcA disaccharide, only represents 4 % of our metagenomic dataset. The Man-β-1,4-GlcA motif is described in Nicotiana plumbaginifolia  [53] , but this tobacco plant species is not a dietary constituent for mammals. This motif also exists in bacterial lipopolysaccharides (Fig. S5 ), in particular the O-antigen polysaccharide of Shigella boydii  [54] , one of the four Shigella species considered to be major enteropathogens causing childhood diarrhoea worldwide  [55].
The UC7 and the C5 meta-nodes, which target β-1,3linked mannosides, together represent just 3 % of the metagenomic dataset. These two meta-nodes each contain promiscuous GPs (the U7 and zobellia_231 enzymes  [23] ), of which the substrates are the Man-β-1,3-Glc and Man-β-1,3-Man disaccharides. These motifs are found in some moulds  [47, 56] , and also in the lipopolysaccharides of certain pathogenic bacterial species, such as Pseudomonas aeruginosa (Fig. S5 )  [57]. Thanks to their ability to produce these particular oligosaccharides through reverse phosphorolysis, the U1 and U7 GPs characterized in this study are tools of interest for the synthesis of antigenic oligosaccharides. In this study, we thus revisited the functional diversity of the GH130 CAZy family by integrating that from mammalian gut microbiomes.
Acknowledgements The enzyme characterization was carried out using the equipment of the ICEO enzyme screening facility. ICEO is supported by grants from the  Région Midi-Pyrénées , the  European Regional Development Fund and France's Institut National de la Recherche Agronomique (INRA). This research was funded by the  European Union 's  Horizon 2020 framework programme  ( LEIT-BIO-2015-685474 , Metafluidics) and by the  Agence Nationale de la Recherche  ( ANR-16-CE20-0006 , Oligomet). A. L. is supported by  INSA Toulouse and China Scholarship Council  under the ' CSC -UT/INSA Program '. We cordially thank  Simon Charnock  and  Darren Cook (Prozomix)  for their support with enzyme production.
, 2017; Ghosh et al. , 2019). Meanwhile, other promising strategies, such as probiotics, lysins and antimicrobial peptides are in various stages of development  (Ghosh et al. , 2019). Globally, although several alternatives exist in nature, the challenge still remains to demonstrate their efficacy and their use in human and animal. Bacteriocins form a large family of antimicrobial peptides (AMP) produced by bacteria  (Klaenhammer, 1988). Their biological characteristics and activities have been deeply described in a new web-accessible database named BACTIBASE, which is freely available at the http://bactibase. pfba-lab. org web-based platform. Bacteriocins can be either unmodified or posttranslationally modified peptides, the latter thus belonging to the large family of ribosomally synthesized and posttranslationally modified peptides (RiPPs)  (Arnison et al.
Recently, a clinical trial evaluating dasatinib in combination with temozolomide and radiotherapy on newly diagnosed glioblastoma did not show promising results (NCT00869401). The current efforts in evaluating SRC inhibition potential are coupled with research in drug design to develop optimized SRC inhibitors for combinatorial approaches with radiotherapy. Such a field benefits from the current knowledge on the limitations of previously tested drugs. For example, it is now clear that pharmacodynamic issues, such as overexpression of efflux transporters P-gp at the blood-brain barrier levels, strongly affects dasatinib efficiency  [115]. Current efforts aim at the design of new SRC inhibitor drugs aiming at the optimization of combinatorial approaches with radiotherapy. A new SRC inhibitor, belonging to the pyrazolo[3¨-d] pyrimidines series (i.
Bioinformatics analyses Variants detected by targeted NGS were annotated using Ion reporter software. They were evaluated with Alamut Mutation Interpretation Software (Interactive Biosoftware, Rouen, France). Databases such as ExAC Genome browser (http://exac. broadinstitute. org), dbSNP135 (National Center for Biotechnology Information [NCBI], Bethesda, Maryland, USA, http://www. ncbi. nlm. nih. gov/projects/SNP/), ClinVar (www. ncbi. nlm. nih. gov/clinvar) and HGMD professional (www. hgmd. cf. ac. uk) were also screened. Cov'Cop and CovCopCan, interactive powerful software, were used to detect Copy Number Variations (CNV)  (Derouault et al, 2017; Derouault et al, 2020). Briefly, using the read depth value of each amplicon, these software simultaneously analyze all the patients of the run.
Detection of Structural Variant using CovCopCan We then used the new CovCopCan software, a user-friendly tool, based on the read-depth analysis of NGS data, that allows the rapid and easily detection of Structural Variants (SVs) in inherited diseases but also in Cancer  (Derouault et al, 2020). Using CovCopCan, we identified easily the presence of a heterozygous deletion in SACS gene (Figure  2A ) in comparison to a control (Figure  2B ). We could also define, thanks to CovCopCan, the boundaries of the deletion. Indeed, we could see that amplicons on exon 9 were not deleted (value around 1 in CovCopCan) and that amplicons on exon 10 were deleted (value around 0. 5)  (Figure 3A and 3B). This new SV has never been described (SV-GnomAD) and it could lead to the production of a truncated protein.
DISCUSSION We showed here the importance of complete bioinformatics analysis of NGS data to perform an accurate diagnosis. In this family, the presumed homozygous mutation c. 5744_5745delAT has been detected in SACS gene by classical variants detection software such as Ion Reporter in Patient A. This conclusion was actually not accurate. Indeed, Patient A presents in fact one allele with c. 5744_5745delAT mutation and one allele with a Structural Variation: a large deletion of SACS exon 10. This SV has been detected thanks to CovCopCan Software, a new user-friendly tool allowing the detection of Copy Number Variations (CNVs) in NGS data generated from amplicons sequencing. Few user-friendly tools are easily usable for biologists and geneticists to detect SVs, such as CNVs, in amplicons sequencing data.
| Patient follow-up and data collection For each patient, the follow-up period started at the BRAFi initiation visit, or, for patients treated with MEKi alone this started at the MEKi introduction visit. Baseline data including age, sex, previous cardiovascular history, cardiovascular risk factors, current cardiovascular treatments, tumor burden (less or more than 3 metastatic sites), previous lines of treatment for melanoma, laboratory assessment, baseline ECG and TTE were retrospectively collected during this visit. End of follow-up was the last visit before BRAFi discontinuation or at the last visit before death. Patients were censored on December 31, 2018.
Diastolic function was evaluated using 4 criteria derived from recent guidelines: 1) average E/e' >14, 2) Septal e' velocity <7 cm/s or lateral e' velocity <10 cm/s, 3) tricuspid regurgitation velocity >2. 8 m/s, 4) left atrial surface >20 cm 2 instead of left atrial volume index >34 mL/m 2 which was not recommended during the enrollment period. Diastolic dysfunction was defined as the presence of ≥3 criteria. 13 Valvular heart disease were described as recommended and considered significant if grade ≥2. 14 TTE data were retrospectively analyzed during 5 visits for patients with LVEF-D: at baseline, last visit before LVEF-D, visit with LVEF-D, next visit after LVEF-D, and at the end of follow-up. In the subgroup of patients without LVEF-D (as defined above), TTE data were analyzed only at baseline and at the last visit of follow-up.
13 C-labeled GlcChol and Cer[DS] d17. 0/16. 0 in methanol (both used as an internal standard) were added followed by a Bligh and Dyer extraction as described previously  [1, 15]. Half of the lipid extract was deacylated prior to GlcCer[S] measurement  [16]. LC-MS/MS analysis. For all experiments a Waters Xevo-TQS micro instrument was used. The instrument consisted of a UPLC system combined with a tandem quadruple mass spectrometer as mass analyzer. Acquired data were analyzed with Masslynx 4. 1 Software (Waters, Milford MA, USA). Tuning conditions and MS settings for GlcChol and GlcCer[S] in ES+ (electrospray positive) mode are as published previously  [1, 13].
Immunoblots were developed using ECL prime (GE healthcare) and imaged using a chemiluminescence detector (Vilber Lourmat). The membrane was subsequently stripped by incubating in 1X stripping buffer (200mM glycine, 0. 1% SDS, 1%Tween20, pH 2. 2) twice for 10 minutes, washed in PBST, and stained with Direct blue as per  42  to detect total protein. The blot images were quantified using Image Lab software (Bio-rad) and a one-way ANOVA statistical test was used to test for significant changes in LC3 accumulation. Details on human muscle biopsies are provided in Supplemetary Table  7. For immunohistochemistry, sections were re-cut from stored frozen muscle (-80 °C). 8 µm thick cryo-sections were air-dried and fixed in cold acetone at -20 °C for 10 min. Staining was carried out using an automated immunostainer (BenchMark XT, Ventana medical systems) as per manufacturers instructions with anti-p62 antibody (BD Biosciences).
Detected aggregates were masked using the segmented muscle tissue region to select only the aggregates within the tissue. Aggregate density was calculated as the number of aggregates per unit volume of tissue. Source code and a current build for the ImageJ/Fiji Aggregate plugin can be found at: https://gitlab. erc. monash. edu. au/mmi/aggregate. All drugs were tested in triplicate with the treatment and imaging order randomized within each replicate, and the identity of treatment blinded.
75NA), equipped with an EMCCD cooled charge-coupled camera at -50°C (Hamamatsu Photonics K. K) and driven by Volocity software version 6. 01. The volocity software version 6. 0 (Quorum Technologies) and Image J 1. 48v (National Institute of Health) software were used for processing on entire images before cropping to emphasize the main point of the image. Processing was limited to background subtraction, brightness/contrast adjustment and deconvolution. For immunoblotting, equal amounts of proteins were loaded on SDS-PAGE and analyzed by Western blot as described before  50. Protein concentrations were determined using the DC M Protein Assay Kit BioRad (#500-0116, Biorad).
Analysis of aggregates versus diffuse staining Epifluorescence images of 40 randomly chosen fields per condition were acquired with an AxioObserver Z1 system using a 40x Plan-Neofluoar 0. 6NA objective. For each field, the percentage of cells or myotubes containing aggregates and/or filaments was counted semi-automatically using the Image J 1. 48v software. Statistical calculations were performed using Prism 6. 0 (GraphPad Software) statistical software. The statistical tests used are indicated in the figure legends.
Statistical analysis GraphPad Prism and SPSS statistics packages were used to analyse data in this study. Note that the number of independent biological replicates examined for each experiment and the number of fish used within each replicate combined with the significance tests used and the associated t/F value, degrees of freedom (df) and exact p values obtained are detailed in Supplementary Tables  2 3 4 5 6. Drug screen: To identify drugs that significantly reduced protein aggregation in Tg(BAG3 P209L -eGFP) embryos a one way ANOVA statistical analysis was performed with treatment as a fixed effect and replicate as a random effect, and Dunnett's post-hoc test was used to correct for multiple comparisons. Movement assays: Outliers, identified as being more than 1. 5 times the interquartile range below the 1 st quartile or above the 3 rd quartile in each treatment group were omitted.
| Quantification of γH2AX by Flow cytometry In brief, cells were fixed in 4% paraformaldehyde (PAF), permeabilized in 0. 25% Triton X-100 in phosphate-buffered saline (PBS) for 20 min on ice, washed with PBS, incubated 20 min with blocking solution (PBS containing 10% FCS, 0. 3 M glycine and 0. 05% sodium azide) for 30 min at room temperature, and washed in PBS containing 1% FCS, 1 mM EDTA and 0. 09% sodium azide (AutoMACS Running Buffer, Miltenyi Biotech) before to be incubated in MACS buffer containing Alexa Fluor 647 Mouse anti H2AXpS139 (BD Pharmingen, clone N1-431) diluted at 1/50 or isotype APC mouse IgG1  (Miltenyi Biotech,  diluted at 1/50. Incubation was performed at room temperature in the dark for 2 hr with gentle mixing every 30 min. Fluorescence intensity of each sample was recorded on a FACS LSRFortessa™ X-20 (BD Biosciences), and the data were analyzed using FlowJo software (Tree Star).
| Cell cycle analysis Cell cycle progression was assessed using the BrdU pulse method. MDA-MB-231 cells were pulse-labeled with BrdU for 1 hr and allowed to recover for different incubation periods (0, 4, 8, 24, or 48 hr). Cells were fixed in 70% cold ethanol overnight at -20°C, permeabilized on ice in PBS-0. 5% Triton X-100 for 15 min, washed in PBS, and incubated with anti-FITC-BrdU antibody in 2% BSA in PBS. After washing with PBS, cells were incubated with an Alexa Fluor 488-conjugated secondary antibody, washed and resuspended in 0. 5 ml of PBS containing 1% FBS, 1 mg/ml RNaseA, and 50 μg/ml propidium iodide. FACS analyses were performed on a BD FACSCANTO II flow cytometer. Data were analyzed using FlowJo software (Tree Star).
| Metabolism decrease in "evolved" cells Chromatin structure change is often associated with large transcriptional modifications. Actually, transcriptome analysis revealed a major change in gene expression with a large excess of genes downregulated in 3 independent "evolved" populations as compared to three independent "naïve" populations (Table  S2 ; access to raw data in GEO; GSE144023). A similar bias to repressed expression was observed in MDA-MB-231 tumors xenografts after three cycles of AsiDNA injection  (Jdey et al. , 2019). Strikingly, metabolic pathways were significantly deregulated in "evolved" cells as compared to "naïve" cells analyzed from cell culture or from tumors. Actually, (red line) cells were allowed to grow for up to 2 weeks and counting every 2 days. Shown is the average ± SD of 14 independent cultures.
Ethics statement The manuscript, entitled 'COVID-19/acute Fanconi syndrome precedes acute kidney injury', was evaluated by the Ethical Committee of Nancy University Hospital, where this research was done. This research was carried out in accordance with current French and European ethical standards, as well as with the World Medical Association International Code of Medical Ethics. The 'Nancy Biochemical Database' is registered in the French National Commission for Data Protection and Liberties (CNIL No. 1763197v0), which supervises the protection of individuals with regard to the processing of personal data  [19].
Statistical analysis The analysis was descriptive. Quantitative data are presented as mean (6 standard devation) or median ( interquartile range). Qualitative variables were compared using the Fisher's exact test or Chi-square test when appropriate. Chi-square test for trend was used for the analysis of AKI, and to compare the number of abnormalities related to proximal tubule injury between the two groups (ICU patients group and other inpatients). Quantitative variables were compared using the Mann-Whitney U-test. All comparisons were two-sided and a P < 0. 05 was considered significant. Analyses were performed using GraphPad Prism software (San Diego, CA, USA).
Precise techniques to estimate feed intake by ruminants are critical to enhance feed efficiency and to reduce greenhouse gas emissions and nutrient losses to the environment. Using a meta-analysis, we evaluated the accuracy of the n-alkane technique to predict feed intake in cattle and sheep, and assessed the relationships between feed intake and fecal recovery of nalkanes. The database was composed of 28 studies, including 129 treatments (87 and 42 for cattle and sheep, respectively) and 402 animals (232 cattle and 170 sheep) fed at troughs, from published studies. Relationships between observed (in vivo measurement) and predicted feed intake by C31:C32 and C32:C33 n-alkane pairs were evaluated by regression. Meta-regression addressed the relationships between the difference in fecal recovery of n-alkane pairs and the error in intake estimation, as well as the amount and duration of C32 n-alkane dosing.
Literature review and dataset construction A literature search was carried out using two search engines: (1) the online databases Agricola (National Agricultural Library, U. S Department of Agriculture) and (  2 ) CAB Abstracts and Global Health on Web of Science (Centre for Agriculture and Bioscience International). Candidate publications were selected using the following keywords: n-alkanes, intake, fecal recovery, ruminant, cattle, and sheep. The initial dataset had 62 studies focusing on feed intake estimation by n-alkane pairs C31:C32 and C32:C33. Thirty-four studies were excluded because they had no information about the observed feed intake (22 studies) and the dosing procedure (7 studies). Five studies were also rejected because they have been carried out with animal species other than cattle and sheep.
After discarding these manuscripts, 28 studies were selected (19 for cattle and 9 for sheep), including 129 treatments (87 for cattle and 42 for sheep) and 402 animals (232 cattle and 170 sheep). Each study and treatment were coded by a number. The number of replicates within an experiment and standards errors of responses were included in the database. A template for data extraction was drafted, which included information about the number of replicates within an experiment, animals characteristics (species, sex, number of animals within the study, body weight [BW], age, and performance), diet characteristics (type, number of forage species, feeding levels, crude protein, digestibility, and n-alkane concentration), the procedure of synthetic n-alkane dosing (amount and duration) and fecal collection method.
Data processing For both animal species, the relationships between the observed feed intake (kg DM/d) and predicted feed intake from C31:C32 and C32:C33 n-alkane pairs (kg DM/d) were studied by linear regression. The relationship between the fecal recovery of n-alkanes and the error in feed intake estimation was also considered. For that purpose, the difference of fecal recovery for each pair of n-alkanes was calculated, as follows: DFR (%) = (FR dosed -FR natural) x 100.
Statistical analyses The meta-regression between the independent and dependent variables was analyzed using the Mixed procedure of Statistical Analysis System (SAS Inc. , Cary, NC). The independent variable was the observed feed intake (kg DM/d) while the predicted feed intake by n-alkane pairs (kg DM/d) was the response variable. For other relationships, the fecal recovery of each n-alkane and the differences in fecal recovery between the n-alkane pairs (%) were used as independent variables. They were studied with other responses such as: (1) the discrepancies in observed vs. marker-predicted feed intake estimates (%); (2) the daily amount of C32 n-alkane dosing (mg•kg of BW -1 •d -1 ); and (3) the duration of the dosing (days). The effect of animal species on the fecal recovery of each n-alkane, the discrepancies in intake estimates and the differences in fecal recovery of n-alkane pairs were analyzed by analysis of variance.
Database characteristics In the cattle database, each study included on average 11 animals with 5 replicates per treatment, a live BW that averaged 425 kg and a coefficient of variation (CV) of 45% (Table  2 ). On average, three different forages species were used for each trial, with average crude protein concentration and DM digestibility of 150 and 627 g/kg DM, respectively. The synthetic C32 n-alkane was dosed to animals during 1 to 20 d. The amount of dosed n-alkane averaged 540 mg/d and ranged between 177 and 1,122 mg/d with a CV of 52%. The n-alkane concentrations of the forage diet for cattle averaged 251, 10, and 91 mg/kg DM for C31, C32 and C33, respectively. On average, 12sheep were used for each trial and five replicates per treatment, with a live BW that averaged 39 kg, and ranged from 30 to 65 kg, with a CV of 27% (Table  3 ).
Robustness and Intersample Contamination The assay was designed to be performed on 50 ng of extracted DNA. However, the influence of lower and higher DNA amount on the performance of the analysis was assessed. The results are reported in Table  3. It appears that the genotypes can be accurately determined when DNA sample amounts range from 25 to 100 ng. Outside this range, the intensity of the signal does not meet the acceptance criteria to interpret migration fragment data (peak height < 100 units of intensity or saturation of the signal). No influence of the quality of the DNA was observed. Indeed, genotyping was successfully performed in our cohort, whose absorbance ratio ranged from 0. 35 to 2. 3 and 1. 5 to 2. 1 for ratios of 260/230 nm and 260/280 nm, respectively. Moreover, no intersample contamination was observed since no signal was detected at the position of the blank samples inserted between the DNA samples (data not shown).
Genotyping and Fragment Analysis The PCR products were denatured with deionized formamide (Thermo Fisher Scientific, Illkirch, France) and separated on an ABI 3130 Genetic Analyzer (Applied Biosystems TM /Thermo Fisher Scientific, Illkirch, France). GeneScan™ 500 ROX™ (Applied Biosystems TM /Thermo Fisher Scientific, Illkirch, France) was used as a dye size internal standard. Data were processed using the GeneMapper ® 4. 0 software (Applied Biosystems TM ). We defined the acceptance criterion of the genotyping results after migration on the sequencer as follows: the height of the signal of each fragment should be higher than 100 (intensity unit) and lower than 7500 (intensity unit) to avoid saturation, and the length of each fragment should not differ from a +/-1 base pair from the theoretical length of the fragment.
Internal Control Samples In order to check the success of each set of experiments during method development and validation, DNA samples of known genotypes were used as homozygous wild-type, heterozygous, and homozygous variant internal controls. These samples came from a DNA bank of human DNA whose genotypes were previously confirmed by Taqman TM and Sanger sequencing. Homozygous variant control samples were not available for TPMT rs1800462, NUDT15 rs116855232, and the four DPYD SNPs since these genotypes are very rare in the population. Moreover, at the time of the method development, we did not have enough amount of DNA sample in our bank that matched with the genotype heterozygous for DPYD rs55886062 (low-frequency variant). Thus, this control was synthetized by performing a subcloning experiment as described in Supplementary Data 1.