dataesr/scientific-paragraphs-categorization huggingface dataset:
The necessary scientific validation of traditional uses implies the isolation of the main bioactive compounds by successive fractionations using chromatographic techniques and biological activity testing (bio-guided isolation). Such an approach has evidenced interesting activities for Piper spp. as antiinflammatory, antiparasitic, antibacterial, etc. (Mgbeahuruike et al. , 2017; Durant-Archibold et al. , 2018). Even if bio-guided fractionation is still used with some success in the natural product chemistry field, current trends involve streamlining the cost, effort, and time  (Vásquez-Ocmín et al. , 2022). Metabolomics is a holistic approach allowing rapid detection and putative identification (i. e. , annotation) of numerous metabolites, along with data mining on multiple datasets. Metabolomics aims to comprehensively map all biochemical reactions in a given system and has become a key to deciphering their biological roles, hence becoming mainstream in natural product chemistry and drug discovery.
Liquid chromatography and mass spectrometry data mining HPLC-MS analyses Extracts were analyzed by liquid chromatography performed on an Agilent 1260 series HPLC coupled to a 6530 QToF (Agilent Technologies). Chromatography separations were performed on a XSelect CSH C18 column, 130Å, 2. 5 µm, 2. 1 × 75 mm -(Waters). The mobile phase comprised water (0. 1% formic acid) A) and acetonitrile (ACN) B). A stepwise gradient method at a constant flow rate of 0. 35 mL/min was applied as follows: 5%-100% B (0-9. 5 min), 100% B (4. 5 min) and 4 min equilibration at 5% B. The mass spectrometer settings were: positive ESI mode, 50-3200 mass range calibration, and 2 GHz acquisition rate. Ionization source conditions were drying gas temperature 325 °C, drying gas flow rate 10 L/min, nebulizer 35 psig, fragmentor 150 V, and skimmer 65 V.
Data processing For untargeted metabolomics, the LC-MS data were processed according to the MSCleanR workflow  (Fraisier-Vannier et al. , 2020; Vásquez-Ocmín et al. , 2021b). Briefly, a batch in positive ionization (PI) was processed with MS-DIAL version 4. 90  (Tsugawa et al. , 2015). MS1 and MS2 tolerances were set to 0. 01 and 0. 05 Da, respectively, in centroid mode for each dataset. Peaks were aligned on a QC reference with an RT tolerance of 0. 2 min, a mass tolerance of 0. 015 Da, and a minimum peak height detection at 1 × 10 5. MS-DIAL data was deconvoluted together with MS-CleanR by selecting all filters with a minimum blank ratio set to 0. 8 and a maximum relative standard deviation (RSD) set to 40. The maximum mass difference for feature relationship detection was set to 0. 005 Da, and the maximum RT difference was set to 0.
025 min. Pearson correlation links were used with a correlation ≥0. 8 and a p-value significance threshold of 0. 05. Two peaks were kept in each cluster for further database requests and the kept features were annotated with MS-FINDER version 3. 52  (Tsugawa et al. , 2016). The MS1 and MS2 tolerances were set to 5 and 15 ppm, respectively. The formula finder was exclusively based on C, H, O, and N atoms. Three levels of compounds annotation from several sets of data were carried out. Metabolite annotation at level 1 using MS-DIAL: i) the experimental LC-MS/MS data of 500 compounds (retention time, exact mass and fragmentation) were used as references; ii) the Mass spectral records   Mass spectra similarity networking was carried out from PI mode using MetGem  (Olivon et al. , 2018)  on the final annotated.
Statistical analyses The final annotated untargeted metabolome feature matrix and biological assay results datasets were analyzed using the R package MixOmics (http://mixomics. org/), which is dedicated to the integrative analysis of 'omics' data (Le  Cao et al. , 2016). Biological assays results expressed in IC 50 were transformed in pIC 50  ]) for further statistical correlation analysis. MIC values were log transformed. The LC-MS dataset (m/z × RT × peak area) was normalized to total ion chromatogram and scaled to unit variance. A vertical integration approach has been afforded to leverage on multiplexed measurements for the same extract  (González et al. , 2008). To highlight the overall correlation between chemical fingerprints and biological assays. A regularized Canonical Correlation Analysis (rCCA) was done using a cross validation approach for tuning regularization parameters.
Group 2 is composed of 9 features  (4, 6, 7, 16, 53, 63, 65, 77, and 117). This group was selective on Leishmania (all strains, both axenic and intramacrophagic). We also performed a relevance network (RN) analysis on the same datasets to verify and complete the CIM results (Figures  2-B ). RN showed two main clusters of features linked to the activity, the same as in the CIM. The LC-MSMS molecular network (Figure  1 ) allowed to determine that six features identified in the Group 1 belong to the alkaloids class, while others are mostly self-loops (i. e. , compounds not having structurally-related analogs in the extract) belonging to varied phytochemical classes. In the case of Leishmania-specific compounds (Group 2), they mostly belong to the polyketides or shikimates and phenylpropanoids classes, and are found only as self-loops or only related to one compound and not correlated to any activity (i.
While this terminology would initially direct the sample collection, we took great care of properly identifying the species upon collection. In two  Frontiers in Pharmacology frontiersin. org 13 cases, we could not fully ascertain the species and further taxonomic examination is underway. Chemical profiling of natural extracts can be readily obtained, but for metabolomic purposes, data need to be 'preprocessed' (peak picking, alignment, clustering, integration and normalization) to obtain a clean dataset able to provide meaningful information upon statistical analysis. The large abundance and complexity of variables are also challenging and require to apply an appropriate statistical method to answer a specific biological question  (Hervé et al. , 2018). Few metabolomic studies on Piper species using NMR  (Yamaguchi et al.
, 2011; Uckele et al. , 2021)  or LCMS have been reported so far  (Vásquez-Ocmín et al. , 2021a). The Piper genus is a good model to apply our framework for two reasons: i) Piper species are particularly abundant in Peru (~260 according to www. tropicos. org), many of them used in traditional medicine; ii) many studies, including numerous phytochemical ones, were carried out on this genus (~9,000 results found in www. webofscience. com for "Piper", consulted on 1 July 2022), allowing a good metabolome coverage. We propose in this work a computational statistical analysis to integrate two heterodimensional datasets: the features (compounds) obtained by LC-MSMS analysis of Piper extracts (Supplementary Table  S3 ), and the in vitro biological activity of these extracts on parasites, bacteria and mammalian cells (Table  1 ; Supplementary Table  S2 ), with the aim to outline most active compounds.
To leverage on this multiplexed approach, we applied a regularized Canonical Correlation Analysis (rCCA). This method aims to extract correlated information by maximizing their correlation via canonical variates between two datasets acquired on the same samples (vertical integration). The results of rCCA model were displayed using Clustered Image Maps (CIM) to highlight the correlation level of variables from all datasets, ordered through unsupervised clustering on both samples and compounds simultaneously  (González et al. , 2012). Another approach for displaying net-like correlation structures between two data sets is to use Relevance Networks (RN). This method generates a graph where nodes represent variables, and edges represent variable associations  (Butte et al. , 2000). Given an appropriate threshold, the RN highlights main correlation between both datasets (Figures  2-B ).
(Vásquez-Ocmín et al. , 2023)zoal and cytotoxicity activities of Piper extracts. M = methanol; H = hexane; D = methylene chloride (D stands for dichloromethane); HA = hydroalcoholic; Aq = aqueous; NT = not tested. *Speciesshowingnoreference in phytochemical literature on Web of Science and PubMed. **Extractspreviouslytested(Vásquez-Ocmínet al. , 2021a)(the plants in this work come from different collection 331 site). L = leaves; L&S = Leaves and stems; AP = aerial parts; "" = species with temporary botanical name (these species need more taxonomical 332 studies). DIAL, MONA (MassBank of North America), and GNPS (Global Natural Product Social Molecular Networking) databases were used for spectral match applying a dot product score cut-off of 800. Metabolite annotation at level 2 was prioritized according to: i) a search would be made using MSFinder for a match with compounds identified in the literature for the Piper genus (genus level) and Piperaceae family (family level) (Dictionary of Natural Products version 28.
Acknowledgments Authors are indebted to the communities cited in this work for their essential contribution in order to spread their ancestral knowledge. The authors thank IRD the  French National Research Institute for Sustainable Development (IRD) ,  UMR 152 PHARMADEV ,  IRD-UPS (Toulouse, France)  for the post-doctoral fellowship to PV-O (contract number  04077858 ). The authors thank  MINEDU (Ministerio de Educación), Lima, Peru, convenio MINEDU-UNAP  ( Decreto Supremo   146-2020 ,  EF/Resolución Rectoral N °1312-2020- UNAP, 9/12/2020 ). We also appreciate the important collaboration of  Juan Celedonio Ruiz (Herbarium Amazonense (AMAZ) de la Universidad Nacional de la Amazonía Peruana (UNAP), Iquitos, Perú ). The authors are also grateful to  Amélie Perez  ( MetaboHUB-MetaToul-Agromix, LRSV, Auzeville-Tolosane ),  Guillaume Cabanac  ( IRIT, Toulouse ), and  Rizwana Zaffaroullah  ( CNR du Paludisme, AP-HP, Hôpital Bichat -Claude Bernard, F-75018 Paris, France ).
2, CRC Press) based on exact mass and in silico fragmentation. For metabolite annotation level 3, a search was made using MS-FINDER for a match with natural compounds included in their databases embedded (PlantCyc, ChEBI, NANPDB, COCONUT, and KNApSAcK) (generic level)(Vásquez-Ocmín et al. , 2023). Frontiers in Pharmacology Species, Region (part tested) Extract (code for metabolomic analyses) P. falciparum 3D7 strain, IC 50 ± SD, µg/mL L. donovani LV9 strain (axenic amastigotes), IC 50 ± SD, µg/mL L. donovani LV9 strain (intra-macrophagic amastigotes), IC 50 ± SD, L. amazonensis (axenic amastigotes), IC 50 ± SD, µg/mL L. amazonensis (intra-macrophagic amastigotes), IC 50 ± SD, µg/mL L. braziliensis (axenic amastigotes), IC 50 ± SD, µg/mL L. braziliensis (intra-macrophagic amastigotes), IC 50 ± SD, µg/mL Trypanosoma brucei gambiense IC 50 ± SD, µg/mL HUVEC CC 50 ± SD, µg/mL RAW 264.
Compounds 2-5 and 6-9 were synthesized according to a previously reported methodology from diethyl 2-oxo-2-phenylethylphosphonate 1 (151 µL, 0. 5 mmol) and primary amine (0. 5 mmol)  [54]. The reaction mixture was refluxed using a Dean-Stark apparatus. The obtained NMR data based on 1 H and 31 P{/ 1 H} NMR for 2-4a,b and 6-8a,b are identical with those reported in the literature  [54].
Catalytic activities reported for the most diversified (blooming) plant CYP families. Frequency refers to the number of enzymes investigated and shown to metabolize a class of compounds. N. B. the table is exclusively based on the currently available erda. dk/public/vgrid/PlantP450/ database that is focused on plant physiological activities, but not exhaustive regarding metabolism of xenobiotics. The database will be updated in the coming months in this respect. References of the publications reporting activities of the members of each family can be found in the database.
Regarding additional thermal properties, Figure  2  plots the thermal stability of the copolymers and terpolymers based on PFP, VDF and a third comonomer versus the molar mass assessed by size exclusion chromatography or NMR. As expected, these data show that the thermal stability of the copolymers increases with molar mass. mass assessed by size exclusion chromatography or NMR. As expected, these data show that the thermal stability of the copolymers increases with molar mass. It was also worth plotting the evolution of the thermal stability versus the comonomer content in the copolymer. Figure  3  indicates that the thermal stability increases with increasing VDF content but decreases with either HFP or PFP units in the copolymers. As shown above, this feature might be linked to the molar mass, since VDF yielded higher ones than HFP or PFP did.
It was also worth plotting the evolution of the thermal stability versus the comonomer content in the copolymer. Figure  3  indicates that the thermal stability increases with increasing VDF content but decreases with either HFP or PFP units in the copolymers. As shown above, this feature might be linked to the molar mass, since VDF yielded higher ones than HFP or PFP did. Molecules 2023, 28, x FOR PEER REVIEW 7 of 24 mass assessed by size exclusion chromatography or NMR. As expected, these data show that the thermal stability of the copolymers increases with molar mass. It was also worth plotting the evolution of the thermal stability versus the comonomer content in the copolymer. Figure  3  indicates that the thermal stability increases with increasing VDF content but decreases with either HFP or PFP units in the copolymers.
Data Availability Statement: Not applicable. Acknowledgments: All the companies [Great Lakes (now Chemtura), Solvay, Elf Atochem (now Arkema), Tosoh Finechemical Corp. and Akzo Nobel (now Nouryon)] which have contributed to this work by providing us with free materials are acknowledged. The authors would like to thank the Great Lakes/Chemtura Company for its financial support. BA is grateful to the French Fluorine Network (GIS).
Particle size analysis Particle size distributions (PSDs) were measured using the laser diffraction method (Malvern Mastersizer 3000). About 7-10 g sample taken from the segregation tests was introduced into a dry dispersion unit and formed five repeated measurements. For the measurement settings, the air dispersion pressure was 2. 5 bars with a vibration feed rate of 40% at a gate gap of 1. 5 mm for all the tests. The particle volume distribution was calculated using the 'general-purpose model' in the Mastersizer software. PSD of each sample was measured with all the repeats, and the average with standard deviation was reported and used for data analysis. With this method, volumetric concentrations of the PSDs were given, and particle sizes at D 10 , D 50 and D 90 were also found.
, Santa Clara, CA). The separation of QUIN was carried out with a DB-5MS column, 0. 25 µm film thickness, 0. 25 mm × 30 m capillary column (Agilent Technologies Inc. , Santa Clara, CA) for 12 min. Concentrations of QUIN were analyzed using Agilent GC/MSD ChemStation software (Edition 02. 02. 1431). A series of deuterated and non-deuterated standards for QUIN were used for a six-point calibration curve to interpolate the quantity of the sample readout.
Chemical fractionation The cPE extract was first analyzed by HPLC/MS and the major compounds present in this fraction isolated by semi preparative HPLC to yield compounds (1) to (7). Dried extracts were solubilized in methanol at 10 mg/ml for analytical and semi preparative experiments, the injected volume being different, and filtered on a 0. 45 μM PTFE filter before HPLC analysis. The cPE samples were analyzed by HPLC-UV-DAD (Waters 2695) at different wavelengths, using a RP Nucleodur C18ec column (250 by 4. 6 mm, 5 μm particle size, Macherey Nagel) column and using water plus formic acid 0. 05% as solvent A, and acetonitrile as solvent B plus formic acid 0. 05%, and coupled with mass spectrometry (MS) using an ion trap Bruker Esquire HCT Ultra mass spectrometry instrument equipped with an electrospray ion source in positive and negative mode (data were viewed by using Hystar Bruker software).
Structural elucidation Chemical structures were determined by 1D NMR 1 H (600 MHz), 13 C (150 MHz) and 2D homo using the NMR equipment from Brucker with the following parameters: 600 MHz Avance III, equipped with a 5 mm BBFO + probe, and hetero-coupling methods (COSY, HSQCed, HMBC and NOESY) in CDCl 3 at 298 K and data were compared to those found in the literature. The numeration for the carbon atoms is shown in Figure  4  for coleon U (1) and is the classical one used for abietane diterpenes. The results obtained for 1 H and 13 C NMR are gathered in tables 2 and 3. δ in ppm (s: singlet, d: doublet, t: triplet, q: quadruplet, quint: quintuplet, sept: septuplet, m: multiplet, l: large, J in Hz, number of protons). Mass spectra were in accordance with the structures found (Table  1 ).
Acknowledgments The authors are thankful to  Pierre CABAILLON  for sharing initial information on traditional plants used in New Caledonia and for the selecting process of plants of interest. We are thankful to  Gaëtan HERBETTE  from the analytical platform Spectropole,  FR1739 , at  Aix-Marseille University , for NMR experiments. We also thank  Marie-Claude QAENG  and  Julie CAGLIERO.
Funding This research was funded by the  "Fonds de cooperation économique, sociale et Culturelle pour le Pacifique" of "Fonds Pacifique " (Project  1707 ,  N °SPP 28-1-2017 ) supported by the  French Ministry of Foreign Affairs , the  French Ministry of Higher Education, Research and Innovation (MESRI) , the  Institut Pasteur of New Caledonia (IPNC)  and the  Pasteur Network. Prof Guillemin  is supported by the  National Health and Medical Research Council (NHMRC) , Fellowship # APP1176660 , and by  Macquarie University. MM position is financed by the  Government of New Caledonia.
Herbarium specimens were studied either by visiting and/or through loans from the herbaria listed above. Specimens were examined using a dissecting microscope. For accurate citation of herbarium specimens, after the herbarium code we cite the barcode number; when no barcode number was available on the specimen, we cite the accession number preceded by "No. " All specimens cited have been examined, unless the herbarium code is followed by "n. v. " (not seen). High-resolution digital images of Piperaceae original specimens collected by Raddi in Rio de Janeiro are available from the authors (e-mails: georgeazevedo08@gmail. com, piero. delprete@ird. fr, riccardomaria. baldini@unifi. it).
Piper scutatum The morphological characters described in the protologue and the features of the specimens clearly show that this name is synonymous with Piper scutifolium Yunck. In addition, the illegitimate later homonym Piper scutatum Willd. was placed in synonymy under Pothomorphe peltata (L. ) Miq. (now recognized as Piper peltatum L. ) by  Yuncker (1973: 145). Notes. -Because Raddi's personal herbarium is preserved at PI, the only original specimen there, mounted on two sheets with accession numbers 043386 and 043387, is here designated the lectotype of this name. Raddi (1828: 4)  described Piper scolopendrifolium Raddi as a plant with obliquely cordate-lanceolate, very long, glabrous leaves. The original specimens at FI and PI and Raddi's description correspond to P. truncatum Vell. (Vellozo, 1829: 25) , which is a common species in the state of Rio de Janeiro.
mss1095062_061, which is here designated the lectotype of this name. Notes. -At PI is preserved an original specimen of Piper fluminense Raddi, mounted on two sheets, with accession numbers 043382 and 043383, numbered "2" and "1", respectively, in pencil. On sheet number 1 (Fig. 1 ), with accession number 043383, is affixed a label handwritten by Raddi "Piper (fluminense), foliis ovato-oblongis acuminatis utrinque glaberrimis basi subaequalibus, petiolis subpollicaribus canaliculatis basi vaginatibus, spadicibus oppositifoliis erectis foliis dimidio brevioribus. nob. " This is the same description that was published by Raddi. Sheet number 2 (Acc. No. 043382) is without label, and kept together with sheet number 1. This specimen, mounted on two sheets, is here designated the lectotype of Piper fluminense Raddi.
(Arias & al. , 2006). Notes. -At PI is preserved an original specimen, mounted on two sheets, with accession numbers 043372 and 043373, numbered 1 and 2 in pencil, respectively. On sheet number 1 is affixed a small label handwritten by Raddi "Piper variabile. nob. " Sheet number 2 is without a label, and kept together with sheet number 1. On those two sheets are present small portions of stem with a few leaves, and two of them, on sheet number 2, have a small inflorescence. This specimen, mounted on two sheets, is here designated the lectotype of Piper variabile Raddi. In FI there are four specimens, with barcodes FI055276, FI055277, FI055278 and FI055279. On each of them there is a branch with a few leaves, and a label handwritten by Parlatore "In Brasilia legit Cl. Raddi. " These specimens are isolectotypes.
Piper impunctatum -"[V]icinanze di Mandiocca [from previous species]" (near Fazenda Mandiocca), "Similissimo alla specie antecedente, dalla quale differisce soltanto per la presenza di una quantità di peli morbidi, che si trovano sparsi sulla pagina inferiore delle foglie, e sul loro peziolo" (Very similar to the previous species [Piper impunctatum Hoffmanns. , nom. illeg. = P. divaricatum G. Mey. , see above], from which it differs only by the presence of soft hairs on the leaf abaxial side and on the petioles). Notes. -For this taxon, Raddi (1828: 5) provided the following description "foliis lanceolato-acuminatis, integerrimis, supra glabris, subtus petiolisque villosus-hirtis, basi subaequalibus; spadicibus oppositifoliis, gracilibus. " After an exhaustive search in all herbaria studied, we were able to find only one specimen in PI, accession number 043375, without label, and constituted by just one leaf.
Vi cresce all'altezza di circa otto piedi: egli è ramosissimo, e i suoi rami sono eretti" (It is found in the surroundings of Rio de Janeiro, but not frequently. There, it grows to the height of about 8 feet  [2. 4 m]: it is much-branched, and its branches are erect). Notes. -Raddi (1828: 6) copied word for word the original description of Piper hoffmannseggianum Schult. Raddi characterized this species as a plant about 2. 4 m tall, with glabrous stems, lanceolate, acuminate, concolorous leaves, and shortly pedunculate, leaf-opposed spikes. In synonymy, he included the illegitimate name P. citrifolium Link (Jahrb. Gewächsk. 1(3): 63. 1820; non P. citrifolium Lam. 1791). Specimens of this gathering are in PI and FI. At PI there is a specimen, mounted on two sheets, with accession numbers 043369 and 043370, numbered "1" and "2".
[…]" (It grows in the very shady forests of the Serra dos Orgãos. Its stem is wider than a writing quill; the basal portion is repent, with roots at each internode, which fix the stem on the soil, the distal portion raises obliquely to find the nearby plants, on which it climbs and holds itself). Notes. -Raddi characterized this species as a plant with the basal portion lying on the ground and the distal portion climbing on surrounding vegetation, with terete, glabrous stems, sub-rotund-ovate, basally cordate, apically acuminate, 9-veined, pellucid-punctate, subcoriaceous, glabrous leaves, and leaf-opposed spikes. Three sheets of Piper marginatum Jacq. are present at PI, which should be treated as two separate specimens. The first specimen is mounted on two sheets, with accession numbers 043363 (numbered "1"), and 043362 (numbered "2").