dataesr/scientific-paragraphs-categorization huggingface dataset:
8 s, an acquisition time of 285 ms in direct dimension and 36 ms in indirect dimension. The same mixing time of 300 ms was used for TOCSY and NOESY experiments. To correlate 1 H and 13 C resonances, 2D heteronuclear experiments (1 H-13 C HSQC, 1 H-13 C HMBC) were performed with scan number between 16 and 24 scans, a proton spectral window of 3. 6 kHz, a carbon spectral window of 17 kHz and 22 kHz, a relaxation delay of 1. 3 s and 1. 8 s, an acquisition time of 285 ms in direct dimension and 8 ms or 6 ms in indirect dimension. For 2D HSQC, delays were optimized for a 145 Hz coupling constant ( 1 J CH ) and for 2D HMBC, a coupling constant of 8 Hz was used for long distance correlation. All NMR spectra were processed by using the TopSpin software (Bruker, Wissembourg). A Lorentzian noise filtering respectively 3 Hz and 0.
FTIR spectroscopy analysis Structural identification was confirmed by IR spectroscopy. Briefly, no sample preparation was necessary for Fourier Transform Infrared Spectroscopy (FTIR) measurements. The composition was examined by an FTIR (Nicolet Summit (Thermo Fisher, MA, USA)) spectrometer operating in Attenuated Total Reflectance (ATR) mode through an integrating sphere by the Nicolet 6700 FTIR device. The signals were recorded between 4000 and 500 cm -1 with a resolution of 4 cm -1. Spectrometer diagnostics and acquisition of spectroscopic data were performed by OMNIC Paradigm software (Thermo Fisher, MA, USA).
Liquid chromatography-high-resolution mass spectrometry parameters As previously published  [10] , the UPLC-HRMS system consisted of an Acquity I class system (waters, USA) coupled to a Xevo XS G2 QTOF analyzer (Waters, USA) using positive and negative mode electrospray ionization and controlled with Unifi 1. 9 software. Chromatographic separation was performed on an ACQUITY HSS C 18 column (150 ×2 mm, 1. 8 µm, Waters). The mobile phase was composed of solvents A (ammonium formate buffer 5 mM, pH 3) and B (acetonitrile in 0. 1% v/v formic acid). The column was maintained at 50 °C and a gradient elution was used at a flow rate of 0. 4 mL/min: 13% of B held until 0. 5 min, increasing to 50% at 10 min, then to 95% at 10. 25 min, and finally held until 12. 25 min, then return to initial condition in 0.
25 min until 17 min. The injection volume was 2 μL. Data were analyzed with HighResNPS® and Waters® databases for over 3500 toxicologically relevant drugs, NPS and metabolites that included protonated molecules and fragmentation and chromatographic retention time data. Criteria used to identify compounds included 5 ppm as exact mass error of the precursor ion as well as product ions and + /-0. 5 min as tolerance in retention time for the precursor ion.
MXPr metabolism exploration 3. 5. 1. In silico metabolite identification  [11]  Data was analyzed with Unifi software (Waters, Manchester, UK). A software algorithm (MetaboLynx) was used to predict in silico biotransformations. Using the available data on the metabolism of related substances, sets of theoretically possible biotransformations (including possible hydroxylation, N-dealkylation, and glucuronidation) were created based on the structure of the drug. The automated metabolite profiling process was completed using the fragmentation interpretation software tool MassFragmentTM 4. 1 (Waters) to enable software-driven assignment of metabolite structures from fragmentation patterns. The automated approach is driven from structural knowledge of the parent molecule using chemically intelligent algorithms which perform cleavage of the molecule in silico and identify possible functional groups.
Cell culture supernatants were removed and frozen at -20 °C until analysis (for 2 weeks at the most). HLM incubate samples were analyzed using the LC-HRMS method described above. The LC-HRMS-acquired data of HLM incubates were subsequently cross-checked with in silico predicted biotransformations. Criteria for identification of the targeted compounds included 5 ppm as exact mass error of the precursor ion, as well as product ions, and ± 0. 25 min as tolerance in retention time for the precursor ion.
Toxicological analysis Initial toxicological screening tests by LC-HRMS identified oxazepam, nordiazepam, norbuprenorphine, and N-ethylhexedrone. One large peak did not match with any substance present in the large available databases. The addition of the MXPr compound identified by NMR and IR spectroscopies and the retrospective urine analysis by LC-HRMS identified the unknown peak as MXPr. Hair analysis (Table  1 ) provides a useful history of past drug use, but the interpretation of hair concentrations must be done with caution. Hair analysis determined the molecules to which the patient had been exposed during the four months after hospitalization. It showed the presence of various illicit psychoactive substances and confirmed that the patient was a polydrug user. The substances identified in the hair specimen were not identified in the dichloromethane and water washes, suggesting no external contamination  [20].
Methods This review was performed in the databases Pubmed (https://pubmed. ncbi. nlm. nih. gov/advanced/, accessed on 10 March 2020), and Scopus (https://www. scopus. com/home. uri, accessed on 10 March 2020). Considering that the search for polymer-based works results in over 80,000 published papers, some criteria have been adopted. MeSH terms were used as a search strategy for a more accurate search; since a MeSH term for "polymer blend" (and its derivatives) could not be found, the following MeSH terms and their intra-terms were used: [polymers], [drug delivery systems (delivery system, drug), (drug targeting), (targetings, drug)], [administration, ophthalmic (ophthalmic administration), (administration, ocular), (ocular administrations)]. The research was carried out until April 2021, and a filter for publications from the last 5 years was also applied.
In fact, it is precisely the difficulty in finding materials that meet all the requirements as a viable release system that leads to the search for alternatives. The association of polymers occurs solely in a physical form, without chemical reactions, leading to a gain in properties compared to pure materials. In the works presented in this article, different gains with the use of blends are reported, from the increased efficiency of drug encapsulation to greater viability and cell adhesion, not to mention a better modulation of drug release rate. The search for "polymer blends" in the Pubmed and Scopus databases generates numerous results; however, they correspond to only approximately 2% of the number of results obtained by searching for "polymers". When the search is for "polymer blends for ophthalmic use" (or other corresponding terms), the number of results is usually fewer than 20 papers.
The study was approved by the Ethics Committee of Paris, Ile-de-France (CPP IDF IV IRB 00003835) and was registered on the clinicaltrials. gov website (NCT01569347, Responsible party: Assistance Publique-Hôpitaux de Paris). From the whole sample (418), 242 Caucasian subjects without primary schizophrenia disorders were selected (57. 9%) (for subject selection details, see Supplementary Material S4). Chronic psychotic disorders were assessed using the French version of the Diagnostic Interview for Genetic Studies (DIGS)  (Nurnberger et al. , 1994) , and ancestry was defined on the basis of genetic proximity to Caucasian populations. To do so, we performed a multidimensional scaling (MDS) analysis on the genotype data anchored by the 1000 Genomes panel as described by  Marees et al. (Marees et al.
Data collection Trained investigators interviewed each patient once in this crosssectional study, collecting retrospective lifetime data. The validated French version of the SAPS-CIP scale  (Cubells et al. , 2005; Vorspan et al. , 2009)  was used for the CIPS assessment, with the instruction to focus on psychotic symptoms that would occur immediately after cocaine intake during the worst lifetime period of misuse. This scale explores nine types of delusion symptoms, four types of behavioural disturbances, and four types of hallucinations (auditory, visual, tactile, and olfactory hallucinations). The severity of each dimension was scored from 0 to 5. The global score of the SAPS-CIP scale, which ranges from 0 to 15, is the sum of the three dimension scores  (Cubells et al. , 2005). Additional variables related to cocaine use and lifetime use of other drugs were also collected.
Genetic analysis Genomic DNA was extracted from peripheral blood. Genotyping was performed for 416 (from 418) patients in two waves: on the BeadChip Illumina Infinium PsychArray 24 v1. 0 chip in 2015 for the first included subjects (571 054 Single Nucleotide Polymorphisms (SNPs) and single indels), then on the BeadChip Illumina Infinium PsychArray 24 v1. 1 chip in 2017 for the following 316 patients (593 260 SNPs and single indels). Overall, 557 581 variants remained after merging the two genotype waves. Genetic imputation was performed on the Michigan Server (https://imputationserver. sph. umich. edu/index. html) (Das et al. , 2016)  from 334 975 autosomic SNPs selected after quality control on European ancestry samples. The final number of variants on the imputed data was of 7 527 426. According to the list proposed by  Brousse et al.
Cocaine dependence as a dichotomous variable was not included to avoid multicollinearity; thus, the maximum variance inflated factor (VIF) was 1. 33 among all included variables (cf. supplementary material S3). Due to missing data, this analysis was performed on only 172 subjects. All analyses were performed using R version 3. 6. 0 (R Core Team, 2019) and the glmmTMB package for the zero-inflated model fit  (Brooks et al. , 2017)  and the bigsnpr package for SNP clumping  (Privé et al. , 2018). Multiplicity correction was performed using the Bonferroni method for non-genetic and genetic associations. An association was considered significant if the corrected p-value was < 0. 05.
-H. ZERDAZI wrote the first draft of the manuscript. E-H. ZERDAZI, E. CURIS, I. KOUSIGNAN, and L. BOUMENDIL, contributed  to the statistical analysis, E-H. ZERDAZI, E. KARSENTI, R. ICICK, M. FORTIAS, P. BATEL, O. COTTENCIN, C. ORIZET, A. GAY, P. COEURU, A. DESCHE-NAU, P. LACK, D. MOISAN, A-L. PELISSIER-ALICOT, J-B. TRABUT, G. BROUSSE, and F. VORSPAN collected the data. E. VICAUT, J-P. LEPINE, F. VORSPAN, G. BROUSSE, and V. BLOCH designed the study, F. BELLIVIER, N. PRINCE, J-L. LAPLANCHE, C. MARIE-CLAIRE and R. ICICK participated in the genetic analysis. All authors have significantly contributed to and approved the final version. Role of funding sourcesPSYCHOCOKE study was funded by the Ministère Français des Solidarités et de la Santé, Programme Hospitalier de Recherche Clinique (PHRC National 2010: AOM10165).
The Délégation de la Recherche Clinique et du Développement, France (DRCD) from the Assistance Publique -Hôpitaux de Paris, France (APHP) endorsed the study. None of the funders had any role in the design of the study, in the present analyses, or in the writing of the manuscript. Furthermore, F. V. received grants from the ANR (ANR-13-SAMA-0005-01 and ERANET-Neuron Joint Transnational Call for 'European Research Projects on Mental Disorders 2013' (ANR-13-NEUR-0001-03), and ERANET-Neuron Joint Transnational Call for 'European Research Projects on Synaptic dysfunction 2017' (ANR-17-NEU3-0002-05) and from the Labex BioPsy, a French state fund managed by the ANR within the Investissements d'Avenir programme under reference ANR-11-IDEX-0004-02. F. V. also received funding from the Assistance Publique -Hôpital de Paris, INSERM and Université de Paris in the name of FHU NOR-SUD (Network of Research in Substance Use Disorders).
E -H. ZERDAZI wrote the first draft of the manuscript. E-H. ZERDAZI, E. CURIS, I. KOUSIGNAN, and L. BOUMENDIL, contributed  to the statistical analysis, E-H. ZERDAZI, E. KARSENTI, R. ICICK, M. FORTIAS, P. BATEL, O. COTTENCIN, C. ORIZET, A. GAY, P. COEURU, A. DESCHE-NAU, P. LACK, D. MOISAN, A-L. PELISSIER-ALICOT, J-B. TRABUT, G. BROUSSE, and F. VORSPAN collected the data. E. VICAUT, J-P. LEPINE, F. VORSPAN, G. BROUSSE, and V. BLOCH designed the study, F. BELLIVIER, N. PRINCE, J-L. LAPLANCHE, C. MARIE-CLAIRE and R. ICICK participated in the genetic analysis. All authors have significantly contributed to and approved the final version. Role of funding sourcesPSYCHOCOKE study was funded by the Ministère Français des Solidarités et de la Santé, Programme Hospitalier de Recherche Clinique (PHRC National 2010: AOM10165).
" AMPs are synthesized by virtually all living organisms, from bacteria to humans via plants. AMPs represent the first line of defense against invading pathogens, being a key part of the innate immune system. AMPs are either ribosomally synthesized oligopeptides or non-ribosomally synthesized peptides. In the latter case, peptides are assembled by multimodular enzymes designated as non-ribosomal peptide synthetases (NRPS). Several regularly updated databases such as APD3  (26) , the Collection of AMPs (CAMP)  (27) , the Database of Antimicrobial Activity and Structure of Peptides (DBAASP)  (28) , or the Data Repository of AMPs (DRAMP)  (29)  provide information on sequences, structures, activities, or clinical status of thousands of AMPs identified so far. Antimicrobial peptides are usually 10-50 amino acids long and lower than 10 kDa, and they contain a composition rich in cationic and hydrophobic amino acids.
The online quantitative survey was undertaken by IPSOS. Three thousand women aged 16-50 were recruited in Germany (n ¼ 1000), Italy (n ¼ 1000) and Spain (n ¼ 1000). To be eligible for the study, women had to have reported having heterosexual sexual intercourse in the preceding 3 months and not wanting to conceive in the near future or ever. Post-menopausal women, women believing themselves to be infertile and those using permanent contraception were excluded from the study. Recruitment was through an online panel (Toluna, https://uk. toluna. com). Panel membership is voluntary and demographic data and lifestyle information are provided. For the survey, quotas were set by age and region in order to identify a sample representative of each country and data were weighted to bring the sample in line with the known population profile.
This data descriptor reports on the upload to a public repository (GNPS) of the IQAMDB, IsoQuinoline and Annonaceous Metabolites Data Base, comprising 320 tandem mass spectra. This project originated from our in-house collection of isoquinolines. The diversity of compounds included in this database was further extended through the contribution of two additional laboratories involved in isoquinoline alkaloids research: University of Angers and University of Manaus. The generated MS/MS data were processed and annotated on an individual basis to promote their straightforward reuse by natural product chemists interested in either the description of new isoquinoline alkaloids or the dereplication of isoquinoline-containing samples. The interest of the current repertoire for dereplication purposes has been validated based on the molecular networking of the well-investigated plant model Annona montana against the IQAMDB-implemented GNPS.
In the quest for alternative industrial processes of natural product supplies, a few isoquinoline alkaloids of outstanding interest succumbed to biotechnological manufacturing, such as morphine  4  (and codeine as its biosynthetic intermediate) or noscapine  5. The very last years witnessed tremendous advances in the metabolic engineering of BIQ with the development of optimized yeast strains synthesizing a considerable amount of (S)-reticuline, a biosynthetic pillar in the TetraHydroIsoQuinoline (THIQ) series, but also a diversity of unprecedented BIQ derivatives  1. These advances in THIQ metabolite production guided Courdavault et al. to identify this family of compounds as holding "an eminent biosynthetic potential in the field of drug discovery"  6. Our continuous efforts towards the improvement of the molecular-networking pipeline efficiency through the upload of MS/MS data related with collections of structurally homogeneous natural products led us to implement two different databases today incorporated into the Global Natural Products Social Molecular Networking (GNPS) libraries  7.
A first contribution to these public repositories was dedicated to Monoterpene Indole Alkaloids 8 (so-called MIADB), implying an international consortium of eight different natural product laboratories that resulted in a collection of 172 initial entries, now reaching more than 220 compounds. Our second initiative in the field, the LDB (Lichen Data Base), garnered 241 structurally diverse lichen phenolic compounds based on a collaborative project with University of Rennes 1 and the Berlin Garden and Botanical Museum  9. We foresaw the possibility of building and deploying a third MS/MS database on the basis of the large diversity of isoquinoline alkaloids that have been isolated in Paris-Saclay  10. Described by Jussieu in 1789, the Annonaceae family comprises more than 120 genera and about 2100 species, all occurring in tropical and subtropical regions  11.
These works gratifyingly outlined the trend of Annonaceous alkaloids to clusterize in a scaffold-dependent manner. Some fragmentation patterns were even proposed by the same authors  24, 25  , leading to extend the annotation provided by this dereplication to untagged nodes based on the cursory examination of MS/MS spectra  20. We felt that our in-house collection of isoquinolines could set the ground for building a MS/MS database dedicated to Annonaceous metabolites. The core constitution of this Annonaceous and isoquinoline database was enlarged by inviting prominent natural products researchers in the field to share their collections with us. This collaborative work took advantage of additional Annonaceous isoquinolines included in the collections of Federal University of Amazonas and Amazonas State University (Manaus, Brazil).
To broaden the applicability of our database, this combined collection was further extended to structurally-related isoquinolines from non-Annonaceous plant sources through the incorporation of compounds obtained from University of Angers (France) which comprised isolates from Menispermaceous, Hernandiaceous, Lauraceous and Papaveraceous species  [26] [27] [28]. These contributions led us to constitute the largest MS/MS dataset of isoquinolines to date, namely the IQAMDB (IsoQuinolines and Annonaceous Metabolites DataBase) (https://gnps. ucsd. edu/ProteoSAFe/ gnpslibrary. jsp?library = IQAMDB) (Fig. 1  and Table  S1 )  29. This database should help pinpointing new chemical entities from isoquinoline-producing plants. We also hope that the upload of this database will be of interest to increase the reliability of the dereplication workflow in the frame of the very dynamic metabolic engineering efforts currently devoted to THIQ alkaloids.
Sample preparation. The different standard samples were dissolved in HPLC-MS grade methanol at 0. 5 mg/mL and placed into 1500 μL vials for analysis. For the alkaloidic extract, 1 g of dried and milled Annona montana Macfad. root bark was extracted using 50 mL of 0. 25 M H 2 SO 4 for one hour. The phase was alkalinized to a pH of 12 and counter-extracted three times using 35 mL of methylene chloride. The combined organic phases were evaporated in vacuo and dissolved in analytical grade methanol at a concentration of 0. 5 mg/mL for UPLC/ HRMS² analysis. Solvents were purchased from Sigma-Aldrich. Data acquisition. Samples were analyzed using an Agilent 6546 Accurate-Mass Q-TOF hyphenated with a 1290 Agilent Infinity II LC system. The chromatographic system was fitted with a Zorbax RRHD Eclipse Plus C18 column (2.
Database constitution. The analysis of all these substances resulted in 320 files with the standard Agilent. d format. The list of features detected in every sample was generated following the auto MS/MS data mining process implemented in MassHunter software on every single file. Within the list of detected features, the exact mass of the feature of interest was identified and the other features were filtered out. The MS/MS data related to the signal of interest were subsequently converted into a. mgf file using a tailored intensity threshold thanks to the dedicated "Export" option of the MassHunter software.
Molecular networking parameters (using IQAMDB standards as an input). Every single MS/MS spectrum related to the IQAMDB standards was curated as indicated in the Database constitution section. A molecular network was then created using all the. mgf files as an input, using the online molecular networking workflow (version release_28. 2) at GNPS 7 (http://gnps. ucsd. edu) with a parent mass tolerance of 0. 02 Da and a MS/MS fragment ion tolerance of 0. 02 Da. The data were not clustered with MS-Cluster. A network was then created where edges were filtered to have a cosine score above 0. 6 and more than 6 matched peaks. Further edges between two nodes were kept in the network if and only if each of the nodes appeared in each other's respective top 10 most similar nodes. The spectra in the network were then searched against GNPS spectral libraries.
Feature-based molecular networking parameters (dereplication of A. montana). The MS2 data files related to the alkaloidic extract of Annona montana were converted from the. d (Agilent) standard data-format to. mzXML format using the MSConvert software, part of the ProteoWizard package  31. The. mzXML file was further processed using MZmine 2 v53  32. Mass detections were performed using a noise level threshold at 2E3 in MS1 and at 1. 5E1 in MS2. The ADAP chromatogram builder used a minimum group size of scans of 2, a group intensity threshold of 2E3, a minimum highest intensity of 2E3 and a m/z tolerance of 10 ppm  33. The chromatogram deconvolution used the Local Minimum Search algorithm with the following settings: chromatographic threshold = 1%, search minimum in RT range (min) = 0. 05, minimum relative height = 2%, minimum absolute height = 1E3, min ratio of peak top/edge = 0.
Further edges between two nodes were maintained only if each of the nodes appeared in each other's respective top 10 most similar nodes. The spectra in the network were then searched against GNPS spectral libraries. Matches between network spectra and library spectra were required to have a cosine score above 0. 6 and at least 6 matched peaks. The molecular networking data were analyzed and visualized using Cytoscape (ver. 3. 6. 0)  30. The obtained molecular network can be accessed at: https://gnps. ucsd. edu/ProteoSAFe/status. jsp?task = 3ff5f1048c7948ff96627438ac905acd.
Data Records Data reported in this article have been uploaded to the GNPS platform. Each MS² spectrum of the 320 compounds is assigned an individual accession number on the GNPS. The. mgf files were deposited and are publicly available at the MassIVE repository (MSV000088909) (https://doi. org/10. 25345/C55D8NG3T)  34. The spectral collection is available for download from the library webpage of the GNPS (https://gnps. ucsd. edu/ProteoSAFe/libraries. jsp)  29.
Retained strategies for IQAMDB validation. The validation of the IQAMDB repertoire was achieved following two distinct strategies. At first, the topology of the molecular network obtained using the IQAMDB as an input was inspected to assess whether the uploaded MS/MS data could outline structural similarities between the standards included in the database, as a first indicator of the quality of IQAMDB spectrometric data. Then, the dereplication efficiency of the IQAMDB-implemented GNPS libraries was estimated by annotating the molecular network obtained from the alkaloidic extract of the thoroughly studied Annona montana Macfad. Topology of the molecular network obtained using the IQAMDB as an input. The molecular network generated using the tandem mass spectra of the IQAMDB as an input is disclosed in Fig.