dataesr/scientific-paragraphs-categorization huggingface dataset:
At first, we generated a structural model of CSE based on the crystal structure of CSE (PDB code: 2 NMP). Our minimized molecular model mainly differs from the crystal structure in the following points: (1) since the quaternary structure of the enzyme consists of a dimer of dimer  36  , we choose to work with a minimalist model constituted of a single dimer comprising the A and B subunits; (2) hydrogen atoms were added such as the pyridine moiety from the cofactor and the imine bond between the Nε-lysine (Lys212) and the C4′ atom of PLP are accurately protonated; (3) the length of the aforementioned imine bond is of 1. 30 Å in our model while it exhibits an unusual length of 1. 96 Å in the crystal structure (PDB code: 2 NMP); (4) last, Asn161 is no longer in H-bond contact with the O3' atom of PLP.
S6A ). Additionally, the distal part of the substrate principally initiates hydrogen bond contacts at the entrance of the substrate channel with the side chains of *Arg62, *Asn241, Tyr114 that was postulated to act as a base for deprotonating the substrate  49  , Glu339 that has been proposed to govern the specificity of CSE-catalyzed reactions  50, 51  , and the backbone of Thr355. Last, Asn161 and Thr355 provide hydrogen-bond interactions with the proximal α-carboxyl group of cystathionine at the bottom of the substrate binding site, as does Arg375 according to previous docking experiments performed with yeast CSE  49  (Fig. S6B ). Interestingly, the H-bond contacts implicating Asn161 and Arg375 might be preserved along the course of CSE-catalyzed reactions as the carboxylate of an aminoacrylate bound to CSE (PDB code: 6NBA) forms hydrogen-bonding interactions with both amino acid residues  32.
This would allow the Schiff linkage to adopt a single-bond resonance form and to easily rotate around the C4′-C4(pyridine) axis, thus creating a more electrophilic carbon at the C4′ position and facilitating the nucleophilic attack of the amine group of the substrate (species C). Second, the O3′ atom could intervene in the indirect deprotonation of the substrate as suggested by QM/MM calculations during the degradation of l-methionine by methionine γ-lyase from Pseudomonas putida  55. In this case, the O3′ atom contributes to the water-assisted deprotonation of the substrate, which has been found more favourable and less energetic than the direct deprotonation of l-methionine by the O3′ atom to generate the nucleophilic species prior to gem diamine formation. A water molecule located 4. 3 Å away from the O3′ atom in the resting state of CSE (PDB code: 2NMP) could accomplish this task admitting that such a mechanism is followed by CSE during the α,γ-elimination of cystathionine.
plantarum CGL (PDB code: 6LE4)  53  and in human CSE harbouring an aminoacrylate intermediate (PDB code: 6NBA)  32. Last, the H-bond could also modulate the electrophilic character of the C4′ atom. Thus, while the protonation state of N1-pyridine determines the absolute acidity of the Cα and C4′ of aldimines and ketimines, the protonation state of imine and O3' modulates the relative acidities of the Cα and C4′  58, 59. Accordingly, the snapshot captured at 50 ns during MD simulations (Fig. 5B  and D ) could represent an enzyme conformation needed for promoting catalysis and particularly for lowering the activation energy of the transition state leading to gem diamine intermediate formation.
Prediction of D-penicillamine binding sites and docking of the ligand. Next, we performed computational studies to identify putative ligand binding sites within CSE and further carry out similar studies on the ternary complex CSE-substrate-ligand. The prediction of the ligand binding sites was performed with the Galaxy site program using the crystal structure of CSE (PDB code: 2NMP, A and B chains) and with the Cavity search program from Biovia Discovery Studio (DS) 2021 using our minimized molecular model as input. Molecular docking was performed with CDOCKER software implemented in DS. Best binding site were retained based on docking score (CDOCKER interaction energy and CDOCKER energy scores). Thus, amongst the seventy-one putative ligand-binding sites, eighteen of them were selected for docking studies based on their size as well as their location on the enzyme.
6  and 7A ). Last, docked D-pen to site 33 (CDOCKER energy and CDOCKER interaction energy of -35. 7 kcal/mol and -27. 4 kcal/mol, respectively) intervenes into H-bond formation with the backbone of Gln123 and is in an H-bond interacting radius with the side chains of Gnl123 and Glu127 (Fig. S13A ). In addition, D-pen establishes C-H…O connections with the side chain of *Phe238 and Gln123, van der Waals contact with *Leu239, O•••S and C-H…S interactions with Glu127. Surprisingly, even though sites 33 and 42 have already been identified in the literature, they have been designated as putative activator binding sites  28, 61. Thus, residues surrounding site 42 have been proposed to establish electrostatic interactions with the phenoxy part of isoxsuprine, a presumed allosteric activator of CSE solely based on high-throughput virtual screening performed with the protein structure in complex with propargylglycine (PDB code: 3COG)  28.
First, the effect of D-penicillamine on the activity of CSE was determined from a reaction mixture containing 1 mM cysteine, 0. 4 mM lead acetate and varying concentration of D-penicillamine (up to 100 mM) in 200 mM HEPES at pH 7. 4. After 3 min of preincubation of the assay mixture at 37 °C, the reaction was initiated by adding 40 μg of CSE. Then, the formation of lead sulfide resulting from the reactivity of H 2 S with lead acetate was continuously monitored at 390 nm. The half inhibitory concentration (IC 50 ) value was obtained by plotting the relative activity of CSE (A, in per cent) as a function of the concentration of D-pen and by fitting the data with Eq. (  4 ), where ∆A is the maximal effect of D-pen on the activity of CSE and n is the Hillslope that characterizes the slope of the curve at its midpoint.
(  6 ), whit F 0 the minimal relative fluorescence at saturating D-pen concentration, ∆F max the maximal relative decrease in fluoresence emission provoked by D-pen binding to CSE, and n the Hill coefficient that leasures the potential cooperativity in ligand binding process. Molecular docking and dynamics studies. The crystal structure of the PLP bound human CSE tetrameric complex was downloaded from the Protein Data Bank (PDB ID: 2NMP, https:// www. pdb. org). A dimeric structure of CSE formed by chains A and B was prepared using the Prepare Protein module in Biovia Discovery Studio (DS) 2016 with the default parameters and the CHARMM force field. Briefly, all crystallographic water molecules, except HOH 512, were removed. Bond orders were assigned, hydrogen and missing atoms were added.
The protonation states on protein and PLP were adjusted at pH 7. 4. The imine bond between Lys212 and C4' atom of PLP was created using the Build and Edit Protein tool of DS. Finally, the protein/PLP complex 3D structure was minimized using the Adopted Basis Newton-Raphson (ABNR) algorithm. The 3D-coordinates of l-( +)-cystathionine and D-penicillamine were generated using the Prepare Ligand module in DS with ionization states calculated at pH 7. 4. Random conformations of each ligand (8 for D-penicillamin and 26 for cystathionine) were generated for docking experiments using the BEST algorithm  38  to improve the coverage of the conformational space. Docking studies were performed using CDOCKER  39  implemented in DS 2016 and all parameters were kept at their default values. Potential binding sites in the CSE protein structure were determined using the receptor cavities tool of DS and the fpocket application  40  within the Galaxy server (https:// chemi nform atics.
usega laxy. eu/). Pose clustering, based on the RMSD values, was performed using the RMSD tool of DS. Best poses within each cluster, based on the CDOCKER Interaction Energy and CDOCKER Energy scores, were further refined through the In Situ Ligand Minimization protocol of DS. Following this, the binding mode of compounds was thoroughly examined using the Analysis Ligand Poses module of DS. To assess the structural stability of the l-(+)-cystathionine-and D-penicillamine-bound CSE, 50 ns of molecular dynamics simulations were run starting from best docking models using the CHARMM36m force field and the NAMD protocol  41  implemented in DS 2021. Protein-ligand complexes were solvated in an orthorhombic box using a TIP3P water model. Periodic boundary conditions were applied with a minimum distance of 7 Å from periodic boundary and Na+ Cl-counter ions were added to neutralize the system.
Patient selection criteria It was a multicentre, open, uncontrolled and non-randomized study designed to evaluate the added value au 18F-FDOPA to the conventional management of high-grade glioma patients. The study (N° ID-RCB: 2015-A00520-4) was conducted prospectively in 5 French University Hospitals from January 2016 to February 2019 under the leadership of the Centre Antoine Lacassagne. Each case was discussed during each institution weekly Multidisciplinary Neuro-Oncology Board (MNOB) meetings. The study was approved by the Ethic Committee, the Agence Nationale de Sécurité du Médicament (ANSM) and registered (https://clinicaltrials. gov/ct2/show/NCT02631655) in 2015. Inclusion criteria were (i) histopathologically proven high-grade gliomas (WHO grade III and IV); (ii) age more than 18 years; (iii) signed informed consent; (iv) patients referred to the multidisciplinary neurooncology board (MNOB) of each institution in the setting of decision making in the follow-up after initial standard of care treatment (surgery and radio-chemotherapy) and (v) patients for whom MRI ndings were not leading to a high con dence level in the decision to be made by the MNOB.
Objectives of the study The primary objective was to measure the changes in diagnosis and management proposed by the MNOB induced when taking into account the 18F-FDOPA PET information by comparing diagnostic proposals and management proposals 1 and 2. The secondary objectives were: (i) to measure the difference in the con dence of the decisions when diagnostic and management were not changed by comparing the con dence levels in those cases and (ii) to evaluate the diagnostic performances of 18F-FDOPA in terms of sensitivity, speci city and accuracy for the diagnosis of progression or recurrence when compared to pathology when available or to the radiological and clinical follow-up. The radiological and clinical data used as diagnostic reference were those collected during the systematic 3 months visit after the MNOB decision.
Statistical analysis The required number of patient cases to be evaluated was calculated prior to the start of the study to be 110 (taking into account 10% of wrongly included patients, lost to follow-up or withdrawn from the study). Data entry and management were performed on the capture system (Ennov Clinical). Categorical data are shown as counts and percentages and continuous variables as means with standard deviations. Comparisons were evaluated using χ 2 test or Fisher's exact test for categorical data and Student's test or Wilcoxon's test for continuous variables. Statistical analyses were performed with SAS software version 9. 4 (SAS Institute Inc) and R 3. 6. 0 (R Foundation) on Windows® and the caret and DTComPair packages. Results were considered statistically signi cant at a p value of less than 0.
Flow cytometry Single-cell suspension of hiPSC was collected after chemical dissociation with accutase (Invitrogen, United States), centrifuged at 900 rpm for 5 min, and resuspended in 2% FBS (Sigma, United States) in cold PBS. Cells were stained with fluorescent dye-conjugated antibodies (listed in Supplementary Table  S3 ) for 30 min on ice and protected from light. Cells were washed in cold PBS before being assessed by a MACSquant analyzer (Miltenyi Biotec, Germany). Data were analyzed with FlowJo Software (BD Biosciences, United States).
Multiplex fluorescence in situ hybridization (m-FISH) karyotype analysis Cells were blocked in metaphase with colchicine (Eurobio, France) for 90 min, warmed with a hypotonic solution, and fixed with a Carnoy fixative. A M-FISH 24Xcite probe (MetaSystems, Germany) and ProLong Gold Antifade Mountant with DAPI (ThermoFisher Scientific, United States) were used for m-FISH staining. Seventy metaphases were acquired with Metafer MetaSystems software coupled to an AxioImager Z2 (Zeiss, Germany) microscope equipped with a camera cool cube and ×10 and ×63 objectives. Images were analyzed with Isis software (MetaSystems).
Periodic Acid Schiff (PAS) staining PAS staining was performed with the PAS Staining Kit (Sigma-Aldrich, United States) following the manufacturer's instructions. Briefly, cells were fixed with 4% paraformaldehyde for 10 min at room temperature. After two washes in PBS, skMt were treated with Periodic Acid Solution for 5 min at room temperature. After three washes in tap water, cells were treated with Schiff's reagent for 15 min at room temperature. Finally, after four washes in tap water, staining was visualized using an EVOS XL Core microscope (Invitrogen, United States). Images were processed and analyzed using FIJI custom-made scripts  (Schindelin et al. , 2012). First, colors were split and only the green channel was kept as it was the most contrasted one. Then, images were manually thresholded into binary images where PAS signal was in black and background in white.
Measurement of glycogen content Glycogen content was measured using the Glycogen-Glo assay (Promega, United States) following the manufacturer's instructions. Briefly, skMt were lysed using an HCl acidic solution to aid in cell disruption, inactivation of endogenous enzymes and degradation of endogenous NADH. Glycogen was then digested into glucose by incubation with glucoamylase enzyme for 1 h at room temperature. The resulting glucose was then measured using glucose dehydrogenase in conjunction with a bioluminescent NADH detection reagent incubated for 1 h 30 min at room temperature. The result was a light signal proportional to the starting glycogen concentration in skMt. Luminescence was read using a CLARIOstar ® microplate reader (BMG Labtech, Germany). Raw data related to glycogen content were normalized on the number of viable cells measured by luminescence using CellTiter-Glo assay (Promega, United States).
Acknowledgments The authors thank the platform of AAV vectors production of the immunology and liver gene transfer team at  Genethon. We are grateful to the  Imaging and Cytometry core facility of Genethon (ImCy)  for technical support. The ImCy facility belongs to  France Bio Imaging  national infrastructure. We thank  Marc Peschanski  ( I-Stem ) for helpful discussions. The authors are Genopole's members, first french biocluster dedicated to genetic, biotechnologies, and biotherapies. We are grateful to  GIP Genopole (Evry)  for the purchase of the equipments.
Like DLS and NFCM, NTA exploits the light scattered by nanoparticles upon illumination with a laser, but the trajectories of single nanoparticles are followed, making it possible to determine their hydrodynamic diameter (Dh), which is the diameter of a hard, perfect sphere with a zero surface charge that would diffuse at the same speed as the measured particle (for simplicity, we will use size to indicate Dh when discussing measurements provided by NTA). The ZetaView (Particle Metrix, Germany) and NanoSight (Malvern, UK) are two devices that rely on NTA commonly used in the EV field. Although they are based on the same principle, the ZetaView and NanoSight present important differences in the composition of their hardware and software  (Bachurski et al. 2019). For example, with the NanoSight instrument, a flux is generally applied to the sample during acquisition, whereas the acquisition is recorded on a static sample with the ZetaView.
In accordance with the manufacturer's specifications, a relative threshold of 3. 8 was applied for detection. The removal of macroparticles was enabled using a minimum radius of 10 and a minimum number of hot pixels of 80, as well as drift compensation. Concerning the tracking settings, a maximum of two jumps was tolerated for a minimal length track of 10 frames. The doublet detector (qvir software version 2. 5. 2. 6196) was used for all measurements. Size distributions were obtained after the application of a mobile mean with a period of 3 on histograms with classes of 5 nm. For linearity measurements, polystyrene beads (Polystyrene Nanosphere Suspension Series 3000, ThermoFisher) of various sizes were diluted in water after a short sonication. Bead concentrations were calculated following the indications of the Nanosphere supplier provided in the technical guide.
The NanoSight phage detection threshold was therefore between 30 and 60 nm. The concentrations obtained were in relatively good agreement with the EPI counts, with values that were generally 1-to-3-fold lower for all phages (Fig. 3B ). The ZetaView also detected most of the phages except two: ΦX174, as the NanoSight, as well as SPP1. This is surprising, as the published diameter of the SPP1 virion, 61 nm, is similar to that of λ and T7 phages (Table  2 ), which were correctly detected. Of note, SPP1 particles create a visible signal that is nonetheless too low to be detected by the ZetaView software with the parameters used in this study, indicating that SPP1 virions are just below the detection threshold. This may result either from a slightly smaller size of the SPP1 virions, as suggested by our TEM observations indicating a diameter of approximately 57 nm (Table  3 ), from a lower refractive index of SPP1 virions relative to other phages, or to smaller surface charge (which results in a smaller hydrodynamic diameter).
We therefore considered that the detection threshold of the ZetaView is slightly over 60 nm for phages. For phages with a capsid larger than 60 nm (T4, T5, ΦCrAss001 and PRD1), the ZetaView concentrations were in very good agreement with the EPI counts (Fig. 3B ). The Videodrop correctly detected only the largest phage, T4. T5 and ΦCrAss001 virions created visible spots, but the intensity of the signal was too low to be detected by the software, indicating that the particle signal is just below the detection threshold of the device. Given that the size of the T5 and ΦCrAss001 capsid is close to 90 nm (Table  2 ), this suggests that the Videodrop detection threshold is slightly over 90 nm for phages. In conclusion, the NanoSight and ZetaView correctly enumerated phage particles larger than 50 nm and 60 nm, respectively, consistent with previous studies on synthetic nanoparticles  (Bachurski et al.
Statistical analysis As a first step, we described participants' (1) aspects implicated in parental consent (i. e. , autonomous decision-making capacity assessed by the health professional, knowledge of parents or guardians about the intention to participate before signing the informed consent form, and parent's or guardian's signature on the informed consent form), (2) sociodemographic characteristics (i. e. , gender identity, skin color/race -selfreported and based on the categories 'white,' 'black,' 'brown,' 'yellow,' and 'indigenous' used by the Demographic Census of the Brazilian Institute of Geography and Statistics (IBGE) -, and education), and (3) vulnerability to HIV (i. e. , transactional sex, use of illicit drugs, except marijuana, and sexual violence in life). Data obtained from eligibility and consent forms were used to describe aspects related to consent.
Data from behavioral questionnaire were used to describe participants' profile. We considered data on participants aged 15e17 years who enrolled in the study between February 2019 and September 2022. To describe differences across study sites, we used chi-square test, and when differences in the distributions were observed, the adjusted standardized residual (Zres) was used to identify significant differences (AE 1. 96). As a second step, to analyze whether court decisions supporting adolescents' autonomy to consent independently were associated with higher inclusion of vulnerable adolescents in the research, an HIV vulnerability score was created by combining the sum of the three variables (i. e. , transactional sex, illicit drug use, or sexual violence); the presence of two or more variables was considered a situation of greater vulnerability.
Acknowledgment of the risks associated with mandatory parental consent by the ERCs was not accompanied by the adoption of measures to prevent the systematic exclusion of individuals in a situation of greater vulnerability. In line with previous studies, our findings indicated that the different requirements for parental consent impacted young people's access to the study (and consequently to PrEP). The chances of including vulnerable adolescents increased as restrictions decreased, being three times higher in the city where the blanket waiver was in place. To fulfill the ethical principle of justice, achieve universal access to health services, and realize the rights to health and nondiscrimination, we need to reach the most vulnerable. Moreover, doing this in a research context is a prerequisite to evidence-based services for these populations.
Acknowledgments The authors are grateful to the adolescents for participating in this study, to their parents and guardians for signing consent forms when necessary, to the health professionals and peer educators for their work in providing care and helping create demand for prevention services in PrEP1519 study sites, and to the institutions that contributed to the development of the study: (i) Salvador: the  Bahia State and Salvador Municipal Health Departments , the  Diversity Center of the Bahia State Justice and Human Rights Department , and the  Public Prosecution Service of the State of Bahia ; (ii)  São Paulo : the  STI/AIDS Coordination  and the  Henrique de Souza Filho Testing and Counseling Center , both linked to the  São Paulo Municipal Health Department , the  Extension Service for HIV/AIDS Patient Care of the Infectious Diseases Department of the Clinic Hospital, Faculty of Medicine, University of São Paulo ,  NGOs CASA 1  and  Periphery Identity , and the  Office of the Prosecutor for Children and Youth of the Public Prosecution Service of the State of São Paulo; (iii)   Belo Horizonte , the  Minas Gerais State  and  Belo Horizonte Municipal Health Departments , the  Youth Center of the Belo Horizonte Municipality , and the  Public Prosecution Service of the State of Minas Gerais.
To determine the half maximal inhibitory concentration (IC50) of CFS4, several concentrations were tested (0. 0005, 0. 005, 0. 05, 0. 1, 0. 187, 0. 375, 0. 75, 1. 5, and 3 g/L); the results are To determine the half maximal inhibitory concentration (IC50) of CFS4, several concentrations were tested (0. 0005, 0. 005, 0. 05, 0. 1, 0. 187, 0. 375, 0. 75, 1. 5, and 3 g/L); the results are presented on Figure  5. Based on these dose-response curves, absolutes of IC50 calculated with the GraphPad Prism 8 software were 0. 1418 g/L for AFB1 and 0. 5006 g/L for AFB2. presented on Figure  5. Based on these dose-response curves, absolutes of IC50 calculated with the GraphPad Prism 8 software were 0. 1418 g/L for AFB1 and 0. 5006 g/L for AFB2.
Transcriptomic Response of A. flavus to CFS4 Exposure To study the impact of CFS4 (1. 5 g/L) on A. flavus at the transcriptional level, a genome-wide transcriptomic analysis by microarray was performed. A set of 8544 probes (corresponding to 8544 genes) was identified as significantly differentially expressed (FDR < 5%) between the control and the CFS4 exposure condition. Principal component analysis (PCA) performed on the log2FC values of the dataset revealed a clear separation of the control and CFS4 condition, along with the first component, which explained 83. 6% of the total variance (Figure  6A ). Hierarchical clustering of individual expression values was performed on 5198 significant features for the CFS4-CTRL comparison, based on the FDR method, with a p-value and fold change (FC) threshold respectively set to 0.