dataesr/scientific-paragraphs-categorization huggingface dataset:
Acknowledgements We are highly grateful to the  Vandoeuvre-Lès Nancy Centre de Médecine Préventive  staff, and to  Dr Sophie Visvikis-Siest  ( INSERM U1122 ) who managed the STANISLAS Cohort for the first three visits. The authors deeply thank the  Staff of the Clinical Investigation Center  and other personnel involved in the Stanislas Cohort management: Biostatisticians: Fay R, Lamiral Z,  Machu JL. Computer  scientists:  Boucenna N, Gallina-Müller C, Maclot PL, Sas T. Coinvestigators: Chau K, Di Patrizio P, Dobre D, Gonthier D, Huttin O, Malingrey L, Mauffrey V , Olivier A, Poyeton T, Steyer E, Watfa G. Datamanagers: Cimon P, Eby E, Merckle L. Data entry operators:  Batsh M, Blanger O, Bottelin C, Haskour N, Jacquet V, Przybylski MC, Saribekyan Y, Thomas H, Vallée M. Echocardiographists, echographists: Ben Sassi M, Cario S, Camara Y, Coiro S, Frikha Z, Kearney-Schwartz A, Selton-Suty C, Watfa G.
PARTICIPANTS Recruitment and screening Participants were recruited continuously by multiple routes, for example, web pages, social media, newspapers and registries (local databases or civil registration numbers). Potential adult participants were prescreened by phone and answered questions on behalf of their child(ren). If still eligible and interested after prescreening, they received written information and were invited to an information meeting. After the information meeting, an informed consent form and a general data protection regulation form were signed by the adult participant, and for children by the parents or person(s) having custody and the site-PI or delegated staff. Thereafter, the screening visit was scheduled. Participants were screened in the fasting state, where all inclusion and exclusion criteria were assessed.
Data collection and outcomes Including information meeting, screening, counselling sessions and CIDs, the trial consists of a minimum of 10 or 6 visits for adults and children, respectively. Data are collected according to standard operation procedures (SOPs) and table  4  shows activities/data collection at each visit. Most data will be collected at months 0, 2, 6 and 12, where participants have fasted for a minimum of Open access 10 hours and avoided intensive physical exercise, coffee and smoking for 12 hours prior to the CIDs.
Anthropometry Height is measured to the nearest 0. 5 cm using a stadiometer at screening and for children at all CIDs. For adults, BMI is calculated as body weight (kg)/height 2 (m 2 ). For children, the WHO AnthroPlus software (www. who. int/ tools/growth-reference-data-for-5to19-years/application-tools) is applied to calculate BMI-for-age percentile and z-score. Waist and hip circumferences are measured two times with a non-elastic tape measure on the skin to the nearest 0. 5 cm, and the average is calculated. Waist circumference is measured halfway between the lowest rib and iliac crest during exhalation. Hip circumference is measured as the largest circumference in the area around the buttock. Dual-energy X-ray absorptiometry (DXA) scans are performed in underwear to assess body composition, including fat percentage, fat mass and fatfree mass.
27 28 REDCap is a secure, web-based software platform designed to support data capture. Source data from DXA scans and analysis of biological material are registered on the device or related hardware, whereas the source data from dietary records (handwritten on paper) will be entered into a national dietary software programme for analysis. The sponsor/investigator will provide direct access to source data/documents for inspection. Results will be published in international peer-reviewed scientific journals regardless of whether the findings are positive, negative or inconclusive.
Of these nine studies, only two studies investigated effects of both foods and drinks  32 33  and five of the nine studies investigated effects of a single S&SE. Furthermore, only two studies  34 35  had a duration of a minimum of 6 months, but none of these had the same weight loss and weight maintenance design as the current RCT. Thus, studies investigating the effect of S&SEs, compared with sugar, for weight loss maintenance are lacking. Other strengths are that the trial is conducted as a multicentre trial covering four European countries with both adults and children included. Furthermore, data will cover a broad range of measurements related to health (body weight Open access management, risk factors for CVD, T2D, etc) and safety (microbiology, allergy, AEs), appetite and food preferences.
These will be measured at baseline, after a 2-month WL (adults) or 2-month weight stability (children) period, and after a 10-month intervention period. A trial limitation is that the number of included children was lower than initially planned, but this will not affect the two primary outcomes. Another limitation is that data related to energy and nutrient intakes (food records) are only collected at baseline and at months 12. However, urinary S&SE biomarkers collected at baseline, month 6 and month 12 will indicate if compliance decreases before month 12.
Ethics and dissemination The trial protocol has been approved by the following national ethical committees; The research H-19040679, The medical The SWEET EU project was initiated by JCGH, AR and JAH. The protocol for the SWEET intervention trial was written by LK, AR and YM, with contribution from EEB and JAM. AR, YM, EEB and JAM are principal investigators (PI) at the four intervention sites, where LK, SSHA, SN-C, KR and TA are investigators. The trial is funded by the  Horizon2020 program : Sweeteners and sweetness enhancers: Impact on health, obesity, safety and sustainability (acronym: SWEET, grant # 774293 ) and funding covers salary for project personal, supplies, remuneration, and dissemination of results. The amount is deposited in a project account subject to audits/public revision.
The search was limited to papers in English language with no restriction of publication date. Articles including human intervention studies (randomized controlled trials, controlled clinical trials, acute, short-term, or long-term studies) or observational studies (cohort, case-control, cross-sectional studies) were taken into consideration. Search results were imported into EndNote X9 (Thomson Reuters, New York, NY, USA). After removal of duplicates, a primary selection was conducted in Rayyan (Rayyan Systems Inc. , Cambridge, MA, USA) based on the relevance of abstract and title. The exclusion criteria were as follows: effect on physiology or clinical endpoint, effect on drug metabolism, food analysis, in vitro studies, animal studies, irrelevant foods, children over 18 years old, fruit and vegetable juice and drink intake, conference abstracts, short communications, editorials, and comments.
In this step, Google Scholar was also used as a search platform, in addition to the above three databases. Additionally, the compounds were searched manually in the online databases HMDB (https://hmdb. ca/, accessed on 15 March 2021), Phenol-Explorer 3. 6 (http://phenol-explorer. eu/, accessed on 15 March 2021), and PubChem (https://pubchem. ncbi. nlm. nih. gov/, accessed on 15 March 2021) to determine all the possible dietary or metabolic origins of the candidate BFVI.
Evaluation of the Validation of Candidate BFVI The secondary search was also used to obtain additional information for assessing the level of validation for biomarkers. A set of validation criteria proposed by Dragsted et al. [19]  was applied to evaluate the level of validation of candidate biomarkers. The validation scheme is based on eight questions that encompass biological and chemical aspects: Q1: Is the marker compound plausible as a specific biomarker for the food or food group (chemical/biological plausibility)? Q2: Is there a dose-response relationship at relevant intake levels of the targeted food (quantitative aspect)? Q3: Is the biomarker kinetics described adequately to make a wise choice of sample type, frequency, and time window (time-response)? Q4: Has the marker been shown to be robust after intake of complex meals reflecting dietary habits of the targeted population (robustness)? Q5: Has the marker been shown to compare well with other markers or questionnaire data for the same food/food group (reliability)? Q6: Is the marker chemically and biologically stable during biospecimen collection and storage, making measurements reliable and feasible (stability)? Q7: Are analytical variability (CV%), accuracy, sensitivity, and specificity known to be adequate for at least one reported analytical method (analytical performance)? Q8: Has the analysis been successfully reproduced in another laboratory (reproducibility)?.
Results A total number of 3752 papers were retrieved from three databases, while the number of 402 from Scopus was the result after removal of duplicates from PubMed. After screening based on title and abstract, 49 papers were selected for full text reading. A total of 26 additional papers were removed, including 2 conference abstracts, 8 manuscripts regarding adult subjects, and 16 investigating pesticide contaminants. Through full text reading, 5 more papers were identified from the reference lists of these included articles. Subsequently, a total of 28 papers qualified for inclusion in the present review. Six of these papers investigated potential BFVI from skin samples, 20 from blood and 5 from urine, including 1 with both blood and urine samples and another 2 with both blood and skin samples.
[23]  aimed at verifying or assisting FV intake assessment instruments by using potential biomarkers on the basis of hypothesis-driven targeted metabolomic approaches. Lau et al. [23]  used an untargeted high-throughput nuclear magnetic resonance spectroscopy to identify novel biomarkers. There were barely any data in the literature on potential BFVI for specific fruits or vegetables consumed at a young age. Only a few intervention studies investigated associations between wild blueberry, amaranth, cowpea, and Momordica cochinchinensis consumption and metabolites in children and adolescents, with 1 exception (papaya) conducted in a cross-sectional study. In total, 18 different potential BFVI were investigated in children and adolescents. The number of potential BFVI measured per study varied from 1 to 6.
2. 2. Literature Search for Biomarkers of Fruit and Vegetables Intake (BFVI) in Children and Adolescents An extensive literature search was carried out in three databases (PubMed, Scopus, and Web of Science) in January 2021 and updated in August 2021. Keywords included a combination of fruits and vegetables and a group of search terms (fruit* OR vegetable* OR citrus OR berry OR berries OR apple* OR grape* OR pear* OR orange* OR banana* OR mango* OR pineapple* OR tomato* OR potato* OR onion* OR pea* OR leek* OR spinach* OR lettuce* OR endive* OR asparagus* OR kale OR brassica OR cabbage* OR "cruciferous vegetable*") AND (urine OR urinary OR plasma OR serum* OR excretion* OR blood OR skin OR saliva) AND (biomarker* OR marker* OR metabolite* OR biokinetics OR biotransformation OR bioavailability OR ADME OR metabolom*) AND (child OR youth OR juvenile* OR preschool OR boy* OR girl* OR teenage* OR children OR childhood OR adolescence OR infant* OR infancy OR adolescent*).
PacL1 is required for resistance to zinc intoxication in M. tuberculosis PacL1 is encoded together with CtpC and contains a domain of unknown function (DUF), namely DUF1490 (Fig. 1a , http://pfam. xfam. org/family/PF07371). In silico analyses predict that PacL1, like most DUF1490-containing proteins, contains a transmembrane (TM) domain, a cytoplasmic part with Glu/Ala repeats, an intrinsically disordered region (IDR) of variable length, and a C-terminal metal-binding motif (MBM) (Fig. 1a ). Moreover, PacL1 shows some homology to canonical chaperones, such as mycobacterial GroEL1 (Supplementary Fig. 1a ). DUF1490-containing proteins form a family of previously undescribed proteins that are present exclusively in Actinobacteria. In M. tuberculosis, the P 1B -ATPases CtpG and CtpV are also encoded with DUF1490-containing proteins, namely Rv1993c (PacL2) and Rv0968 (PacL3), respectively (Supplementary Fig.
PacL1 and CtpC cluster into membrane foci independent of flotillin Next, we investigated the sub-cellular localization of CtpC and PacL1. As expected, recombinant His 6 -or mVenus-tagged CtpC localized exclusively to the membrane fraction in M. smegmatis Δ2 coexpressing PacL1 (Fig. 2a  and Supplementary Fig. 3a ). Recombinant FLAG-or mTurquoise-tagged PacL1 also localized mostly to the membrane fraction in M. smegmatis Δ2 co-expressing CtpC (Fig. 2a  and Supplementary Fig. 3a ). Importantly, deletion of the TM domain in PacL1 (i. e. , Leu 7 -Glu  25  , resulting in "PacL1(ΔTM)") impaired this membrane localization of PacL1 (Fig. 2b ) and complementation of the M. tuberculosis ΔpacL1 mutant with this variant did not restore resistance to zinc excess (Fig. 2c ). These data suggest that plasma membrane association is required for PacL1 function.
i M. tuberculosis H37Rv (wild-type, WT, left panel), or a M. tuberculosis mutant deleted in Rv1488 (ΔRv1488) were cultivated in complete 7H9 medium in the absence (Control, black lines) or presence of 100 μM or 250 μM ZnSO 4 for 15 days. Bacterial growth was quantified by turbidity measurement (reported in McFarland's units). Data show mean ± s. d of a biological replicate (n = 3), and are representative of 2 independent experiments. In the right panel, the dotted line reproduces data for WT in the left panel to show that there is no difference between the WT and the ΔRv1488 mutant in sensitivity to zinc at 250 μM. j Formaldehyde-fixed M. tuberculosis mutant ΔRv1488 expressing mTurquoise-and mVenus-tagged PacL1 and CtpC, respectively, was examined using an Eclipse TI-E/B wide field epifluorescence microscope.
Zinc quantification in mycobacteria M. smegmatis was cultured in 7H9 medium containing Tween-80 but without ADC. When OD 600 reached 0. 5, ZnSO 4 (100 µM) was added or not (control) to the cultures. After 1 h incubation at 37 °C, bacteria were washed 2 times in 7H9 medium. FluoZin-3 (FluoZin™-3, AM, cell permeant, Thermo Fisher) was added at 1 mM, and cultures were incubated for 1 h at 37 °C. Samples were washed, recovered in PBS and observed by fluorescence-activated cell sorting (FACS); data were analysis using FlowJo (v10) software.
FACS analysis of fluorescent reporters M. smegmatis mc²155 cultures were inoculated in complete 7H9 medium at OD 600 0. 03 with different concentrations of metals (ZnSO 4 , MnSO 4 , CuSO 4 ). After incubation overnight at 37 °C bacteria were collected and observed by FACS; data were analysis using FlowJo (v10) software. The mCherry signal was used as basal level of expression. FACS was performed using an LSR Fortessa (BD Biosciences) flow cytometer. Gating strategy is displayed in Supplementary Fig. 14.
Fluorescence microscopy Mycobacterial cultures expressing fluorescent plasmids were applied as 0. 6 µL drops to the surface of a layer of 1% agarose in growth medium, as we described previously  72. The cells were imaged at 30 °C using an Eclipse TI-E/B wide field epifluorescence microscope with a phase contrast objective (CFI Plan APO LBDA 100X oil NA1. 45) and a Semrock filter YFP (Ex: 500BP24; DM: 520; Em: 542BP27), CFP (Ex: 438BP24; DM: 458; Em: 483BP32) or FITC (Ex: 482BP35; DM: 506; Em: 536BP40). Images were taken using an Andor Neo SCC-02124 camera with illumination at 80% from a SpectraX source Led (Lumencor) and exposure times of 0. 5-1 s. Nis-Elements AR software (Nikon) and ImageJ (v 1. 53f51) were used for image capture and editing.
Acknowledgements We thank  Yannick Poquet  ( IPBS, Toulouse ) and  Julien Vaubourgeix  ( Imperial College, London, UK ) for helpful discussion and critical reading of the manuscript. We thank  Life Science Editors  for editorial assistance. We thank  Emmanuelle Näser  and  Penelope Viana  (Génotoul TRI-IPBS platform, Toulouse), and  Denis Hudrisier  for help with flow cytometry,  Brice Ronsin  (Genotoul  TRI-CBI, Toulouse ) and  Serge Mazères  (Genotoul  TRI-IPBS platform, Toulouse ) for help with microscopy,  Pascal Ramos  ( Genotoul PICT-IPBS platform, Toulouse ) for technical support with NMR, and  Anne Imberty  ( Centre de Recherches sur les Macromolécules Végétales (UPR5301) CERMAV-CNRS, Grenoble ) for help with ITC. We thank  Dirk Schnappinger  ( Weill Cornell Medicine, New York, NY ) for kindly providing plasmids.
This work received funding support from the  Centre National de la Recherche Scientifique (CNRS) , the  University of Toulouse-University Toulouse III Paul Sabatier , the  Fondation pour la Recherche Médicale  ( FRM, fellowship  to  Y. M. B  and grant  n°DEQ20160334902  to O. N. ), the  JPI-AMR program  (grant  n°JPIAMR_2018_P010  to O. N. ), the  Fondation Bettencourt Schueller  ( Prix Coups  d'élan to O. N. and Expore-TB grant top O. N. ), the  Agence Nationale de la Recherche  ( ANR , grant n°ANR- 14-CE14-0024  to O. N. and P. C. , and grant  n°ANR-21-CE11-0031  to O. N. ) and  MSDAVENIR  (grant  FIGHT-TB  to O. N. ). We acknowledge support from the  Labex ARCANE ,  CBH-EUR-GS ,  ANR-17-EURE-0003. Bruker Avance III HD 700 MHz NMR spectrometer of the Integrated Screening Platform of Toulouse (Genotoul PICY-IPBS  platform) was funded by  CNRS , the  University of Toulouse-University Toulouse III Paul Sabatier, IBiSA ,  European Structural Funds , and the  Occitanie Region.
Histological Analysis Neurodegeneration. To assess the effect of LB injections on dopaminergic neurons, tyrosine hydroxylase (TH) immunohistochemistry was performed on substantia nigra pars compacta (SNpc) as previously described  [13]. Serial sections (1 to 6 slices) corresponding to the whole SNpc were incubated with rabbit monoclonal TH antibody (Abcam, EP1532Y, 1:5000) for one night at room temperature (RT) and revealed the next day by an anti-mouse peroxidase EnVision secondary antibody, followed by 3,3′diaminobenzidine (DAB) visualization. Free-oating sections were mounted on gelatin-coated slides, counterstained with 0. 1% cresyl violet solution, dehydrated and cover-slipped. TH-positive neurons of the SNpc were counted by stereology blind to the experimental condition using a Leica DM6000B microscope coupled with the Mercator software (Explora Nova, France).
Sections were incubated overnight at room temperature with the aforementioned antibody. The following day, the revelation was performed with anti-species peroxidase EnVision system (DAKO) followed by DAB incubation. Sections were then mounted on gelatinized slides, dehydrated, and cover-slipped until further analysis. Sections were analyzed by optical density (OD). The slides were scanned using Epson expression 10000XL high-resolution scanner. Images were analyzed using ImageJ open-source software (version 1. 53) to compare mean grey levels.
The raw data consist of full energy dispersive spectra for each sample pixel exposed to the beam. A thin-lm XRF reference material (AXO Dresden GmbH) was measured to calibrate experimental parameters. This was followed by elemental quanti cation through the open-source software PyMCA  [32]  in which both the reference material and the sample are modelled in terms of main composition, density and thickness. The uorescence spectrum obtained from each pixel was tted, the elemental concentration (µg/g dry weight or ppm) maps were generated, and an average elemental concentration of the SN regions was obtained.
Statistical analysis Statistical analyses were performed with GraphPad Prism 9. 1 (GraphPad Software, Inc. , San Diego, CA). For all experiments, comparisons among means were performed by using two-way ANOVA. In all analyses, statistical signi cance was set at p < 0. 05. The debate about the need to move beyond p value is raging. Data must now be analyzed further with estimation graphics  [33]  that emphasized the effect size. Therefore, all data appear as estimation graphics called 'Gardner-Altman plots': on the left of each graph, data are presented as a scatter plot showing the observed values and above de ned descriptive statistics (mean ± standard deviation). Contrast graphs using the difference axis to display an effect size on the bottom of each graph, here mean difference. Horizontally aligned with the mean of the test group, the mean difference is indicated by the black circle.
3A ). This data might indicate a reorganization of Zn concentrations away from the synapse, leading to less Zn released at the synapse  [11]. Second, we assessed the levels of ZnT4 and ZIP8, two lysosomal transporters responsible for the import and export of Zn from the cytosol to the lysosome, respectively. In the striatum, the levels of ZnT4 remained generally unchanged, with a trend towards a decrease of ZnT4 in untreated LB-injected mice (Fig. 3B ). However, ZIP8 levels were signi cantly increased in LB-injected mice having received a Zn diet, suggesting an increase in cytosolic zinc and a reduction of intralysosomal Zn in LB-treated mice with Zn impairing lysosomal function by disrupting the ionic balance in lysosomes (Fig. 3C ). This latter result would potentially explain the mechanism-based toxicity in LB + Zn-treated mice.
Conclusion Altogether, our study suggests that in vivo pharmacological chelation of Zn, by dampening Zn-mediated cytotoxicity, would result in an overall attenuation of PD-linked lysosomal alterations and dopaminergic neurodegeneration (Fig. 5 ) and may thus carry therapeutic potential. Clinical trial phases based on iron chelation with deferiprone (FAIR-PARK-I_NCT00943748) in PD patients are currently ongoing (Fair Park II), after having shown promise in certain pre-clinical models of PD  [20, 65, 66]. With this in mind, it is essential to note that heavy metal chelation as a whole, if not carefully dosed and extensively studied in pre-clinical conditions, could have detrimental effects of human patients given the widespread effect of these molecules. Therefore, this ClQ approach will require both rodent and non-human primate studies over long-term periods of time to ensure their proper clinical potential in PD patients over time.
fellowship (France). The human samples were obtained from the Brain Bank GIE NeuroCEB (BRIF number 0033-00011), funded by France Alzheimer, France Parkinson, ARSEP, and Connaître les Syndromes Cérébelleux, to which we express our gratitude. AUTHORS' CONTRIBUTIONS BD isolated fractions. MT performed the surgeries. MT and ED performed the animal termination. MT performed histologic and immunohistochemical analysis of the data. MT and MLT performed the biochemistry experiments. MT, SB, and BD performed the synchrotron analysis. MT prepared the gures. MT, EB and BD wrote the paper with input from all authors. BD, and EB conceptualized the study and designed experiments. EB and BD secured funding. FUNDING The University of Bordeaux and the Centre National de la Recherche Scienti que provided infrastructural support.
ACKNOWLEDGEMENTS We thank  Guillaume Dabée  and  Christelle Martin  for animal care, as well as  Dr. Federico N. Soria  for the script to analyze the TH-LAMP2 perinuclear fractions. The synchrotron  Diamond Light Source  is acknowledged for provision of I18 beam time (exp. SP28279). We would also like to thank  Tina Geraki  for scienti c support. MT was supported by a  Ministère de l'Enseignement Supérieur et de la Recherche.