dataesr/scientific-paragraphs-categorization huggingface dataset:
Tissues were washed (3 times in PBS1X) before being mounted with ImmuMount Reagent. Image acquisition was performed using AxioImager Z1 (Zeiss) fluorescence microscope and contrast was adjusted using Fiji software. Whole-mount floating immunostaining. Mice were deeply anesthetized with a mix of ketamine/xylazine and then L3 to L5 SC segments were rapidly dissected. Special care was provided to dissect out the arachnoid mater. The dorsal part was further dissected longitudinally and immediately placed in ice-cold PFA4% for an overnight fixation at 4 °C. Tissues were washed with PBS 1X and then saturated with BB for 1 h at room temperature, prior.
Acknowledgements We thank all the lab members for their involvement in this project and fruitful discussions. We thank  Sophie Ugolini ,  Guillaume Hoeffel  and  Anaïs Roger  from the  Centre d'Immunologie de Marseille-Luminy (CIML ) and the CIML flow cytometry platform for their support with the flow cytometry experiments. This project was founded by the  French National Agency of Research  grants  ANR-CE16- Myochronic  awarded to AM and  ANR-CE16 -Floradoloris  awarded to AR. It was also supported by founding from  CNRS  and  Aix-Marseille University  awarded to IBDM.
Materials and methods From January 2008 to January 2018, we evaluated all patients treated for low-mid rectal cancer (≤ 8 cm from the anal verge) with synchronous resectable or potentially resectable LM at the Institut Paoli Calmettes. Data were prospectively collected in a clinical database (NCT 02,869,503). The study protocol was conducted according to the 1989 World Medical Association Declaration of Helsinki and approved by our Institutional Review Board. The requirement for informed consent was waived (IPC 2020-041). Pre-therapeutic evaluations included thoracoabdominal pelvic computed tomography (CT), endorectal ultrasonography (EUS), hepatic and rectal magnetic resonance imaging (MRI), and assessment of serum carcinoembryonic antigen (CEA). These tests were repeated at each step. Inclusion criteria were fitness for neoadjuvant treatment and surgery (performance status < 3) and expected margin-negative resection (R0) of the primary disease and LM.
Statistical analysis Data analyses were performed using SPSS software (version 23; IBM Corporation, Armonk, NY, USA). Categorical variables were compared using Fisher's exact test or the chi-squared test, and continuous variables were compared using Student's t-test. The association of categorical variables with OS and DFS was assessed using the Kaplan-Meier method (based on the date of diagnosis and the relapse or censor date), and significance was tested using the log-rank test. Statistical significance was set at p < 0. 05.
Cell-Based Transport Assay by Confocal Microscopy Cells were seeded into 24-well plates at a density of 1 × 10 5 cells/well containing coverslips for microscopy and incubated for 48 h at 37 • C and 5% of CO 2. Cells that adhered to the coverslips were treated with C4a and hoechst 33342 for 30 min at 37 • C. Then, the cell monolayer was washed with PBS at 37 • C and the coverslips removed from the plate and placed on slides for microscopy. The slides were then read in a confocal microscope Nikon A1R MP + (NIKON, Tokyo, Japan) using an oil-immersed 40× objective (with the numerical aperture of 1. 15). A laser of 405 nm was used for excitation and the fluorescence emission was recorded using a bandpass filter of 425-475 nm. The software Nis Elements 4. 20 (NIKON, Tokyo, Japan) was used for visualization of the images.
Molecular Modelling The preparation of the systems and docking calculations were performed using the Schrödinger Drug Discovery suite for molecular modelling (version 2019. 4). The ABCG2 crystal structures (PDB ID: 6VXJ, bound to SN38, resolution 4. 0 Å  [30]  and PDB ID: 6VXF apo structure, resolution 3. 50 Å) was obtained from the Protein Data Bank (PDB, www. rcsb. org). The structure was chosen since it is one of the cryo-EM structures with high-resolution reported. ABCG2 structure was prepared with the Protein preparation wizard  [31]  to fix protonation states of amino acids residues, adding hydrogens and also fixing missing side-chain atoms. Missing residues for the protein (residue numbers 47-60 and 355-369) were predicted using Prime protein preparation module  [32]. Homology models were generated for both the crystal structures to predict the remaining missing residues 302-327, using the respective prepared crystal structures as templates.
In contrast, C4a stabilized the inward-open conformation of P-gp, resulting in the loss of ATP-induced dimerization of NBDs and consequently preventing thermostabilization (Figure  3B ). the C4a binding site on P-gp was slightly different from the binding site of the taxol substrate. Figure  2. In silico interaction of C4a with ABCG2 and P-gp. Molecular docking analysis in human ABCG2 (PDB: 6HCO) (A-C) and P-gp (PDB: 6QEX) (D-F). Amino acid residues are colored according to the atom involved in the interaction (carbon, light grey (chain A of ABCG2 and P-gp) and pale blue (chain B of ABCG2); oxygen, red; nitrogen, blue). (A,D) display an overview of the transporter structure, highlighting the position of the docking pose box as an orange square. The original conformation of substrates estrone-3-sulfate (E3S) for ABCG2 display small conformational changes when compared to the highest scored docking pose from molecular docking (B), while redocking of taxol within P-gp is much more expressive (E).
This additional step of centrifugation was performed to completely remove the solvent used for drug solubilization, in the case of C4a, DSMO. As proof of concept of the use of EVs as the carrier of ABCG2 inhibitors, a range of C4a from 0. 1 to 10 µM was incubated with EVs from G. intestinalis. As shown in Figure  7A , EVs containing the inhibitor (EVs G. intestinalis-C4a) caused a dose-dependent inhibition. These data revealed that C4a was incorporated into EVs from G. intestinalis after incubation and these EVs efficiently delivered C4a to HEK293-ABCG2 cells. In addition, the control performed with the supernatant containing C4a free also inhibited ABCG2 transport activity, suggesting that the drug incorporation was partial (Figure  7A ). To confirm the functional inhibition of ABCG2, an in vitro chemosensitization assay was performed.
1 to 10 µM (Figure  7B ). Together, these data represent a proof of concept that biological vesicles are powerful tools to incorporate and promote the delivery of hydrophobic drugs. To overcome the evident biocompatibility disadvantage of clinical applications of EVs of G. intestinalis as vehicles for drug delivery, we propose the use of EVs from human blood. Human EVs were obtained by two different approaches following blood collection from healthy donors: (1) circulating EVs from blood plasma and (2) EVs from blood cells after stimulation using CaCl 2 , as performed for G. intestinalis. The empty human EVs were analyzed by nanoparticle tracking analysis (NTA) and dynamic light scattering (DLS). EVs from human plasma showed a smaller size than those obtained from blood cells (Figure  S6A-C ).
1 to 10 µM. EVs containing the inhibitor (EVs human blood-C4a) inhibited the hoechst 33342 transport mediated by ABCG2 in a concentration-dependent manner (Figure  8A ). As previously observed, the supernatant containing C4a free strongly inhibited ABCG2, even in the lower concentration tested (0. 1 µM). To evaluate the use of blood-circulating EVs, the EVs from plasma were also loaded with C4a. Interestingly, the same results were observed (Figure  8B ). Together, these data demonstrate that human EVs can be used for drug delivery of inhibitors and highlight the use of plasma-circulating EVs, with the advantage of easy and rapid obtention. In order to broaden the feature of EVs, we used the same approach for the incorporation and delivery of the P-gp inhibitor, elacridar. As shown in Figure  8C, D , human blood and plasma EVs incorporated and delivered elacridar to cells inhibiting the transport of rhodamine 123 mediated by P-gp.
blood cells and (B) plasma diluted in PBS (1: 80 ) obtained by nanoparticle tracking analysis (NTA, Nanosight, Malvern, U. K. ) (C) Mean size values of EVs derived from blood cells and plasma obtained by NTA. (D) Normalized values of EVs concentration derived from blood cells and plasm obtained by NTA. (E) Mean values of the size of the empty EVs and EVs after treatment with C4a and elacridar. EVs from blood cells and plasma were diluted in PBS (1:200) and the data obtained by dynamic light scattering ( DLS, Zeta Sizer Nano Series, Malvern, UK ). Acknowledgments: TüCAD2 is funded by the  Federal Ministry of Education and Research (BMBF)  and the  Baden-Württemberg Ministry of Science as part of the Excellence Strategy of the German Federal and State Governments. The authors would like to thank  CSC-Finland  for the generous computational resources.
e. , no signs of inflammation). The probes also allow the measurement of oxygen partial pressure with excellent resolution from the area around the probe and for a prolonged time. However, several aspects need to be taken into consideration. First of all, it is uncertain how large is the area represented by the measured EPR spectrum, reflecting averaged oxygen partial pressure. The probe position was checked occasionally by ultrasound and always during necropsy, and no changes were seen. Next, even if the probe position is constant, the surrounding tumor is growing and the tumor microenvironment might be changing during tumor development. That is why data interpretation needs to be limited to probe localization, rather than generalized to the whole tumor. To sum up, data interpretation can be challenging, especially for heterogeneous tissue.
EPR and US data analysis EPR data analysis was performed with the use of custom MATLAB (Mathworks, USA) scripts. Recorded EPR spectra were fitted using EasySpin toolbox, and the spectrum line width was measured. Oxygen concentration was calculated from the spectrum line width based on the calibration curve determined in buffer solution bubbled with a range of oxygen concentrations. Ultrasound data analysis was performed in Vevo LAB 3. 2. 0 (VisualSonics1, Canada) software. From each image, blood flow voxels within the tumor border were counted. Tumor borders were delineated by hand in all B-mode image slices. The tumor volume and vascularity (percent of functional vessel volume in tumor volume, VP) were calculated.
To highlight the influence of each given dose, some analyses were performed as a function of the number of injections (Figs 2-4, S2 and S3). Data was analyzed in Statistica131 software with multifactorial and repeated measurements ANOVA to determine significant effects of factors like ITPP or tumor oxygenation status. For pair analysis, Kruskal-Wallis ANOVA was used. P<0. 05 was considered statistically significant. The same pO 2 experimental data from tumors is presented differently in Figs  1 2 3 and S1-S3. Raw data are accessible via Jagiellonian University repository (RODBUK) with DOI number: doi:10. 57903/UJ/K3QDYS.
In addition, pO 2 data were not collected for C57BL/6J mice after the sixth saline dose due to the loss of mice for ethical reasons. A significant effect was observed in B16F10 tumors treated with 6 ITPP doses at days 5,6,11,12,17 and 18 post-tumor inoculation, where local pO 2 levels increased after dose five to 14. 6±9. 55 mm Hg, whereas in control animals, it was 8. 5±6. 61 (p = 0. 024). Similarly, after the sixth ITPP dose, local pO 2 was 15. 6±6. 38 mm Hg for ITPP-treated animals and 5. 5±3. 37 mm Hg for saline-injected mice (p<0. 002). A significant increase in local pO 2 level was also observed in B16F10 tumors treated with the second ITPP protocol (6 injections at days 5,6,12,13,19, and 20 post-tumor inoculations). After the fourth ITPP dose the increase of pO 2 was from 9. 3±3. 97 mm Hg for saline-treated animals to 15.
Acknowledgments We gratefully acknowledge the gift of  OxyChip from Periannan Kuppusamy Geisel School of Medicine at Dartmouth College. We thank  Eryka Moskal  and  Kinga Szuba  for their help with animal imaging. The authors thank  Professor Jean-Marie_Lehn ,  ISIS, University of Strasbourg , 8 Allee Gaspard Monge, 67083 Strasbourg, France; and  Professor Claude Nicolau , Friedman.
Study selection and data collection To begin, titles and abstracts were analyzed, and studies that did not fulfill the eligibility criteria were excluded. Afterwards, the full texts of the remaining studies were evaluated to determine their inclusion or exclusion. Each evaluator (PM and CA) compiled a separate list of articles to be included according to the eligibility criteria. The lists were then compared and disagreements were solved by dialogue and consensus. From each selected study, the following information was collected: authors; trial name; phase of the study (induction or maintenance); period of data collection; publication year; cohort's region/ country of origin; the type of treatment (identity of the biologic agent); placebo only; duration of the study; disease duration; number of patients enrolled in the intervention and the placebo groups;.
Outcomes and summary measures The outcomes were the proportions of clinical remission and clinical response observed in the group treated with the biological drugs compared with those of the placebo group. Clinical remission and clinical response definitions were used as reported in the individual studies. In the event of multiple treatment groups, data were synthesized by combining groups to create a single pair-wise comparison as recommended by Cochrane. 12 This same rule was applied whenever studies did not report global values regarding disease duration; thus, medians were used as a summary measure. In addition, we performed a sub-analysis of the maintenance studies by identifying which presented a funnel approach to the trial design, that is, by not allowing patients who did not achieve the outcomes to continue the study (Supplementary Figure  1 ).
Statistical analysis Data were extracted or calculated and the two groups (intervention and placebo) were compared to estimate absolute proportions, OR, and 95% confidence interval (CI) for clinical remission or response. The Mantel-Haenszel random-effect method, which considers variance as a summary of the study-level heterogeneity, was used. Statistical heterogeneity was assessed using the Cochran χ2 method and the I 2 statistic (substantial heterogeneity was assumed if I 2 > 50%). each study was based on the time period in which they were conducted. Moreover, by using meta-regression analysis, we tested the effect of the publication year, disease duration, prior anti-TNF exposure, and prior immunomodulator (IM) exposure on the odds of achieving the relevant clinical outcomes. Both the Harbord test and visual analysis of funnel plots were used to detect potential publication bias.
Literature search and study selection The electronic database search yielded 5654 records (2580 records in MEDLINE-Pubmed, 1155 in Cochrane Library, and 1919 in ISI Web of Science); the manual search did not identify any additional studies. After removing duplicates (n = 998), 4656 records remained, of which 3316 were excluded. The remaining 106 were assessed for eligibility. Eighty-two studies were excluded following the eligibility assessment, resulting in a total of 25 trials selected for inclusion in the systematic review (Supplementary Figure  2 ).
MED-LINE (via PubMed), Cochrane, and ISI Web of Science databases were searched from inception to 15 March 2022, with the following keywords or medical subject heading (MeSH) terms (Crohn's disease [MeSH Terms] odds ratio (OR) Crohn's disease OR IBD [MeSH Terms]) AND (randomized controlled trial OR trial OR randomized clinical trial (RCT)) AND (biologics OR biological therapy OR infliximab OR anti-TNF OR vedolizumab OR adalimumab OR certolizumab OR ustekinumab OR risankizumab) AND (clinical remission OR clinical response OR endoscopic remission OR biomarkers OR mucosal healing OR histologic remission). No publication date or language restrictions.
Bioinformatics and phylogenetic analysis Basecalling and demultiplexing of the newly sequenced chimpanzee isolates was performed via bcl2fastq v. 2. 19. 0. 316. Resulting fastq data were quality assessed and adapter trimmed with fastp v. 0. 20. 1  35. Genetic variants were called using the snippy pipeline  36  with default parameters and variants were annotated by means of SnpEff v. 5. 1  37. A SNP-alignment was extracted via snp-sites v. 2. 5. 1  38  and a suitable DNA-evolution model for phylogenetic inference was chosen utilising modeltest-ng v. 0. 1. 7  39. The chromosomal Bcbva phylogenetic tree was built in a maximum likelihood framework using RAxML-NG v. 1. 1  40  , starting from 20 random and 20 parsimony trees. The best scoring ML tree was resampled with 500 bootstrap replicates to calculate transfer bootstrap expectancy (TBE) branch support values  41.
The same cortical area (primary visual cortex, analogue of Brodmann Area 17) was analysed in all cases to account for known variation of density and cortical distribution of PNNs between cortical areas  51. Counts were performed on a Zeiss AxioScan. Z1 (Zeiss, Jena, Germany) using Zen Blue software 3. 6 (Zeiss, Jena, Germany). Relevant cortical regions were delineated at low magnification and three frames were placed in a systematic-consecutive fashion in the delineated regions. Neurons within each frame (250 x 2500 µm) were counted at higher magnification (20x, NA 0. 8, ~350nm). Three sections and six frames per case were investigated. The number of PNNs was converted to numerical density per mm 2. Bcbva load was quantified on consecutive Nissl sections. Percentual area coverage with Bcbva was estimated using AI software module Intellesis Zen Blue 3.
Acknowledgements We are grateful for research and brain extraction permissions in Sierra Leone to  Environmental Protection Agency ; in Côte d'Ivoire to the  Ministère de l'Enseignement Supérieur et de la Recherche Scientifique  and the  Ministère de Eaux et Fôrets in Côte d'Ivoire. We are grateful to the  Centre Suisse de Recherches Scientifiques en Côte d'Ivoire  for their logistical support, the staff members of the  Taï Chimpanzee Project  and the  Tacugama Chimpanzee Sanctuary  for their support and assistance in collecting the samples and data. We especially thank  Christina Kompo  for adeptly handling import and export permits and shipping.
Study Design and Overall Procedure We conducted a cross-sectional study, with retrospective data collection of injury complaints related to the athletics activity, using a self-reported online survey system (LimeSurvey), asking elite sprinting athletes in explosive disciplines requiring sprints (i. e. , sprints, hurdles, combined events, and jumps), to report their injury complaints during their lifetime athletics activity, allowing them also to report the injury complaints during the one-year period before the survey and at the time of the survey. The present study was approved by the Committee for the Protection of Persons (CPP Ouest I-Tours, number: 2021-A02523-38).
Population The eligible population consisted of athletes (i) licensed with the French Federation of Athletics (FFA), for (ii) competitive athletics activity in explosive disciplines requiring sprints (i. e. , sprints, hurdles, combined events, and jumps), and (iii) listed in the Sport Ministry repository of "elite athletes" or being elite athletes sparring partners, and (iv) competing at least at the international or national level. Eligible athletes were contacted to participate in this study (i) by the research team directly or indirectly via their coaches or (ii) by the technical national director of the FFA directly or indirectly via their coaches. They were informed about the study aim and procedure and that their data would be used for research, as well as about their rights. Eligible athletes interested in participating in this study were included if they agreed to participate, signed the informed consent, and completed the online survey.
Data Collection Data were collected using an online survey (LimeSurvey). This online survey was developed by one sports medicine physician with experience in injury epidemiology in athletics (P. E. ), two researchers in sport psychology (B. C. and A. R. ), and three researchers in sport biomechanics (C. G. , C. H. , and G. G. ). This online survey was developed with the goal of exhaustively collecting injury complaints related to the athletics activity of the included athletes based on the "International Olympic Committee consensus statement: methods for recording and reporting of epidemiological data on injury and illness in sport"  [16]. The survey was divided into two parts (Supplementary Materials): (1) information on anthropometrics and athletics activity: age, sex, body mass, height, main athletics discipline (i.
, muscle, tendon, ligament, bone, articular, nerve, skin, others  [6] ), the circumstance of occurrence (training or competition), the mode of onset (sudden or gradual), the injury mechanisms (clearly identifiable injury with contact, clearly identifiable without contact, or not clearly identifiable), and the severity (i. e. , the duration of absence in sports due to the injury complaint (none, less than 7 days, between 7 and 28 days, or more than 28 days)  [16]. The survey was tested by two sports medicine physicians and four sports scientists, until the final version was validated by the group of the six initial developers; it was not tested on the targeted population. Data were collected using the survey from 31 August 2021 to 10 November 2022. Athletes who agreed to participate in this study were asked to complete the online survey.
Our present results confirm that injuries are part of the elite sprinting athletes' life  [1] , because almost all athletes included in this study already experienced at least one injury complaint. This outcome extends the knowledge to the specific population of elite sprinting athletes for which datasets are scarcer than for less trained populations. In addition, the 1-year prevalence proportion of 62% was comparable to that previously reported in athletics in other populations  [8, 10, [12] [13] [14] [15]. Therefore, our results seem to confirm that about two-thirds of athletes participating in athletics have an injury complaint during an athletics season. It seems to be a constant in athletics, whatever the population, study design, injury definition, level, sex, or discipline  [8, 10, [12] [13] [14] [15].
Data analysis From the load and displacement values, the fracture load and fracture displacement were identified for each Fig. 2  The dowelplasty system (Sycamore, Safe Orthopaedics, Eragny sur Oise, France) implanted into a vertebra specimen. Furthermore, energy absorbed at fracture was calculated by multiplying the fracture load and fracture displacement, while stiffness was taken to be the slope of a linear model fitted to the load-displacement curve that was forced to have a y-intercept of zero. Descriptive statistics were used to summarise the data. Differences between pre-and post-treatment values were calculated as net changes. Effect sizes were calculated as mean differences between treatment groups with their 95% confidence intervals (CI). Since there were less than 30 samples, data was assumed to be non-normally distributed  [6].