dataesr/scientific-paragraphs-categorization huggingface dataset:
Subjects First case study: Assessing mobility in visually impaired subjects with retinitis pigmentosa. A prospective study included 17 visually impaired subjects with RP and 10 fully sighted control subjects (CO) recruited at the Quinze Vingts National Ophthalmology Hospital in Paris, France. The study was conducted according to the principles of the Declaration of Helsinki and approved by an ethics committee (Comité De Protection Des Personnes Ile -De-France (CPP) V, Paris, n °EudraCT: 2015-003400-24). Informed written consent was obtained from all participants. The RP inclusion criteria were clinical diagnosis of RP confirmed by visual assessment and retinal electrophysiology, binocular VF < 40 degrees, and VA ≤+ 0. 3 logMAR. The CO inclusion criteria were VA ≤+ 0. 1 logMAR and normal VF.
Area and horizontal and vertical diameters were collected. As there was no significant difference between these 3 types of measures, horizontal VF was used for data processing and all VF references in this article. Dark adaptation (DA) was measured with Metrovision MonPackOne, Perenchies, France, in binocular vision: measurements started with a light adaptation phase (300 cd/m ²) lasting 5 minutes, followed by a DA phase lasting 20 minutes to determine visual sensitivity recovery. Study population and visual tests are summarized in Table  1. Mobility assessment: Mobility was tested in 3 light settings: one at high illumination level (235 lux) and two at low illumination levels (1 and 2 lux) ( Figure  7  ). Four indoor courses (A, B, C, and D) comprising the same obstacles and length conditions were designed within the Streetlab artificial street platform ( Figure  1  ).
• ASSESSING FUNCTIONAL VISION: First case study: Assessing mobility in visually impaired subjects with retinitis pigmentosa Visual field assessment in subjects with retinitis pigmentosa. Area and horizontal and vertical diameters were collected. As there was no significant difference between these 3 types of measures, horizontal VF was used for data processing and all VF references in this article. Table  1  contains demographic data and clinical measures of visual function for both RP and CO subjects. Within the RP group, the visual function measures were all correlated (from P =. 0003 to P <. 0001), except DA 10' and VA ( P =. 108). Mobility assessment in subjects with retinitis pigmentosa. As shown in Figure  16  , poorer results were observed in the RP group than in the control group for PWS, PPWS, WIT, and number of collisions for both low illumination ( P <.
Based on better understanding of the retinal degeneration process and the encouraging results from the AAV-RPE65 gene replacement approach and its marketing approval, pioneering clinical studies were initiated to evaluate the safety and efficacy of gene therapy in other monogenic eye diseases, such as choroideremia (CHM) (NCT01461213, NCT02341807, NCT02077361, NCT02553135, NCT02671539, NCT02407678), Xlinked retinoschisis (NCT02416622, NCT02317887), Usher syndrome (NCT01505062), ABCA4 -associated Stargardt disease (NCT01367444), CNGA3 -linked achromatopsia (NCT02610582, NCT02599922), MERTK -associated retinal disease (NCT01482195), and RPGR -associated RP (NCT03252847, NCT04312672, NCT03316560, NCT03316560, NCT04671433); and promising safety profiles were demonstrated from MERTK  32  and CHM  33 , 34  trials.
A gene therapy product (GS030) encoding the red shifted channelrhodopsin variant ChrimsonR was produced by the French biotech company GenSight Biologics for delivery via the engineered AAV vector AAV2 7m8. 52 This gene therapy, designed to confer a photoreceptive function to the preserved retinal ganglion cells, is supported with biomimetic goggles that capture visual information and amplify the light stimulation upon the transduced neuronal cells at the appropriate wavelength. A dose-escalation study (PIONEER; NCT03326336) was initiated to evaluate the safety and tolerability of GS030 in subjects with RP. Being independent of the genetic cause of the retinal dystrophy, the optogenetic approach can be applicable to a broad range of patients with rare genetic diseases of the retina (such as RP), as well as to more common retinal degenerative diseases, such as age-related macular degeneration.
In parallel to the optogenetic approach, retinal prostheses have the demonstrated ability to reactivate remaining retinal circuits at the level of bipolar or ganglion cells after photoreceptor loss. We have been involved in both the validation and registration of the Argus II prosthesis and in the preclinical/clinical development of PRIMA, as described below. Both epiretinal (Argus II; Second Sight Medical Products) and subretinal (Alpha IMS; Retina Implant AG) implants were proved to restore partial vision in blind people with IRDs. 13 , 53 They have both received market approval in Europe and in the United States, but their production was suspended in 2019. Wireless subretinal prosthesis PRIMA (Pixium Vision) is currently under clinical evaluation in France and the United States (NCT03333954, NCT03392324).
Our future research will adapt such methods and enable a better understanding of patients' feelings about their visual impairment and the future, the impact on their independence, and their ability to interact with health providers and services, as well as the influence of social determinants of health and of education. The importance of these cannot be overstated. Such knowledge should guide better therapeutic strategies, including rehabilitation, and reduce social exclusion and stigma, while helping patients to develop psychological resources and social engagement. Funding/Support: Programme Investissements d'Avenir IHU FOReSIGHT (ANR-18-IAHU-01), Programme Investissements d'Avenir LabEx LIFE-SENSES (ANR-10-LABX-65), European Research Council (ERC) Synergy Grant "HELMHOLTZ", Foundation Fighting Blindness.
Q (query) fever is an infectious zoonotic disease caused by the Gram-negative bacteria Coxiella burnetii. Although the disease has been studied since decades, it still represents a threat due to sporadic outbreaks across farms in Europe. The absence of a central platform for Coxiella typing data management in an important epidemiological gap which is relevant in the case of an outbreak. To fill this gap, we have designed and implemented an online, open-source, and, web-based platform called CoxBase (https://coxbase. q-gaps. de). This platform includes a database that holds genotyping information of more than 400 Coxiella isolates alongside metadata that annotates them. We have also implemented features for in silico genotyping of completely or minimally assembled Coxiella sequences using five different typing methods, querying existing isolates, visualization of isolate's geodata via aggregation on a world map and submission of new isolates.
All methods allow to detect a correlation between geographic origin and genotype and are useful for typing strains in endemic regions as well as clinical entities (5)  (10). MLVA, MST and IS1111 methods offer a higher resolution compared to the other two methods  (5). A researcher interested in typing a new Coxiella strain is likely to employ more than a single method to obtain quality proof or at least to employ the methods accessible in his particular setting. Access to a database resource with strain information and metadata will be necessary for comparison purpose. Presently there are two of such resources that house Coxiella genotyping data. The first is the MLVA databank (http://mlva. i2bc. paris-saclay. fr/mlvav4/genotyping/) and the second is the MST database (https://ifr48. timone.
univmrs. fr/mst/coxiella burnetii/), for the other genotyping methods there are no available database resources. First we sought to overcome the lack of additional genotyping resource, then we sought to consolidate on the existing resources via introduction of new features such as visualization of allelic reference for MST typing, aggregation of MLVA groups and introduction of MLVA genotypes for better comparison. To this end, we have developed an online, open, web-based platform called CoxBase, which caters for vital aspects of internet based Coxiella research. This platform also includes a database that contains over 400 C. burnetii isolates from different countries. It has been implemented with a user interface for quick retrieval of isolate information as well as a submission channel to add to the growing body of new Coxiella isolates.
Also, we sought to unify all Coxiella typing systems under a single platform, alongside all the published details of Coxiella genotyping, including primers for genotyping protocols, as well as phenotypes, for the purpose of strain discovery and comparison. We implemented an in silico genotyping option for all major genotyping systems of C. burnetii based on whole genomic sequences. Finally, we included visualization systems to quickly summarize all metadata on country level, maps for enhanced geographic localization of isolates and a worldwide distribution map of all C. burnetii isolates in our database. Here, we present our platform, its current scope, usage and capabilities.
Webserver components The server is run by Apache HTTP server (version 2. 4. 29), on a machine hosted by de. NBI Cloud services. The server components can be grouped under 2 main sections, the front end and the back end. The front end. The main component of the front end is the web user interface, this is designed to accept user queries as well as submissions, send data to the back end and present data back to the user. Styling was achieved through an assortment of the cascading style sheet (CSS) Bootstrap framework (https://getbootstrap. com/), jQuery UI library and custom CSS style scripts. The validation of forms and events processing is achieved with JavaScript. The user interface accepts two kinds of data input: FASTA formatted whole genomic sequence (contigs or complete assembly) for typing purposes, and typing profiles via multi locus variable number tandem repeat analysis (MLVA)  (7)  and Multilocus sequence typing (MST)  (8)  for isolate comparison and discovery.
MLVA typing: The MLVA typing feature accepts as input, genomic sequences either as contigs or complete assembly in FASTA format. The lengths of fourteen MLVA amplicons (when present) are extracted in silico with the e-PCR tool (13) using primers from Frangoulidis et al. , 2014 (Table  1 ) (7) updated in http://mlva. i2bc. parissaclay. fr/MLVAnet/spip. php?rubrique50. The repeat number is calculated with the formula below : RN = (AL-FL) RS (1) where RN = repeat number, AL = amplicon length, FL = flanking length and RS = repeat size. For every submitted job, a unique identifier is generated that can be used to retrieve the results historically from the database within three weeks after the date of submission. The results of the MLVA typing are presented in form of a table with all the calculated parameters.
MST typing: The in silico MST method accepts genomic sequence in FASTA format. The first step is amplicon detection via USEARCH  (14). This is done using the MST primers from  Glazunova et al. , 2005 (8). The allele type is determined by aligning detected amplicon sequence globally with known alleles in the MST library (https://ifr48. timone. univmrs. fr/mst/coxiella burnetii/spacers. html). Novel sequences with no match are also reported. The detected MST profile can be used as a query to the database to find the corresponding MST group.
Isolate discovery and comparison The CoxBase platform offers features for the discovery and comparison of Coxiella strains through several approaches. One approach is to query the database based on metadata and genotype features like country, host type, plasmid type, year of isolation, MLVA genotype and MST group. The advantage of this approach is that it's fine grained and the fields can be aggregated to build more specific queries. Another approach utilizes a faceted search, this approach is more suitable for refining queries based on reviewed criteria. Other approaches rely on making queries based on known typing profiles via MLVA or MST typing schema. This is implemented as follows: For a user who wishes to discover isolates with a specific isolate profile (MST or MLVA). They need to provide a complete or partial profile (MLVA or MST) of the isolate which they are interested in.
Data collection sets and Testing We tested our implementation on fifty Coxiella whole genomic sequences from RefSeq. (Table of genomes in supplementary table). We had eleven complete chromosome assembly, thirteen chromosome assembly, fifteen contigs and eleven scaffolds. The average genome size was 2. 01Mb. Forty of these were of unknown genotypes (not published if known), so we sought to type these genomes as well. The genome sequences in FASTA format were downloaded from the RefSeq database and stored without any form of modification. The genomes were typed individually using the different typing methods on our platform. After which the results were compared to known strains in our database. The results are discussed below.
AdaA and Plasmid typing The plasmid of the twenty-three genomes out of the fifty genomes in the dataset were already known. We were able to confirm the known plasmid type and extended the information with their adaA gene phenotypes, and for genomes whose plasmid type was not known we were able to detect the plasmid type as well as their adaA gene phenotypes. We determined 43 out of the 50 genomes carried a plasmid. QpH1 was present in 34 instances. Nine out of the fifty genomes had an adaA deletion phenotype and the remaining were adaA wildtype. Out of the 41 positive strains, seven had a repeat insertion in there adaA gene sequence, while four genomes showed a SNP at position 431 of the adaA gene sequences. We observed that six out of the seven genomes with an adaA repetition phenotype belonged to the same MST profile.
burnetii in an epidemiological context. We have leveraged on technologies such as NGS, cloud computing and database to create an open web resource that can be used to genotype draft or completely assembled C. burnetii genomic sequences as well as compare them to existing strains. Our approach also brought together different aspects of Coxiella research including epidemiological surveillance, sequence analyses and phylogeny under a single platform. The strength of in silico typing methods rely on, to a significant degree, the quality of the input sequence. We observed that certain MLVA markers are also not as effective as others, however, a combination of multiple markers of different typing schemes should improve the averaging effect. Nevertheless, our implementations suggest that in silico typing can be an indispensable tool for rapid genotyping of Coxiella genomic sequences.
ACKNOWLEDGEMENTS This research has been funded by the  Federal Ministry of Education and Research of Germany (BMBF , project number  01KI1726E ). Furthermore, the work was supported by the  BMBF-funded de. NBI Cloud within the German Network for Bioinformatics Infrastructure (de. NBI)  ( 031A537B ,  031A533A ,  031A538A ,  031A533B ,  031A535A ,  031A537C ,  031A534A ,  031A532B ).
CyFi-MAP is an open-access resource with specific, curated and continuously updated information on CFTR-related pathways available online at https:// cysti cfibr osism ap. github. io/. This tool was developed as a reference CF pathway data repository to be continuously updated and used worldwide in CF research. Omics technologies revolutionized the way researchers generate data 1. The integration of disease-specific data allows not only to capture knowledge at its multiple levels of organization but also to unbiasedly identify molecular features, such as phenotypes associated with complex and heterogeneous diseases-which would remain otherwise unnoticed 2,3. The visual representation of molecular mechanisms has emerged as a powerful tool for a better understanding and analysis of specific disease-causing features.
S2  in Supplementary material), (2) the glycosylation (i. e. , form B or C) and folding status (N-glycosylation) of CFTR, (3) the proteins that bind uniquely to the F508del-CFTRprotein, (4) identification of eachlife cycle steps included-additional information in Supplementary material, and (5) cell organelles specific interactions represented through images, with the entities (i. e. , proteins, complexes, ions, and others) adequately located in the biological compartments, differentiating between organelle lumen and the cytosol. CyFi-MAP navigation. Map availability. The source of these schemes are available at the map online repository (https:// cysti cfibr osism ap. github. io/) and the CyFi-MAP can be accessed online and explored interactively via the Molecular Interaction NetwoRks VisuAlization (MINERVA)  37.
Online and interactive navigation. In the form of an interactive diagram via the MINERVA platform (Fig. 2 ), CyFi-MAP provides the capacity to easily follow CFTR interactions starting with its folding until degradation, with every intermediate step described (see supplementary material). The MINERVA platform allows easy navigation and exploration of the CF related molecular pathways available in CyFi-MAP. The user can also zoom in and find various details about proteins of interest (such as location of their interactions with other biological elements inside a cell, information on the protein name/alternative names and identification names in several databases such as Ensembl, human gene nomenclature, UniProt etc. ; the annotation information is linked to the biological resources via direct urls).
The folding of CFTR is highly regulated in the ER before the protein is allowed to proceed along the secretory pathway to the PM. This information is represented in the Folding module at both submaps hence, it is possible to visualize it side-by-side in the GitHub link. Beginning with thewt-CFTR, folding starts with the nascent CFTR CFTR polypeptide chain being translocated to the ER membrane (step [1]), after which the N-glycosylation occurs (step [2]), a posttranslational modification during protein synthesis in the ER that is critical for PM expression and function (Fig. 3A )  [38] [39] [40]. In CyFi-MAP, the different glycosylation states of wt-CFTR are represented and possible to follow. N-glycosylation starts with the addition of oligosaccharide residues (glucose3-mannose9-N-acetylglucosamine2) to CFTR (Fig.
Yet no final curative treatment has yet been developed for CF disease  [64] [65] [66]. The increasing data available on public databases lead to the improvement of tools to filter and extract relevant knowledge required for the discovery of therapeutic targets. With this need, disease maps were developed as a multilayer-readable network that allows representing increasingly complex and extensive information in In the image A two types of internalization of wt-CFTR are present, through clathrin coated vesicles [19] and through caveolae vesicles [20]. As is represented, in the first, several proteins are involved, since the clathrin triskelion complex to cytoskeletal F-actin-MYO6 complex and other proteins assisting the process. In rF508del-CFTR, only the complex Caveolin 1 (CAV1)/ Caveolin 2 (CAV2) was found in this protein endocytosis [9], with assistance of Flotillin 2 (FLOT2).
Methods CyFi-MAP construction. The development of the CyFi-MAP follows the disease map development protocol, using primarily  Kondratova et al. and Mazein et al. 11, 74. Specifically, three main steps entail the construction of CyFi-CFTR (Fig. 8 ): I. The first step consisted of searching relevant CFTR-related information, selecting a total of 297 research papers and more than 1000 reviewed articles. A complete list of publications consulted for the CyFi-MAP development is available in https:// cysti cfibr osism ap. github. io/. The CF disease hallmarks were obtained from peer-reviewed research papers, domain experts' suggestions and advice, previously documented and validated pathways, and curated up-to-date databases (including Reactome 6 /KEGG 4 /MetaCore from Clarivate Analytics. Please see Content curation subsection for details).
g. same colour for nodes/ edges, curved connectors) to an individual or multiple elements; (ii) algorithms for automatic layout (details on using yEd to automatically layout SBGN-related diagrams are given in e. g. 75 ). The yEd Editor also incorporates the SBGN Palette that permits the direct representation of the SBGN-specific elements into the yEd inner GraphML format. After the CyFi-MAP was developed in yEd, we converted it into the SBGN standard format by using the ySBGN converter, (a bi-directional converter between the SBGN and yEd GraphML formats, available at https:// github. com/ sbgn/ ySBGN). Further, the CyFi-Map SBGN diagram was loaded to the MINERVA online platform. The organelle images (developed manually and expert-revised) aim to facilitate visualisation of the mechanisms at the top level; thus, special attention was given to the localization of the interactions in each organelle.
Content curation. The data used in CyFi-MAP was obtained by manual human search, curation and validation with domain experts in three main sources: Pathway databases. The curation process started by reviewing previous attempts to summarize CF information in these signalling networks. Pathways from MetaCore (Clarivate Analytics), Reactome and KEGG were Starting by the research and curation of data contained in general and CFTR-specific databases and peer-reviewed research papers, CyFi-MAP was constructed based on domain experts' suggestions and users' comments. The organization of the curated data required the selection of a general format to be used throughout the platform, which determined the map assembly and content visualization. After the map was built, domain experts were once again consulted, in order to review and provide feedback on the accuracy of the representation of the disease mechanisms, as well as the usability of the platform.
reviewed in order to analyse the pathway availability for the CF disease  6, 76. Major CF-related pathways were retrieved from these databases and confirmed in the literature for their accuracy. Literature. The main hallmarks of CF were extensively searched in PubMed. As CFTR is the protein that plays a central role in the map, direct interactions with it were very carefully selected, following strict criteria. Considering that the lung is the most affected organ, the focus was on human airway epithelial cells studies. The massive number of CFTR reviewed articles and studies available were analysed and selected as particularly relevant; results obtained from essays with other relevant cell types (such as intestinal epithelial cells) were also included when validated by review papers, meaning they are accepted by the scientific research community.
Databases. Among the web resources used for data gathering, the most significant were GeneCards 78 , Stringdb  79  , Biogrid  80  , UniProt  81  and HGNC (HUGO Gene Nomenclature Comittee)  82  which were used to confirm the correct names of proteins/genes, their known function and their interactors. For each protein, the name was checked in HGNC. UniProt and Genecards were used to search for alternative names for the same protein so as to find the correct HGNC designation  78, 81, 82. Often, although a protein complex is known to interact/participate in a CFTR process, the specific proteins that constitute that complex are not described in the original literature report. CyFi-MAP curation process. The curation process developed presents 5 levels. 1st level filter the data to studies with proteins that interact directly with CFTR, meaning that only experimental techniques which confirmed a direct interaction were considered such as e.