dataesr/scientific-paragraphs-categorization huggingface dataset:
Scaffolding lncRNA candidates display functional features To determine if our scaffolding lncRNA candidates are likely to be functional, we gathered several orthogonal datasets of lncRNAs displaying functional features. Together these include lncRNAs (i) displaying a metabolism profile characteristic of functional transcripts  (35) , (ii) overlapping eQTLs (36); (iii) that alter cell-growth when subjected to inactivation by CRISPRi (37); (iv) involved in disease  (38, 39) , as well as lncRNAs (v) conserved in tetrapods  (40)  or (vi) possessing structurally conserved elements  (41). Strikingly, even though these functional lncRNAs have been found to act not only through protein-binding but also RNA-and DNA-binding, many were successfully identified by our protein-RNA interaction-based approach (Figure  5A ).
Indeed, we observe a significant (P-value < 0. 05, onetailed Fisher's exact test) and often strong overlap (OR > 2) between our scaffolding lncRNA candidate dataset and every functional or conserved lncRNA dataset analysed except therian-conserved lncRNAs. This latter result suggests that most human scaffolding lncRNAs may have appeared later in evolution or may be highly species-specific. Additionally, when considering the different sets of scaffolding lncRNA candidates identified using our four different protein group datasets separately, they are all found significantly enriched in functional or conserved lncRNAs from all tested orthogonal datasets (P-value < 0. 05, OR from 1. 73 to 1. 96, one-tailed Fisher's exact test; Supplementary Figure  S6A ). Different pertinent lncRNA candidates can therefore be detected from each protein group dataset, consistent with the relatively low overlap observed between lncRNAs candidates found from each dataset (Supplementary Figure  S6B ).
LncRNA-associated disease mechanisms could involve lncRNA scaffolding function Hundreds of lncRNA genes have been associated with several human diseases and conditions including cancer, diabetes and neurodegenerative diseases. As most of these associations were identified through the analysis of lncRNA differential expression in disease states  (38, 39) , knowledge on the molecular role of these lncRNAs in disease is lacking. We have found 30 scaffolding lncRNA candidate genes associated with disease in lnc2cancer  (38)  and LncRNADisease (39) databases (Figure  5A ; Supplementary Material). We then assessed whether these lncRNA-disease associations could occur through the predicted protein group scaffolding functions of the lncRNAs. For this, we mapped proteins involved in disease from the OMIM database  (43)  to protein groups and found that 15 out of 30 scaffolding lncRNA candidate genes associated with disease are possibly interacting with a protein group that includes at least one protein associated with the same or similar disease (Figure  6 ; Supplementary Table  S5 ).
For this, we used catRAPID, a protein-RNA interaction predictor based on the physicochemical features of the molecules, which can be used large-scale and has been initially validated on a large collection of protein associations with lncRNA  (24). Indeed, catRAPID performed well against the NPInter database (area under the receiver operating characteristic (ROC) of 0. 88), as well as on the non-nucleic-acid-binding database (area under the ROC curve of 0. 92)  (31). In addition, we showed herein that catRAPID predictions provide relevant information about lncRNA-protein-complex interactions by experimentally validating that part of the Pur␣-Pur␤-YBX1 complex --predicted here to interact with the lnc-405 lncRNA --effectively binds the lncRNA in vivo. Noticeably, as the catRAPID predicted interaction network contains the set of biophysically possible interactions between co-expressed molecules, which may differ from in-   53 ) and  (52).
Overall, these reasons justify our integration of several orthologous functional datasets to validate our interaction predictions and the possibility of the lncRNA to be indeed functional in the cell. A growing body of evidence suggests that a significant fraction of lncRNAs has a function  (36, 37). Large-scale efforts to determine or predict lncRNA function have used their metabolic properties  (35, 36) , sequence or structural conservation  (40, 41) , differential expression in disease  (56) , lncRNA and protein-coding gene co-expression profiles  (57) , variant analysis  (58) , as well as combinations thereof  (59). Methods to understand the function of individual lncRNAs through direct interaction with proteins have been exploited to a lesser extent, and are generally restricted to the limited number of known RBPs assessed to date.
This suggests the identification of human lncRNAs is far from complete, but also that lncRNA identification methods are not yet convergent  (64). In our study, we therefore restricted our analysis to lncRNAs from the curated dataset of GEN-CODE, widely considered as the human gene annotation reference standard. However, this also means that several recently found lncRNA scaffolds such as the LUNAR-1 (65), linc-RAM  (66)  and PARTICLE (67) lncRNAs are not yet present in the GENCODE dataset. Importantly, we identified for the first time 847 lncR-NAs, accounting for ∼5% of the human long non-coding transcriptome, that potentially act as RNA scaffolding molecules for a total of 1517 protein complexes or modules, roughly half of the human protein complexes known to date. As for protein-RNA interactions, knowledge of the human protein complexome is not yet comprehensive.
Therefore, we used several datasets of protein complexes to better cover the protein complex space. Indeed, these datasets are largely non-redundant, with 0 to 12. 4% of complexes sharing > = 50% of their constituent proteins with another complex of the same dataset (Supplementary Table  S6 ). In addition, the three datasets are largely complementary, with at the most of complexes ≥50% of their proteins between datasets (Supplementary Table  S7 ), and none of the complexes being entirely shared between datasets. A slightly higher inter-dataset overlap (26. 2%) is found for network modules, mostly due to the higher module size compared to the protein complexes. As expected, we found that each protein group dataset used allows identifying a different set of scaffolding lncRNA candidates and the majority of the candidates (57%) are detected exclusively with one dataset of protein groups (Supplementary Figure  S6B ).
Overall, this reveals the necessity of considering several datasets for a global analysis of human cellular complexes, as performed in this study. Notably, our study indicates that RNA scaffolding may be an important regulatory mechanism, not limited to the few well-known cases. We indeed greatly expand the current knowledge on RNA-mediated scaffolding, by proposing that scaffolding occurs with a high prevalence and for most cellular processes. Even though major cellular functions such as telomere repair, signal peptide recognition and translation are known to closely involve RNA components, usual methods to identify cellular macromolecular complexes routinely use an RNA nuclease step before protein purification (2), thereby hindering the possible detection of RNA components in protein complexes.
FUNDING Work in IB's lab was partially supported by grants from  ERC-2013  [AdG 340172-MUNCODD]; Telethon [GGP16213];  Human Frontiers Science Program Award  [ RGP0009/2014 ];  Parent Project Italia, AFM-Telethon [17835]; Epigen-Epigenomics Flagship Project and AriSLA full grant 2014 'ARCI'. Work in GGT's lab  was supported by the  European Research Council  [ RIBOMY-LOME 309545 ];  Spanish Ministry of Economy and Competitiveness  [ BFU2014-55054-P ]. The  RAINET  project leading to this publication has received funding from  Excellence Initiative of Aix-Marseille University --A*MIDEX, Nucleic Acids Research, 2018, Vol. 46, No. 2 927 a  French 'Investissements d'Avenir' programme  (to C. B. ). Funding for open access charge:  Excellence Initiative of Aix-Marseille University --A*MIDEX [RAINET].
Background: The Strengthening and Stretching for Rheumatoid Arthritis of the Hand (SARAH) is a tailored, progressive exercise program for people having difficulties with wrist and hand function due to rheumatoid arthritis (RA). The program was evaluated in a large-scale clinical trial and was found to improve hand function, was safe to deliver, and was cost-effective. These findings led to the SARAH program being recommended in the UK National Institute for Health and Care Excellence guidelines for the management of adults with RA. To facilitate the uptake of this evidence-based program by clinicians, we proposed a Web-based training program for SARAH (iSARAH) to educate and train physiotherapists and occupational therapists on delivering the SARAH program in their practice. The overall iSARAH implementation project was guided by the 5 phases of the analysis, design, development, implementation, and evaluation (ADDIE) system design model.
Objective: The objective of our study was to conduct the first 3 phases of the model in the development of the iSARAH project. Methods: Following publication of the trial, the SARAH program materials were made available to therapists to download from the trial website for use in clinical practice. A total of 35 therapists who downloaded these materials completed an online survey to provide feedback on practice trends in prescribing hand exercises for people with RA, perceived barriers and facilitators to using the SARAH program in clinical practice, and their preferences for the content and Web features of iSARAH. The development and design of iSARAH were further guided by a team of multidisciplinary health professionals (n=17) who took part in a half-day development meeting. We developed the preliminary version of iSARAH and tested it among therapists (n=10) to identify and rectify usability issues and to produce the final version.
We, therefore, proposed a free Web-based training program for SARAH, iSARAH  [13] , to serve this purpose. Web-based training programs use modern telecommunication and information technologies to deliver information and have the capacity to accommodate multimodal learning formats (eg, written materials, multimedia, animations, feedback, and assessments)  [14, 15]. They can reach many people at their convenience, can overcome geographical barriers, and are cost-effective in terms of time, effort, and travel  [15]. Web-based training has the potential to be an effective method of reaching and training health professionals globally  [16] [17] [18] [19] [20]. The iSARAH implementation project is based on the analysis, design, development, implementation, and evaluation (ADDIE) model, one of the common instructional system design models used for constructing Web-based programs  [21] [22] [23] [24].
The analysis stage comprises defining the problem, identifying the target knowledge users, and looking for possible solutions to bridge the knowledge-action gap and user-specific needs for the dissemination tool. In the context of the SARAH program, the knowledge-action gap is the evidence-based SARAH program (current knowledge) and its application in practice (action). The targeted users are the physiotherapists and occupational therapists who routinely treat and prescribe hand exercises to people with RA. We proposed to bridge the knowledge-action gap by educating and training the therapists on the SARAH program with a knowledge dissemination tool (iSARAH). The design stage consists of finding ways to organize and present the content, identifying modes of delivery, and developing an evaluation plan of the dissemination tool.
This stage involves conceptualizing and adapting the SARAH program to fit the Web-based iSARAH. The development stage involves building iSARAH, evaluating its usability issues, and refining iSARAH to develop the final version. The implementation stage involves making iSARAH available for NHS therapists. The evaluation stage will include evaluation of learning outcomes such as knowledge, attitudes, intention to implement and user satisfaction with iSARAH, and evaluation of actual use of the SARAH program by iSARAH-trained therapists in real-world settings. Here we describe the first 3 phases of the iSARAH implementation project.
Phase 1: iSARAH Needs Analysis Specific objectives of this phase were (1) to explore routine exercise prescription practices and outcomes use among therapists who treat people with RA affecting the hands and wrists, (2) to identify barriers and facilitators to implementing the SARAH program, and (3) to collect therapists' opinions and preferences on the design, content, and features of iSARAH. A convenience sample of physiotherapists and occupational therapists of different countries who downloaded the SARAH program materials from the OCTRU website and gave permission to be contacted by the SARAH team were considered eligible for participation in the SARAH survey. Willingness to provide consent for taking part in the survey was the other inclusion criterion. We developed a survey questionnaire (Multimedia Appendix 1) that focused on routine therapist practice patterns in prescribing hand exercises for people with RA, and their experiences of using the SARAH program in clinical practice since they downloaded the SARAH program materials.
Phase 2: iSARAH Design Specific objectives of this phase were (1) to design a paper prototype of iSARAH, and (2) to gain feedback from a multidisciplinary group of health professionals and to agree on the content, delivery methods, frequently asked questions (FAQs), and the navigation, layout, and visual appeal features of iSARAH. The SARAH research team and information technology experts mapped the SARAH program from the SARAH clinical trial to a 3-to 4-hour Web-based training package for therapists and designed a paper prototype. We proposed a half-day meeting with rheumatology clinicians, researchers, and technology experts based on their convenience and availability to attend the meeting. The purpose of this meeting was to gain collective feedback on the prototype and the survey findings to finalize the design of iSARAH.
Self-Reported Questionnaires We used the Computer System Usability Questionnaire (CSUQ)  [29]  to evaluate user satisfaction, ease of use, information, and interface of the program on a 7-point Likert scale (1=strongly disagree to 7=strongly agree). We measured iSARAH usefulness on a 5-point Likert scale (1=not at all useful, 2=slightly useful, 3=moderately useful, 4=very useful, and 5=extremely useful). We measured overall ease of use on a 5-point Likert scale (1=very difficult, 2=somewhat difficult, 3=neither difficult nor easy, 4=somewhat easy, and 5=very easy). We measured confidence in using iSARAH on a 5-point Likert scale (1=not at all confident, 2=somewhat confident, 3=not sure, 4=confident, and 5=very confident).
Phase 2: iSARAH Design Following the multidisciplinary team meeting, we identified the specific need to educate and train therapists on the behavioral support strategies and proposed a separate module on this topic. We agreed that a section addressing common questions that might be raised by therapists about the SARAH program in real-world settings should be included in an FAQ section of iSARAH. Attendees provided suggestions for framing these questions. Based on discussions about the iSARAH prototype and SARAH survey findings, the team suggested the following recommendations: (1) to provide weblinks within the text for additional information on a topic, for example, Splints in RA, (2) to provide a progression status bar to enable users to know where they are in the training, (3) to use consistent names for exercises, (4) to have a separate educational video on joint protection advice,  (5)  to have a separate module on behavioral support strategies,  (6)  to have SARAH exercises demonstrated through videos and photographs,  (7)  to have brief modules,  (8)  to have a plain layout and use optimal font sizes (14 point),  (9)  to have an official email support to address technical enquiries, and  (10)  to ensure iSARAH adapts across different types of Internet browsers and computers at NHS settings and other telecommunication devices.
Specific recommendations were also made regarding the behavioral strategies module:  (1)  to provide examples of general goals relating to upper limb function to aid therapists with goal setting, and (2) to include model scenarios on filling in the personal exercise guide and Barriers and Facilitators form. 1. Make it clear in iSARAH that the SARAH program is flexible and will be feasible to complete at the user's convenience. 2. Send monthly email reminders to iSARAH-trained therapists. 3. Signpost therapists and their patients to resources needed to deliver the program, which could, ideally, be purchased at a discounted rate (eg, therapeutic putty, resistance bands). 4. Provide multiple hard copies of the SARAH patient materials at no cost to iSARAH-trained therapists for use in clinical practice, if required.
5. Demonstrate high credibility by incorporating information about the SARAH research team and all SARAH peer-reviewed publications. 6. Propose pain and self-reported hand function as the main outcomes for the evaluation phase. To facilitate effective implementation of the SARAH program by iSARAH-trained therapists in actual practice, we also discussed ways to minimize major implementation barriers reported in the survey (time limitations, forgetting, and difficulties in access to and cost of SARAH exercise equipment and patient materials). Clinicians who had worked on the SARAH clinical trial raised some issues with the original forms used in the trial, and they proposed ways to streamline these forms to make them easier to use.
Think-Aloud Procedure One of the major usability issues we observed was the difficulty in navigating from the end of one module to the next (eg, from the last page of Module 1 to the first page of Module 2), as there were no direct buttons to take users to the following module. Instead, participants had to click the respective module tabs on the top of the screen to navigate between modules or to proceed to the next module. We also noticed that some additional tabs appearing within the Moodle platform were confusing for the participants. Hyperlinks to reference documents such as SARAH trial publications and patient materials were reported to be repetitive and distracting. Participants said that photographs showing RA hands and activities of daily living, and other illustrations, did not add to iSARAH but instead occupied screen space and led them to frequently scrolling down to read the whole page.
Modifications Made to Produce the Final Version of iSARAH We revised iSARAH to address all major usability issues identified from the think-aloud procedure and interviews (Table  5 ). We produced good-quality promotional (Multimedia Appendix 2) and instructional videos using media professionals and removed all irrelevant photographs to allow more screen space. We minimized repetitive links to reference documents and patient materials within modules. We set up clear-cut tabs to navigate between the end of a module and the start of subsequent modules. The SARAH implementation team further reviewed the final version of iSARAH (Multimedia Appendix 3) for content, navigation issues, and grammar. Prior to official launch on April 3, 2017, we tested and activated the following features: (1) online user registration page, (2) online feedback questionnaire on perceived usefulness, satisfaction, and intention to use the SARAH program in future practice, and (3) download option for the training completion certificate.
Solutions implemented in the final iSARAH a Usability issues Navigation was made easy by adding buttons to take the user from the last page of the previous module to the first page of next module. Navigation between the last and first pages of consecutive modules was difficult. Only 2 colors were used: black for text and blue for weblinks. Different-colored text was hard to follow. Sections A, B, and C of Module 2 were categorized as separate modules: modules 2, 3, and 4. Sections A, B, and C of Module 2 were confusing. FAQs and self-assessment were labelled with their same names for more clarity. Having FAQs b and self-assessment labelled as modules was irrelevant. Documents were set to easily open up and close in a separate window that will allow users stay on their last seen page of the training.
A promo video was produced. The home page did not cover all essential information about the SARAH c program and SARAH team. All irrelevant buttons and tags were removed. Some Moodle features (eg, tags, buttons) were distracting. Good-quality videos were produced. The quality of videos could be improved. Exercise videos with a patient volunteer demonstrating the exercises were produced. A patient could demonstrate exercises in exercise videos. The text was reduced, and more bullet points were used. There was too much text to read.
Principal Findings Engagement with users through the SARAH survey allowed us to identify current practice and learning needs to ensure iSARAH was fit for purpose. From the survey, we established that the exercises included in the SARAH program were commonly used by therapists  [6, 7, 30, 31]  but the behavioral change techniques were likely to be less familiar  [8] [9] [10]. It also gave us insight into potential barriers to implementation. Respondents provided information about the features they would like to see in a Web-based training program, and this directly informed the design of the program. Survey findings also directly influenced the selection of outcomes for the evaluation phase of implementation. Engagement with users continued during the design phase with a face-to-face meeting, as well as carrying out usability testing.
Usability testing was essential to producing a user-friendly website that could be deployed for implementation. We believe this has resulted in a flexible learning experience for users, which is easy to navigate with unlimited access. We included FAQs and self-assessment to ensure that therapists have adequate training and skills to efficiently apply for the SARAH program in actual practice. The next step is to evaluate the impact of iSARAH training on actual implementation of the SARAH program, including the impact on knowledge and skills of therapists, implementation rates, and patient outcomes. We know from our previous work  [32]  that training alone may not result in implementation  [33]. A Web-based training developed to facilitate the implementation of a cognitive behavior approach for low back pain was shown to be as effective as face-to-face training regarding knowledge and confidence, but actual implementation rates were low and further enhancement of the training was required  [33].
Limitations This study has some limitations. First, we neither used observational analysis with video recordings in the think-aloud procedure to observe users' interactions with iSARAH, nor conducted a systematic qualitative analysis of participants' interviews. Second, the CSUQ and Likert scales have not been tested for reliability and validity in the target population. Hence, the range of scores should be interpreted with caution. Third, the SARAH survey participants were familiar with the SARAH program and hence their responses were prone to the risk of volunteer bias. Additionally, with a low consent rate (39 of 102 participants, 38. 2%), the survey findings are at the risk of nonresponse bias from people who did not participate or respond. Fourth, we did not employ iterative cycles of usability testing-that is, consecutive cycles of testing until the point when no further usability issues were identified-but we used the feedback from all participants in a one-off cycle to refine iSARAH.