dataesr/scientific-paragraphs-categorization huggingface dataset:
Normalization of reads counts over transcripts was carried out using the upper-quartile method option of edgeR  [79]. Only transcripts showing a normalized count value per millions (cpm) of 1, in at least two samples were considered for further analyses. The edgeR package  [79]  was used to analyze differential expression following a glm approach  [79]. Sexual samples were established as controls, therefore positive values of logFC were associated to an increased number of sRNA reads in apomictic libraries and negative values indicated an increased number of sRNA reads in sexual libraries. Read coverage comparison resulting in an adjusted p-value < 0. 05 (FDR)  [80]. Comparisons producing FDR < 0. 05 and fold changes in the range of 1-2 and > 2 were considered as moderate and high coverage differences, respectively.
Then, candidate cluster (i. e. genome/transcriptome-wide regions containing small RNAs accumulation) associated to small RNA sequences were identified with the default parameters. Putative miRNAs were then selected based on a DicerCall of 20-22. Mature miRNA sequences were compared against miRBase  [48]  using the SSEARCH option and a cut off E-value < 0. 05 to detect conserved miRNAs. Mature sequences that produced no hit were considered as putative new P. notatum miRNAs (Pn_miRNAs). The secondary structure of the predicted novel miRNA genes was analyzed using RNAfold within the ViennaRNA Package  [82]  and manually examined for the presence of putative mature miRNA sequences in one arm of the stem region, bulges with no more than 3 unpaired nucleotides, a loop of at least 10 nucleotides in length and free-folding energy lower than or equal to -60 kcal mol -1  [83].
Identification of miRNA target transcripts in Paspalum and differential expression We used TargetFinder  [85]  with the default parameters and a cut off value of 4 to predict miRNAs targets expressed in the Paspalum reference transcriptome. Common ontologies (GO-Slim and PO) were established using the PANTHER  [86]  and Planteome  [45]. Finally, for differential expression of Paspalum targets between sexual and apomictic developments, we took advantage of former expression analysis, considering only those transcripts that showed at least 10 reads in one of the libraries  [24].
Acknowledgments Authors acknowledge to  Professor Camilo Quarin  from  IBONE  for providing the plant material used in this work. C. Azzaro  and  C. Colono  received fellowships from  CONICET ,  Argentina. J. P. A. Ortiz ,  L. Siena ,  M. Podio  and  S. Pessino  are research staff members of  CONICET, Argentina.
Availability of data and materials The datasets supporting the conclusions of this article are available in the NCBI Sequence Read Archive (SRA) repository under accession number SRP099144. Additional dataset(s) supporting the conclusions of this article are included within the article and its additional files. The plant materials used in this study belong to the living germplasm collection of Instituto de Botánica del Nordeste (IBONE), CONICET-UNNE, Corrientes, Argentina. Voucher specimens of this material are deposited at the Herbarium CTES-IBONE (publicly available), under deposition numbers: C4-4X (Quarin, C. L. 4260, barcode CTES0541627, cardboard No. 330064); Q4117 (Quarin, C. L. 4117, barcode CTES0541626, cardboard No. 233851).
Introduction: The Informed Health Choices (IHC) project has developed learning resources to teach primary school children (10 to 12-year-olds) to assess treatment claims and make informed health choices. The aim of our study is to explore both the students' and teachers' experience when using these resources in the context of Barcelona (Spain). Methods: During the 2019-2020 school year, we will conduct a pilot study with 4 th and 5 th -year primary school students (9 to 11-year-olds) from three schools in Barcelona. The intervention in the schools will include: 1) a workshop with the teachers, and 2) lessons to the students. The data collection will include: 1) initial assessment of the.
The study showed that the children who used the resources improved their ability to assess treatment claims in comparison with the group without resources (69% of the children who use the learning resources got a passing score vs. 27% of children in the control group)  9. A follow-up study one year later showed that children retained this knowledge and, in fact, the proportion of children with a passing score increased from 69% to 80%  16. Additionally, the IHC project team developed and evaluated a podcast with several episodes for parents (that introduce and explain nine key concepts)  8, 14, 17, 18. Tool to evaluate the ability to assess treatment claims. The IHC Working Group has created a database with questions to assess people's understanding and ability to apply the key concepts; the CLAIM Evaluation Tools 19.
Selection of the students and teachers. We will select 4 th and 5 th -year primary school students (9 to 11-year-olds) in all the lines from the selected schools (in this context, the number of lines means the number of student groups per academic level). We expect to include a convenience sample of approximately 150 students (25 students per class * two lines per school * three schools). We will request written informed consent from the families (Extended data 1 and 2)  24, 25. We will select one teacher from every 4 th or 5 th year class in the selected schools. We expect to include six teachers (one teacher per class * two lines per school * three schools). The profile of the participatory teachers, as well as the subject Group responsible for reviewing and advising during the development of the different steps of the pilot study.
Workshop with the teachers The objective is to introduce and review the IHC project, the pilot study, and the IHC resources with the teachers. Before the workshop, a paper copy of the resources translated into Spanish will be sent to the teachers for their review. During the workshop, a researcher from the IHC-Barcelona Working Group will introduce the IHC project and the pilot study. In addition, a mock lesson will be taught as an example (previously selected by the teachers). Finally, a teacher from each school will explain the plan to teach the lessons to the student body. The workshop will last approximately five and a half hours (Table  3 ; Extended data 4)  27.
Initial assessment of the resources by the teachers The objective is to explore the teachers' initial perception of the IHC resources. We will explore the teachers' initial perception of the IHC resources using an ad hoc self-administered questionnaire after the workshop. The questionnaire will include: teacher's impression of the students' expected experience with the IHC resources (understandability, desirability, suitability, and usefulness), the teachers' experience with the IHC resources (understandability, desirability, suitability, and usefulness), examples of treatment claims, and comments (Table  3 ; Extended data 5)  28.
Non-participatory observations during the lessons The objectives are to assess (objectively) the degree of implementation of the IHC resources and explore the students' experience when using the IHC resources. A researcher from the IHC-Barcelona Working Group will make the non-participatory observations during the lessons. For convenience, each lesson will be observed in two classes (18 observations). Which lesson is going to be observed in each class will be assigned randomly. The researcher will record his or her observations in an ad hoc guide that will include: researcher's impression of the students' and teachers' experience with the IHC resources (understandability, desirability, suitability, and usefulness), technique used to teach the lesson, the facilitators and barriers to teach the lesson, examples of treatment claims, questions, and comments (Table  3 ; Extended data 6)  29.
Semi-structured interviews with the students after a lesson The objective is to explore the students' experience when using the IHC resources. A researcher from the IHC-Barcelona Working Group will hold, with the support of a teacher, semi-structured individual interviews with a selection of students after a lesson. For convenience, two interviews will be held per lesson (18 interviews). Which student is going to be interviewed in each class will be assigned randomly (using the alphabetical attendance sheet). In the event that any of the selected students does not wish to participate, the next student will be selected from the list. Each interview will last approximately 30 minutes, and its audio will be recorded and transcribed. The researcher will hold the semi-structured interview using an ad hoc guide that will include: the students' experience with the IHC resources (understandability, desirability, suitability, and usefulness), examples of treatment claims, suggestions to improve the lesson, questions, and comments (Table  3 , Extended data 7)  30.
Assessment of the lessons by the teachers The objectives are to assess (self-reportedly) the degree of implementation of the IHC resources and explore the teachers' experience when using the resources. After teaching each lesson, the teachers will assess it in an ad hoc self-administered questionnaire. The questionnaire will include: teacher's impression of the students' experience with the lesson (understandability, desirability, suitability, and usefulness), the teachers' experience with the lesson (understandability, desirability, suitability, and usefulness), the technique used to teach the lesson, the facilitators and barriers to teach the lesson, suggestions to improve the lesson, questions, and comments (Table  3 , Extended data 8)  31.
Final assessment of the resources by the teachers The objectives are to explore the teachers' final experience when using the IHC resources and compare their initial perception with the final experience. After completing all the lessons, we will explore the teachers' final experience with the IHC resources using an ad hoc self-administered questionnaire. The questionnaire will include: teacher's impression of the students' experience with the IHC resources (understandability, desirability, suitability, and usefulness), the teachers' experience with the IHC resources (understandability, desirability, suitability, and usefulness), and comments (Table  3 ; Extended data 9)  32.
However, we will provide a detailed description of our data collection and research context to help other stakeholders consider transferring our results to their settings. ". To evaluate implementation considerations, we would have to conduct a context analysis [IHC 2020]. The mail objectives of a context analysis would be: 1) explore what demand there is for learning resources for teaching critical thinking about health in schools, 2) map where teaching critical thinking about health best fits in the curriculum, 3) identify and examine relevant resources already in use, and 4) explore conditions for introducing new learning resources [IHC 2020]. The development of context analysis in our setting is already considered in the "Discussion -Implications for practice and research" section, the text reads: "The next contextualization activities will be: 1) content adaptation -if needed, 2) context analysis, and 3) validation of the CLAIM questionnaire test into Spanish for use in this context.
The Lancet. 2017; 390 (10092): 374-388 Publisher Full Text 4. WHO: Standards and operational guidance for ethics review of health-related research with human participants. Reference Source 5. Electronic Code of Federal Regulations, Part 46-Protection of Human Subjects. Reference Source 6. WHO: The WHO strategy onresearch for health. Reference Source 7. Pan American Health Organisation World Health Organisation 49th Directing Council and 61st Session of the Regional Committee of WHO. Reference Source Is the rationale for, and objectives of, the study clearly described? Partly Is the study design appropriate for the research question? Partly Are sufficient details of the methods provided to allow replication by others? Partly Are the datasets clearly presented in a useable and accessible format? Not applicable.
○ I would consider TIDier Checklist to better describe intervention details. ○ I would describe the time points for each of the outcome measures. ○ Data analysis -'qualitative' variables should be replaced by 'categorical' and 'quantitative' variables by 'continuous' -Both quantitative measures. ○ Authors should describe whether the resources have been translated and validated into Spanish. Is the rationale for, and objectives of, the study clearly described? Yes Is the study design appropriate for the research question? Yes Are sufficient details of the methods provided to allow replication by others? Partly Are the datasets clearly presented in a useable and accessible format? Not applicable Competing Interests: No competing interests were disclosed. Reviewer Expertise: Evidence-based practice I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.
Acknowledgements Laura Samsó Jofra  is a doctoral candidate at the  Paediatrics, Obstetrics and Gynaecology and Preventive Medicine Department, Universitat Autònoma de Barcelona, Barcelona, Spain. We would like to thank the three schools in Barcelona ( Escola Sant Martí ,  Escola Virolai  and  Institut Escola Antaviana)  for their participation in the pilot study. Additionally, we would like to thank  Escola Virolai  for their participation in the translation of the IHC resources into Spanish. We would like to thank  Dr Andrew Oxman  ( Centre for Informed Health Choices, Norwegian Institute of Public Health, Oslo, Norway ) for his advice and feedback on an earlier version of this protocol. Figure 2. Pilot study work plan.
LMG has a Miguel Servet research contract from the  Institute of Health Carlos III  [ CP18/00007 ]. Dr. Antoni Esteve Foundation  has funded the Spanish translation and production of the IHC resources. The funders have not participated in the pilot study design nor will they participate in its development. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The study protocol has obtained an approval exemption from the.
g. a number of students). ○ I would consider TIDier Checklist to better describe intervention details. ○ I would describe the time points for each of the outcome measures. ○ Data analysis -'qualitative' variables should be replaced by 'categorical' and 'quantitative' variables by 'continuous' -Both quantitative measures. ○ Authors should describe whether the resources have been translated and validated into Spanish. Is the rationale for, and objectives of, the study clearly described? Yes Is the study design appropriate for the research question? Yes Are sufficient details of the methods provided to allow replication by others? Partly Are the datasets clearly presented in a useable and accessible format? Not applicable Competing Interests: No competing interests were disclosed. Reviewer Expertise: Evidence-based practice I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.
Reference Source Open Peer Review Current Peer Review Status: Version 1 This is an open access peer review report distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Reviewer Report 26 March 2020 https://doi. org/10. 5256/f1000research. 23446. r61277 © 2020 Cuervo L et al.
R. Cervera (Barcelona, Spain) looked back at the start of the European Forum in 1996 that already resulted in more than 100 collaborative research projects. Characteristics of two large multicenter studies, the Euro-Phospholipid project and CAPS Registry, were reviewed. Finally, the PRECISESADS project was introduced, aiming to find clinically useful biomarkers based on data gathered from 2500 people with various autoimmune diseases concerning the molecular cause of their disease. H. Cohen (London, UK) presented an update on the RISAPS study, a randomized controlled phase 2/3 noninferiority trial testing rivaroxaban (15 mg twice daily) versus warfarin (target INR 3. 5) in 140 stroke patients with APS. Primary outcome (i. e. , rate of change in brain white matter hyperdensity between baseline, and 24 months follow-up) as well as key secondary outcomes (i.
The ERN aims to tackle complex/rare diseases requiring specialized treatment and concentration of knowledge. More specifically, ReCONNET, the ERN on connective tissue and musculoskeletal diseases, includes APS. The European Forum may help to assemble the most reliable database including all the information necessary for patient's management without being too time-consuming for clinicians. On the other hand, ReCONNET will provide a European Platform for the registry which will be disseminated to all health care providers. A. Mekinian (Paris, France) proposed a prospective and retrospective multicenter open-labeled study to evaluate obstetrical outcome and treatments during pregnancy in seronegative primary APS patients. Included patient samples are required to meet thrombotic and/or obstetrical primary clinical seronegative APS (Sydney criteria) and the presence of at least one non-conventional aPL.
The ex vivo association of aPL with platelet-bound C4d suggests the involvement of the classic complement pathway in the pathogenesis of APS. In vitro data support this hypothesis. In the presence of a second hit, β2GPI was able to bind to platelets, followed by aβ2GPI. The resulting immune complex then activates the complement, leading to C4d deposition. N. Sippl (Stockholm, Sweden) characterized β2GPI specific B cells from APS patients. The number of β2GPIspecific B cells, especially plasmablasts, was increased in APS patients. Of note, the VH gene usage showed a bias towards different V-regions depending on the isotype. Recombinant antibodies are currently being produced to further investigate the binding and pathogenic properties. T. Moulinet (Nancy, France) evaluated the predictive value of thrombocytopenia in APS.
To get more detailed structural information from the SAXS data, we applied the Ensemble Optimization Method (EOM). 26 The NMR analysis indicates that the presence of the two grafted ubiquitins does not perturb the conformational features of p15, which remains disordered in solution. Prompted by this observation, we have modeled the p15 protein as an IDP in both scenarios, with or without randomly oriented ubiquitin tags at residues 15 and 24. An atomistic ensemble model of the doubly monoubiquitinated p15 was built combining flexible-meccano (FM), molecular dynamics (MD) simulations, and in-house scripts (see methods for details). A second ensemble for p15CCSS was built by removing both ubiquitin moieties and the linkers from the dmUbp15 ensemble (Figure  4C ). Using these structural pools, the EOM-derived ensembles provided an excellent fit to the experimental SAXS curves of p15CCSS and dmUbp15, with χ i 2 values of 0.
ACS Chemical Biology Articles dmUbp15 Interacts with PCNA as Nonubiquitinated p15. The interaction of dmUbp15 with PCNA was studied by ITC and NMR. Calorimetry shows that one molecule of dmUbp15 binds to each protomer of PCNA with a K d of 1. 6 ± 0. 1 μM at 25 °C (Figure  S7  and Supplementary Table  S1 ), which is similar to the isolated p15, with a K d of 1. 1 ± 0. 1 μM 4. The mutation C54S, within the PCNA binding region of p15, does not affect the affinity (K d = 1. 3 ± 0. 1 μM, Figure  S7  and Table  S1 ). This result appears in contradiction with the previously reported promotion of PCNA binding by ubiquitination of p15 observed by nuclear colocalization. 6 ur quantitative calorimetry measurements demonstrate that ubiquitination does not affect the direct interaction between p15 and PCNA, and our NMR data shows that the PCNA binding mode of dmUbp15 is equivalent to that of p15 (Figure  2C ).
26, 36 he interest in IDPs has recently increased because of their involvement in the formation of membraneless organelles via protein phase separation. 37 Solutions of p15 or dmUbp15, however, do not show phase separation (at least up to 20 g/L at 25 °C), and our SEC-MALS data demonstrate that both are monomeric. Both proteins are intrinsically disordered, as confirmed by NMR. In the case of isolated p15, residual dipolar couplings showed the existence of low populations of nonrandom conformations in certain regions of the chain that could not be identified by local chemical shift deviation. 14 ossibly, dmUbp15 also shows some preferential local conformations, but these have too low populations for detection by chemical shift analysis (Figure  3 ). Ubiquitination causes only local perturbations in p15 chemical shifts and backbone dynamics, as sampled via  15  N NMR relaxation.
The column was equilibrated with 0. 1 μm filtered PBS (10 mM phosphate, 140 mM chloride, 153 mM sodium, 4. 5 mM potassium) at pH 7. 0, and the SEC-MALS system was calibrated with a sample of bovine serum albumin (BSA) at 1 g/L in the same buffer. Next, 0. 1 mL of dmUbp15 protein at 1 g/L was injected at 0. 5 mL/min. The data was acquired and analyzed by ASTRA (Wyatt). From repeated measurements of BSA samples at 1 g/L under identical or similar conditions we estimate an experimental error of ca. 5% in the molar mass. CD Spectroscopy. Spectra of 3 μM dmUbp15 or p15CCSS samples in PBS pH 7. 0 were recorded on a Jasco-815 spectropolarimeter at 25 °C in a quartz cuvette (path length 2 mm). NMR Spectroscopy. All NMR experiments were recorded at 35 °C (for observation of PCNA) and 25 °C (for observation of dmUbp15 or free ubiquitin) on a Bruker Avance III spectrometer operating at 18.
The system was equilibrated for 0. 2 ns in the NVT ensemble and then for another 0. 2 ns in the NPT ensemble with a 2 fs time-step. The production MD run spanned 14 ns, and from the last 10 ns, a frame was extracted every 10 ps to create a library of 1 000 different linker positions. From this library, the two engineered cysteine residues of each p15CCSS structure were labeled in silico with one randomly selected and sterically allowed linker conformation, followed by grafting an ubiquitin-moiety (PDB: 1UBQ), with flexible C-terminal residues 74-76, onto the amino group of the attached linker (i. e. , Ub-Gly76-CO-NH-CH 2 -CH 2 -S-S-CH 2 -Cys15/24-p15), resulting in 12 000 doubly ubiquitinated p15 (dmUbp15) conformers with no steric clashes. To obtain the equivalent pool of p15CCSS conformers, we removed the linkers and the Ub-tags, so that each dmUbp15 conformer had its untagged version.
Isothermal Titration Calorimetry. For dmUbp15 binding to PCNA, we employed a Microcal iTC200 calorimeter with 25 μM PCNA in the cell at 25 °C. The PCNA protein solution (dialyzed against PBS, pH 7. 0) was titrated with a 0. 4 mM stock solution of dmUbp15 prepared by dissolving the lyophilized material in the dialysis buffer and adjusting the pH to 7. 0 with NaOH. For binding to p15CCSS and p15C54S, PCNA was dialyzed against PBS pH 7. 0, 2 mM TCEP. PCNA 20 μM solutions in the cell were titrated with 400 μM of the corresponding p15 variant. The binding isotherms were analyzed by nonlinear least-squares fitting of the experimental data to a model assuming a single set of equivalent sites,  56  using Microcal Origin (OriginLab). For experiments with the RFTS domain of Dnmt1, we used a Microcal PEAQ-ITC (Malvern) calorimetry system.