dataesr/scientific-paragraphs-categorization huggingface dataset:
Stage 2. 1 data analysis Data analysis of the seminal and lower quality metaethnographies will focus on what and how the authors of each meta-ethnography conducted and reported each phase of a meta-ethnography, especially the analysis phases 4 to 6. We will identify the range of approaches, compare and contrast their approaches with recommendations and guidance identified from the methodological texts in Stage 1, identify any examples of how seminal texts have advanced the meta-ethnography method, and define good and poor reporting practices. Characteristics of the meta-ethnographies will be recorded including the authors, title, journal details including article word limits, publication year, the main topic focus, aim of the review, and the number of studies synthesised. For rigour and to enhance richness of interpretation, four members of the project team with meta-ethnography expertise will contribute to data analysis.
The content of telephone interviews with professional end users will be documented via detailed note-taking and the issues collated to identify what represents good reporting to them. Included meta-ethnography texts will be qualitatively analysed deductively and inductively. The initial deductive coding frame of analytic categories will be based on the typology identified in Stage 1 and will be refined as new codes are developed inductively from the data and from interviews with professional end users. The suitability of the approach for the study aim, the rationale for the use of meta-ethnography, how each phase in the metaethnography was conducted and reported, and good practice in any area of doing or reporting a meta-ethnography are topics likely to be analysed. The analysis of the usefulness of and the actual practice in the seminal and lower quality meta-ethnographies will be juxtaposed with the recommendations and guidance from Stage 1 to identify commonalities and differences.
Stage 2. 2 Audit of published meta-ethnographies The literature will be audited to examine how published meta-ethnographies perform against the standards developed from the good practice principles identified in stage 2. 1 and to further develop these principles and standards. Database searches will be conducted to identify published, peer-reviewed, health-related or social care meta-ethnography journal articles published since 1994. No peer-reviewed, health-related meta-ethnography journal articles were published before 1994  (10). The aim is to identify a broad range of meta-ethnographies from which to purposively sample articles. Electronic databases will be searched including: MEDLINE, PsycARTICLES, PsycINFO via Health Source: Nursing/Academic Edition; Pubmed; the International Bibliography of the Social Sciences; Sociological abstracts; Applied Social Sciences Index and Abstracts; and CINAHL.
Stage 2. 2 data analysis Characteristics of the meta-ethnographies, e. g. , title and authors, will be recorded in the same bespoke template that will be developed and used in Stage 2. 1. Data will be extracted from included texts into a coding frame based on the draft standards and will be analysed qualitatively to judge if they meet the standards identified in Stage 2. 1. The coding frame will be revised to allow for refinement of and additions to the principles and standards as new codes are developed inductively from the data. A detailed analysis will be produced comparing the conduct and reporting in recent meta-ethnographies to the standards to see whether and how they follow good practice, to identify any additional good practices, and identify examples of how the method has been further advanced, for example, in how the analysis processes are reported.
Data collection and analysis Presentations will be followed by open debate, questions, brainstorm, exchanges of views and knowledge, and discussion  [32]. The definition of a meta-ethnography, how close standards and items are to best practice, and whether further improvement is needed will be explored. Comments will be solicited from other stakeholders on the utility of meta-ethnography reports for improving clinical practice and intervention implementation. Participants will have the opportunity to suggest further guideline standards and items for inclusion in the eDelphi studies, identify and combine duplicative standards/ items, and revise the wording of items. Panel members' feedback on the proposed standards and items for the guideline will be systematically recorded and thematically analysed, noting if they are an academic expert or other stakeholder.
This web-based platform has automatic reminders, collation, analysis and feedback functions which considerably increase efficiency by reducing the administration and manual analysis that is normally required between Delphi study rounds. Rates of study participation are comparable to paper-based administration methods  [39]. Upon logging in to the eDelphi website, the participant is presented with the questionnaire. In rounds 2 and 3 the participant sees the same items they rated in the previous round plus any additional items subsequently suggested by participants. They also see the most popular response (s) to each item from the previous round, their own previous response, and the relative frequency of responses for each item. These data are presented visually in the form of a colour histogram or 'heat map' which overcomes some of the known limitations of using measures of central tendency  [41]  when feeding back results to participants, e.
Data collection Data collection will take 12 weeks in total and takes place over three rounds, each lasting four weeks. Having three rounds avoids excessive participant fatigue and maximises the potential to reach consensus amongst participants  [41]. Electronic reminders will be sent automatically to participants two weeks after the commencement of each round, and also shortly before the end of the round to individuals who have not yet completed the round. These reminders state the final date by which the current round must be completed. In each round a set of provisional items (agreed in Stage 3. 1) will be presented on the eDelphi website. Each participant will be asked to rate how important they consider it to be (on a four point Likert-type scale from very important to very unimportant) that the item should appear in the guideline.
To be effective, a reporting guideline must be used. For this to happen, the intended users of the reporting guideline must be aware of the existence, and must trust in the quality, of the guideline and how it was developed. To engender trust in the guideline, it will be created through a rigorous study that follows good practice in reporting guideline development. The content of the guideline will be the culmination of learning from comprehensive literature reviews and debate with and the consensus of academic experts and other stakeholders. The project team will ensure that an audit trail of decisions made at each stage in the study is documented so that the decisionmaking process can be scrutinised. To raise awareness of the existence of the guideline we have registered our intent to produce these, and will register the final guideline, with the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) international network and comprehensive database of reporting guidelines (http:// www.
equator-network. org/). The project has also been awarded DECIPHer (Development and Evaluation of Complex Interventions for Public Health Improvement) affiliated status and the team will report project performance and impact to them annually. The methodological systematic review to be conducted in Stage 1 has been registered with the PROSPERO international database (http:// www. crd. york. ac. uk/PROSPERO/). Furthermore, we will negotiate with and ask editors of journals that publish meta-ethnographies to promote the guideline by making a clear statement of how the journal expects authors to use the guideline, what level of adherence is required, to consider asking authors to state how their article meets the guideline items and by asking peer-reviewers to use them as part of their review.
Acknowledgements This research protocol has been peer-reviewed by the  NIHR. The study has been awarded a project grant (grant number  13/114/60 ) under the  NIHR's Health Services and Delivery Research (HS&DR) Programme. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the  HS&DR Programme ,  NIHR ,  NHS  or the  Department of Health. The systematic reviews will be undertaken with the support of  DECIPHer , a  UKCRC   Public Health Research: Centre of Excellence. Funding from the  British Heart Foundation ,  Cancer Research UK ,  Economic and Social Research Council  ( RES-590-28-0005 ),  Medical Research Council , the  Welsh Government  and the  Wellcome Trust  ( WT087640MA ), under the auspices of the  UK Clinical Research Collaboration , is gratefully acknowledged.
mp. 13 Publishing/st [Standards] 14 methods/st 15 11 or 12 or 13 or 14 16 10 and 15 When searching bibliogrpahic databases 'wildcards' are used in a search query to represent unknown characters. In MEDLINE, the asterisk (*) represents any group of characters, including no character and a question mark (?) represents any single character, e. g. 'meta synthes?s' will find 'meta syntheses' and 'meta synthesis. '.
Background: Hereditary Fibrosing Poikiloderma (HFP) with tendon contractures, myopathy and pulmonary fibrosis (POIKTMP [MIM 615704]) is a very recently described entity of syndromic inherited poikiloderma. Previously by using whole exome sequencing in five families, we identified the causative gene, FAM111B (NM_198947. 3), the function of which is still unknown. Our objective in this study was to better define the specific features of POIKTMP through a larger series of patients. Methods: Clinical and molecular data of two families and eight independent sporadic cases, including six new cases, were collected.
Demographic data Fifteen patients belonging to 10 independent families were diagnosed with POIKTMP (Table  1 ). A mutation in the FAM111B gene was identified in all the patients tested. Six were females and nine were males. They were of French, Algerian, Irish, Italian, Moroccan, Dominican Republic and South-African origins. The median age at last follow-up was 20. 5 years (min = 8 months; max = 56 years).
Haematological abnormalities Eosinophilia was observed in three patients (individuals F1, F4 and F6). Individual F7 had a mild We identified a causative mutation in each family of the series. The variants consist of five different missense mutations that are predicted to localize in the trypsin-like cysteine/serine peptidase domain of the protein (Fig. 5 ) and are absent from all public genetic variant databases tested (dbSNP142 (http://www. ncbi. nlm. and c. 1883G > A (p. Ser628Asn). The last variant identified in individual F9 is located upstream of the loop, but still in the trypsin-like cysteine/serine peptidase domain (c. 1289A > C (p. Gln430Pro)). Mutations reported in POIKTMP are available in the LOVD variant database dedicated to FAM111B (www. LOVD. nl/FAM111B).
Acknowledgements We thank all the families who participated in this study. We are very grateful to all the collaborators who also contributed to this work:  Nasreddine Benchick ,  Claire Bénéteau ,  Catherine Bodemer ,  Jean-Benoit Courcet ,  Isabelle Desguerre ,  Solange Duriez ,  Sylvie Fraitag ,  Jérôme Franques ,  Jocelyne Havard ,  Darren Houniet ,  Bernard Keavney ,  France Leturcq ,  Laëtitia de Peufeilhoux ,  Olivier Pichon ,  Gasnat Shaboodien  and  Marc Tardieu , as well as  Réjane Troudet  and  Céline Chevrier. We thank  Neil Wilson  for technical assistance and  Christian Cole  for bioinformatics support.
pgtb. u-bordeaux2. fr) using the Illumina MiSeq version 2 sequencer and by combining mate-pair and paired-end libraries. De novo assembly was performed at the Bordeaux Bioinformatics Center (http://www. cbib. u-bordeaux2. fr/) using CLC and ABySS softwares. Coding sequences (CDSs) were predicted with the fully automated Rapid Annotations using Subsystems Technology (RAST) server (3). This initial annotation was improved by manual curation. The RNAmmer 2. 1 software (4) was run to verify rRNAs, and the Aragorn software (5) was used to predict tRNAs and transfer-messenger RNAs (tmRNAs). The annotated genome was integrated into the MolliGen database (http://cbi. labri. fr /outils/molligen/), which is dedicated to the comparative genomics of Mollicutes genomes  (6). Analysis of the M. meleagridis genome was supported by tools available in RAST/SEED and MolliGen.
Analysis of the M. meleagridis genome revealed that the arginine dihydrolase pathway is complete. Indeed, the genes arcA, arcB, and arcC encoding arginine deiminase (MMELEA_04580), ornithine carbamoyltransferase (MMELEA_04570), and carbamate kinase (MMELEA_04560), respectively, were identified. This finding is in accordance with the ability of M. meleagridis to alkalinize culture medium containing arginine  (9). This is the first genome sequence of the M. meleagridis species, which will be helpful for a better understanding of the genetic basis of the virulence of the pathogen. Further genome sequencing of M. meleagridis strains isolated from chickens will be necessary to address the question of host specificity. Nucleotide sequence accession numbers. This whole-genome shotgun project has been deposited at DDBJ/EMBL/GenBank under the accession no.
The most commonly studied aspects include MAPT haplotypes and Tau RNA splicing because of their involvement in certain tauopathies (for examples, see reviews  [57] [58] [59] [60] [61] ). Research regarding the epigenetic regulation of Tau expression is increasing. However, some aspects of Tau gene expression, such as the possible existence of different promoters and the potential role of the repeated motifs found in all MAPT sequences, have rarely been studied, despite the availability of abundant data in bioinformatics databases. The aim of this review is to provide a global synthesis of knowledge regarding the regulation of human MAPT gene expression at the DNA and RNA levels by evaluating data from the literature and bioinformatics databases. Several aspects will be discussed, including repeated motifs, CpG island/methylation, and haplotypes at the DNA level as well as the key regions involved in mRNA expression and stability (i.
Transposon-type repeats Transposon-type repeats can be classified into the following four categories: short interspersed nuclear elements (SINEs), long interspersed nuclear elements (LINEs), DNA transposons, and transposable elements with long terminal repeats (LTRs). All 4 categories of this type of repeat are found in the MAPT gene. Generally, SINEs are the most numerous, and among them, Alu sequences are the most frequent. Alu elements are 300-nucleotide (nt) sequences that occupy over 10 % of the human genome. These sequences contribute to genomic instability by eliciting gene mutations, altered gene expression and transcript splicing or by generating a new gene segment  [62]. Among the 83 Alu sequences identified in the MAPT gene using the TranspoGene database  [63] , 56 are on the sense strand and 27 are on the antisense strand.
For example, DM and Huntington's disease involve an RNA and protein, respectively, with a toxic gain of function (reviewed in  [68, 69] ). SSRs can be found throughout the MAPT gene using the Tandem Repeats Finder program (TRF/UCSC)  [70]. Interestingly, the first genetic marker identified as overrepresented in PSP patients was a dinucleotide repeat (11xTG, named TG 11 ) downstream of exon 9 (  [71, 72] , reviewed in  [60] ). Some of these repeats are clearly distinguishable based on the following features: (i) their repeat length (4 sequences are longer than 20 nt, and the longest sequence is 58 nt); (ii) their localization throughout the gene (shorter sequences of less than 20 nt are located before exon E4, whereas the longest sequence, which is more than 20 nt long, is located after E4); (iii) their proximity to alternative exons; and (iv) the repeat lengths of certain imperfect repeats, such as those of the dinucleotides TA or GT in intron 0 (TA 356, GT 187 ) (Fig.
CpG islands As determined by CpG Islands Track Settings (UCSC), one long CpG island spans approximately 300 nt upstream to 3000 nt downstream of E0 in human MAPT (the total [G + C] increases to 75 % around the transcription start site, with as high as 10 % CpG dimers)  [76] [77] [78]. This CpG island (CpG 300 ) is located in the promoter region (Fig. 1 , Fig. 2 ). Two additional but more limited sequences are present, including one containing 27 CpGs (CpG 27 ) that is located 13 kb upstream of E1 and another containing 21 CpGs (CpG 21 ) that is located immediately upstream of E4A (UCSC Genome Browser  [79] ). The CpG 21 island is situated at the beginning of the short transcript MAP-010/ENST00000576238 (Fig. 1 , Fig. 4b ). Thus, we cannot ignore the possibility that this CpG island may be involved in the transcriptional regulation of this minor transcript (see section 3.
2  Organization of the rat, mouse and human Tau promoters. The lengths of the various regions of the promoter are not representative of their precise localizations but are dependent on the cloning technique. Thus, differences in the length of a determined region among species are not significant. Note the influence of allelic variants on promoter activity. CpG islands present in the promoter are indicated Fig. 3  Transcription initiation sites (black perpendicular arrow) and termination sites (simple gray arrow). These sites enable the expression of the complete Tau transcript/protein. For other sites, see Fig. 4b. Red numbers: initiation sites according to the database. Green numbers: initiation sites described in  [77]. FS: forward strand, RS: reverse strand to microdeletion/microduplication/microtriplication of this short genomic region  [29] [30] [31] [32].
The first exon is generally named exon 0 (E0) in the literature, and exon 4A corresponds to the alternative exon located between exons 4 and 5. The exon numbers provided in the databases must be carefully considered when determining the functions of analyzed transcripts because different exons may be assigned the same number depending on the transcript analyzed. Three Tau transcripts of 2 kb, 6 kb, and 9 kb in length are encoded by the MAPT gene (reviewed in  [57] ). These transcripts differ from one another by their splicing patterns, as demonstrated by the differences between the 6 and 9 kb transcripts  [119] , and their polyadenylation sites (2 kb versus 6 kb)  [120]. The abundance of data in databases largely confirms the observed variations in splicing patterns and polyadenylation sites but also suggests the existence of several promoters, as detailed below.
The 5′ end of this sequence (approximately -7000 to 3000 nt), which has only been studied in mice, is also involved in promoter activity  [121]. In addition, a putative reverse sequence located immediately downstream of E0 might be involved in human MAPT regulation (Fig. 2 )  [64]. However, these authors could not exclude interference from another promoter because of identification of a hypothetical gene, LOC100128977, immediately upstream of and in the opposite orientation as the MAPT gene  [124]. According to the technique used, several initiation sites for Tau transcription have been reported in both rats and humans  [65, 77]. The human transcript sequences published in databases confirm the diversity of the transcription start sites. However, some discrepancies exist between the sites described in the literature and those in databases.
Does MAPT have only one promoter? Alternative initiation transcripts largely contribute to transcriptome and proteome diversity, and more than 40 % of genes have at least two promoters, as demonstrated in flies (reviewed in  [129, 130] ). Although the region around E0 contains the only promoter for MAPT that has been described in the literature, Andreadis  [57]  hypothesized the existence of additional Tau promoters to explain variations observed in neuronal specificity and NGF susceptibility of Tau expression according to the different Tau transcripts  [77, 119, 131]. Currently, new data are available in databases that reinforce this hypothesis; at least 6 other exons distal to E0 have been identified as the first exons of various transcripts. One of the potential additional promoters may be associated with the initiation of transcription at exon E1.
Indeed, considering the number of identified transcripts, E1 is the most frequent exon where transcription is initiated after E0 (transcripts initiated at E0: 9 and E1: 5) for the H1 haplotype, further suggesting the possible existence of an unidentified promoter. E1 is located 68000 nt distal to E0. Similar to E0  [57] , sequence analysis has revealed no TATA or CAAT consensus binding sites in E1; however, a GC box specific for SP family members is present near this exon  [132]. Indeed, one potential SP1 site and five sites for AP-2α binding have been identified 200 nt upstream of E1 using the ALGGEN server  [133]. The absence of E0 would result in a change in the 5′ UTR length but would not alter the coding sequence because E0 is a non-coding exon, while E1 is a partially coding exon (Fig.
1 ). On the reverse strand (H2 haplotype), transcripts listed in the Ensembl database begin primarily with E1  [125]  (Fig. 3 ). The other initiating exons near the E2, E3, E4A and E5 regions are located more than 10,000 nt and up to 25,000 nt distal to E1, suggesting that more than one alternative promoter may exist. Interestingly, the CpG 21 island is located immediately upstream of E4A at the beginning of the short transcript MAP-010/ENST00000576238, as described above in the CpG island section (Fig. 4b ).
Indeed, two possible 3′ splice sites exist for E4A (E4A, E4A Long ), and there are 3 splice sites for E6 (E6c, E6p, E6d)  [41, 117, 137]  (Fig. 4a ). However, although isoforms containing E4A Long , E6p, and/or E6d have been reported in the literature, they are not present in human databases (Ensembl, UCSC). These observations bring into question the frequencies at which these different 3′ splice sites are used. Considering the possible co-insertion of alternative exons, ENSEMBL/ UCSC sequences, E4A is always inserted when E6 or E6 and E8 are included with E2, E3 and E10. However, an E4A-containing isoform without E6 but containing E2, E3 and E10 has been cloned  [140]. Furthermore, in Ensembl database, the isoforms containing exon 6c also contain exons 2, 3, 4A and 10 with or without exon 8, although studies by Andreadis's group have demonstrated that all combinations of E6c, E6p, and E6d with the other alternative exons are possible  [141].
Suggestions from databases Recent data from databases suggest that the splicing pattern of MAPT may be more complicated than suggested by the primary characteristics described above, although particular splicing events are most likely rare. Although the majority of transcripts described in databases are coding transcripts, some are not (Fig. 4b ). Non-coding transcripts have been identified that correspond primarily to isoforms with the deletion of at least one constitutive exon. One such non-coding transcript (MAPT-011 ENST00000571311) (Fig. 4b ) may be processed by NMD. Notably, none of these variants have been described in the literature, although they are listed in Ensembl. Their existence and potential roles (perhaps as lncRNAs) remain to be investigated and confirmed. Splicing and H1/H2 haplotypes A comparison of the transcripts from the forward (H1) and reverse (H2) strands that have been published in databases such as Ensembl has revealed that the haplotype might affect some splicing events.