dataesr/scientific-paragraphs-categorization huggingface dataset:
1988 To provide reliable data on the epidemiology of IBD to healthcare authorities, provide data to search for a cause of disease, and describe in a population-based setting the natural history and real-life management of IBD All IBD patients in region (approximately 20000 patients) Patient demographics and disease data SWIBREG [35]   Sweden 2005 To serve as a decision support tool in everyday life, assessing disease activity and quality of life > 40000 (adult and pediatric) Patient demographics and disease data, drug history, treatment and disease outcomes, surgical interventions, patient-reported outcomes. Capacity to enter information about comorbidities SIBDC [12]   Switzerland 2005 To build understanding of the consequences of IBD on the physical, mental, and social conditions of IBD patients Voluntary national database of > 2500 patients Patient demographics, disease and treatment information.
Patient blood samples are kept in a biobank providing a databank of genetic and disease information UK IBD Registry [13]   United  [36]   Austria and Germany 2004 Developed and operated by the working group of chronic inflammatory bowel diseases of the Society for Pediatric Gastroenterology and Nutrition; aims to improve the care of children and adolescents with IBD. Approximately 1000 Patient demographics, disease and treatment data SPIRIT-IBD [37]   Spain 1996 To understand the incidence and prevalence of IBD in pediatric patients Approximately 2000 Patient demographics, disease and treatment data EUROKIDS [38,39]   Europe and Israel.
Despite the coverage of these registries, the initial research questions used, the configuration of datacollection systems, and available resources (both financial and personnel) all impose limits on the data they can gather. Information about medications to treat conditions concomitant to IBD, such as ID and IDA, may not be captured. Similarly, the collection and inclusion of patient-reported outcome (PRO) data in existing IBD registries is not a trivial undertaking. Given the importance of ID-related symptoms, the collection and analysis of PRO questionnaires is important and should be considered.
HOW SHOULD IDA-RELATED DATA BE COLLECTED IN IBD REGISTRIES? Although national healthcare databases collect and store data from blood tests on anemias, ID, and the drugs used in their treatment, they do not seem to be an appropriate way to collect data on IDA in IBD. In general, such databases are optimized to collect highlevel administrative data, and do not describe IBD patients adequately to offer the level of medical detail needed to research the natural history of disease. This is also the case for databases owned by agencies involved in reimbursement of medical treatment. From this, a clear need for prospective and specific collection of iron parameter data can be established, which may be achieved through the adaptation of existing IBD registries. Even though IDA and ID are common in IBD, and exert a substantial burden on patients and healthcare systems  [8] [9] [10]  , none of the established European IBD registries systematically collects information on iron parameters and related outcomes.
Addressing this shortfall in data collection requires examination of the primary objectives of the registries in question, and consideration of parameters that could answer further research questions around this objective. The parameters collected would be determined by the type of registry (condition-, product-, or service-based) and should serve its primary research objective; suggestions and service delivery. Some information is registry specific, such as biobanking of blood samples for genotyping, as within the Swiss cohort  [12]. It is notable that, despite the prevalence of ID/IDA among IBD patients, none of the registries identified explicitly were collecting information on iron parameters and related outcomes in a systematic manner at the time of this review. The approach to data collection and verification varies among registries.
For example, in EPIMAD (Registre des Maladies Inflammatoires Chroniques de l'Intestin du Nord Ouest de la France), data are collected by interviewer practitioners when possible    2. A condition-based registry designed to monitor epidemiology of IBD could also collect data to provide snapshots of the prevalence and severity of IDA. Longitudinal analyses of IDA duration and disease course, with the potential to identify commonly associated factors-including ID-related burden occurring during pregnancy-could also be included. To chronicle the natural history of IDA, it is necessary to collect longitudinal information on clinical, biochemical and endoscopic disease activity; data from imaging techniques such as magnetic resonance imaging should ideally be included. In line with the current European Crohn's and Colitis Organisation (ECCO) consensus on the diagnosis and management of ID with and without anemias in IBD [15] , a basic dataset may comprise hemoglobin levels, transferrin saturation and serum ferritin levels, and perhaps mean corpuscular volume and mean corpuscular hemoglobin.
There are several tools available to measure QoL in patients with IBD or, more recently, disability [17,18] , although these do not necessarily distinguish between the burden of ID/IDA and IBD. A product-based registry (focused on IBD treatment) could be used to monitor use of iron supplements. Information on prescribed iron replacement therapy, including doses, may be recorded as either oral or intravenous, to illustrate any impact of a different choice of iron administration route. A service-based registry would typically have a different dataset, including information on the use of healthcare (including hospitalizations and surgery),. If an economic perspective is deemed valuable, observations on impaired work productivity and activity can be collected, as well as information on absences from work or full-time education, healthcare attendance, need for surgery, and medication adherence and persistence.
Correlation between disease registries in IBD, oncology, heart failure, and mental health could offer completely new perspectives on improving the multidisciplinary care of patients with ID. Further connections could be made with drug prescription databases with the intention of correlating disease outcomes with specific treatment information. Linkage of an IBD registry with national service-based registries could show the frequency of outpatient visits, inpatient care, surgery, and co-existing disease, based on the international classification of disease codes. Linkage with mortality databases would provide an additional view of disease outcomes. A potential barrier to sharing of data is the governance issues around information. Any such sharing should comply with the registry's ethical requirements and national laws covering data protection.
PARAMETERS? The current IBD registries are positioned well to collect iron parameter data and link these with IBD-specific data. Although it is beyond the scope of this article to provide detailed guidance on adapting a registry to collect a new set of variables, there are several factors that should be considered, in regard to the prospective collection of iron parameters in an IBD registry. Initially, it is important to consider the change in scope of a registry, in terms of its expected redefined purpose, objectives, and overall outputs. While it may be tempting to maximize the opportunities for data collection, this must be balanced against the importance of collecting high-quality, reliable data with no significant increased burden associated with their entry to the database. Limiting the scope of a registry ensures that specific objectives and well-defined research questions can be established in order to specify what outputs should be sought.
Defining and confirming the scope of any changes with all stakeholders will optimize the work needed as the changes to the registry are implemented. When the objectives have been clearly established, the data to be collected can then be determined. The data collection method should suit the data type. The practicalities of incorporating collection of iron parameters into an existing IBD registry could present a challenge, as it would depend on the healthcare system in which the registry operates. Ideally, the addition of new parameters to a registry should not generate substantially more work for sites contributing to the registry. With the introduction of electronic medical records and network integration it is theoretically possible for iron parameter data from medical laboratories to be automatically added to a medical record and uploaded to a registry database.
The rise in health technologies that are accessible from personal mobile devices is likely to have an important role in collection of PROs. Electronic PRO data collection has many advantages relating to easy, accurate, and complete collection of data that is potentially of great value to investigators and healthcare systems  [25]. In the context of a registry, as opposed to a clinical trial, it may make sense for a patient to be able to complete PRO information using their own mobile device, rather than attending an appointment. Although this adds a level of convenience for both patient and healthcare team, a number of barriers still remain including data security, patient compliance with data collection, and what to do if a patient does not possess a suitable device  [25]. Nevertheless, ePROs show promise; indeed, pilot studies of an electronic data submission method implemented by the SWIBREG registry have proved successful and its launch is imminent in some regions in Sweden.
A UK study to collect ePROs in an elective orthopedic setting showed great promise, gathering reliable data but also highlighting that the ePRO system may not be adequate for some patients  [26]. The incorporation of iron parameter data into European IBD registries offers great opportunities to improve the care of IBD patients. Firstly, highlighting the prevalence of IDA in the IBD population would show the unmet need in this patient group in countries across Europe. It is notable that the ECCO guidelines for diagnosis and management of ID and IDA in IBD recommend that all patients with IBD should be assessed for the presence of anemia  [15]. Robust data are necessary to heighten awareness of the importance of IDA in IBD and to lobby healthcare systems to improve access to the full range of iron supplementation therapies.
Beyond the local and national level, the collection and comparison of iron parameters by multiple registries would allow the relationship between IBD and IDA to be examined from different perspectives, stemming from each registry's specific remit, leading to the generation of new research questions and ultimately improving patient care. A further possibility would be the pooling of data between national registries to identify and study any differences in patterns of disease, and to compare practices in healthcare service delivery. A very large dataset should also able to highlight any rare effects that might not be evident from a single national registry. This initiative would, of course, require agreement on the collection of a basic dataset and standardization of methodologies, as well as addressing how data should be anonymized and aggregated to comply with the legal aspects of sharing data across national borders.
Due to similarities between symptoms of IBD and ID/IDA, the identification of ID/IDA-specific symptoms in the IBD population is necessary. There is, therefore, a clear need to collect robust, structured data around ID/IDA in IBD, its treatment, and on related service delivery. Despite potential limitations (possible selection bias and potential variability in data quality), it has been suggested that 'real-world' data have a greater applicability to the routine clinical setting than the findings of controlled trials  [5]. Current digital technologies and networking capabilities raise the prospect of an acquisition and analysis of real-world data that is (and should be) easier than ever before. With appropriate planning, information governance structures, adaptation, and negotiation, registries are ideally placed to collect this information in a routine clinical practice setting.
Two independent T-DNA lines were identified for each PPR gene. Each mutant pair exhibited very similar phenotypes, supporting that the observed growth alterations were due to the inactivation of the corresponding PPR genes. The lines misf26-1 (SALK_008252), misf26-2 (SAIL_363_F11), misf68-2 (SALK_010785), misf74-1 (SALK_054210), and misf74-2 (GABI_191C05) contained T-DNA insertions within the PPR repeat coding regions of each corresponding gene, while the T-DNA of the misf68-1 (SALK_062109) mutant is located upstream of the first PPR repeat coding sequence of MISF68. The genes MISF26, MISF68, and MISF74 encode proteins that are predicted to comprise 11, 14, and 10 P-type PPR repeats, respectively, according to TPRpred (https://toolkit. tuebingen. mpg. de/#/tools/tprpred) and the PlantPPR database (http:// ppr.
The AT4G01400, AT3G16010, and AT1G66345 PPR proteins are targeted to mitochondria in vivo The three identified PPR proteins were predicted to reside in mitochondria according to the Arabidopsis subcellular database SUBA (http://suba3. plantenergy. uwa. edu. au/). To verify their subcellular distribution, we generated GFP translational fusion constructs comprising the region encoding the putative mitochondrial transit peptide of each PPR protein and then transformed them into Arabidopsis Col-0 plants. Confocal microscopy was used to detect the GFP fluorescence in the roots of the generated transgenic plants. In all cases, we observed GFP signals that co-localized with MitoTracker red signals in mitochondria (Fig. 2 ), which confirmed the mitochondrial localization of the three PPR proteins in vivo.
Patients In this retrospective study, we enrolled all patients evaluated at a French national reference centre for juvenile arthritis in Necker-Enfants Malades hospital and the paediatric rheumatology outpatient clinic of Saint-Vincent-de-Paul Hospital between January 2008 and December 2015. Patients were recruited through the "Centre de Référence des Maladies Rares (CEMARA)" database project  [11]. The recording of patient, parent information, data collection and analysis were conducted in accordance with French national guidelines. CEMARA has been authorized by the French National Committee on Informatics and Liberty. According to French legislation, patients and parents were informed, but informed consent was not required for a retrospective analysis. The inclusion criteria were having ERA or JSpA, with disease onset at an age of less than 16 years, diagnosed by the attending physician, and confirmed at the latest follow-up visit.
Data collection For each patient, we collected information concerning gender, age at disease onset, age at first visit, personal and familial history of inflammatory and auto-immune disease and psoriasis, presence of the HLA-B27 allele, description of the clinical course, date of first axial involvement, and biological and radiological tests from the medical chart. Data collection was performed two times by one investigator, first from the computerized medical chart and then from the paper chart. We also analysed the response to various treatments and adverse events. We noted any history of uveitis, psoriasis, or IBD to highlight extra-articular manifestation. Imaging data were recorded and analysed as described below.
Baseline characteristics Between January 2008 and December 2015, 373 patients were seen in our centre for a suspicion of ERA or JSpA. We excluded 34 patients with other diagnoses and 225 followed for less than one year, because they were mainly seen for a second opinion from our National reference centre and then included in the CEMARA database but followed afterwards in their regional centre. We included 114 patients (Fig. 1 ). The median follow up was 2. 6 years (1. 0 to 7. 2 years). The baseline characteristics are presented in Table  1. At the beginning of follow-up, only 53 patients (46%) of our population were classified in the ERA group, according to the Edmonton classification criteria, with a significant difference between boys and girls (57% versus 29%, respectively, p < 0. 01) and two patients (1.
Metagenomic Reads Associated with SK152 We identified 266 Salmonella enterica sequence reads in one tooth from skeleton SK152 and many more Salmonella sequences from additional libraries from SK152 teeth and bone, but not from dental calculus (Table  1 ). We attempted to reconstruct this Salmonella genome (henceforth designated ''Ragna'') from the SK152 sequence libraries. Concoct  [12]  was able to reconstitute 11 near-complete microbial genomes from those data (Figure  1D ). Nine of these genomes likely reflect recent soil contamination because their 5 0 -single-stranded deamination rates were low  [15] , with DNA damage < 0. 22, versus values of 0. 47 for human DNA and 0. 9 for Ragna. The two other assembled genomes exhibited high levels of DNA damage and are thus likely to have been endogenous to this corpse since burial.
Our final dataset comprised 219 modern Para-C-lineage genomes, isolated between 1914 and 2015 from multiple continents (Table  S1 ). A maximum-likelihood tree of the core SNPs within the 219 genomes showed that they fell into well-defined sub-lineages within each serovar (Paratyphi C: PC-1, PC-2; Choleraesuis: CS Kunzendorf, CS sensu stricto, CS-3; Typhisuis: TS-1, TS-2) (Figure  2B ). We also calculated a pan-genome, which was used to map the SK152 metagenomic reads after initial processing and de-duplication. Mapping identified 1,030,108 unique Salmonella reads in teeth (0. 05%-0. 18% of all reads) or the femur (0. 01%), but not in dental calculus (Table  1 ). All of these reads were specific to Paratyphi C and covered 98. 4% of a reference Paratyphi C genome (RKS4594) with a mean read depth of 7.
Alternatively, Typhisuis may have specialized from a generalist life style to a host specificity for swine. Our identification of the Ragna genome from a young woman who died in 1,200 CE provides insights on the genomic contents of the stem lineage of serovar Paratyphi C. The Ragna genome also demonstrates that salmonellosis was a deadly invasive disease of humans for centuries before its first recognition by physicians. Our analyses show that reconstructing the longterm evolutionary history of bacterial pathogens benefits dramatically from comparisons of metagenomic data from ancient samples with population genetic data from presentday bacteria. The close relationship between clades of the Para C lineage that differ in host specificity triggered intriguing speculations about historical host jumps during the Neolithic period between humans and their domesticated animals.
Isotopic fractionation was corrected using the d 13 C values measured on the AMS. The quoted d 13 C values were measured independently on a stable isotope mass spectrometer (to ± 0:3 per mil relative to VPDB). For details of the chemical pre-treatment, target preparation and AMS measurement see  [84, 85]. Figure  S1B  shows calendar age ranges calculated by the OxCal computer program (v4. 2) of C. Bronk Ramsey  [48] , using the 'IntCal13' dataset  [86]. These calculations support dates of 994-1052 CE with 53% likelihood and 1081-1152 CE with 42% likelihood. We summarized these results as 1,073 ± 79 years, which is the mean ± range of the lowest and highest extremes.
Genomic assemblies from metagenomic sequences of samples from SK152 Genomic assemblies from metagenomic reads Taxonomic profiling of metagenomic reads with currently available traditional methods can yield false indications of the presence of bacterial pathogens because pathogens are over-represented in public databases relative to environmental organisms, and completed genomes of many environmental bacteria are not yet available. As a result, ecological metagenomic analyses have used de novo assemblies of raw reads  [89]  but this has not yet been applied in aDNA studies. We therefore investigated whether de novo assemblies could reveal the presence of bacterial pathogens within the nine metagenomic libraries from SK152, and used subsequent analysis of deamination rates to determine whether those assemblies were ancient or modern.
C72 was initially assigned to Mogibacterium timidum, but only few related reference genomes existed in NCBI. We therefore compared C72 against the rMLST database [91] which contains > 200K genomes representing over 6,000 bacterial species. To this end, the translated amino acids of representative alleles in the rMLST database were mapped onto C72 using TBLASTN. This identified the positions of 46 of the 53 ribosomal genes. Those 46 ribosomal genes were then compared against all genomes in the rMLST database using TBLASTN. Analyses of both concatenated sequences and gene-by-gene analyses showed that C72 was more similar to Eubacterium sulci (74% identity) than Mogibacterium timidum (70%). We therefore re-assigned C72 to Eubacterium.
Details of these schemes are available on the Help pages at EnteroBase. For Salmonella, these MLST schemes currently include a 7 housekeeping gene legacy scheme  [3]  and rMLST based on 51 ribosomal proteins as defined by Jolley et al. [91] , and whose reference allelic sequences are maintained at the primary rMLST database at Oxford University  [91]. EnteroBase also calculates alleles for wgMLST based on a pan-genome of 21,065 genes. In brief, the wgMLST scheme encompasses unique sets of homologs with R 70% pairwise amino acid similarity over 50% of their length, and which were defined on the basis of 537 diverse, high quality Salmonella genomes. These homolog sets are usually either absent from individual Salmonella genomes, or are present only in a single copy. cgMLST (core genome MLST) V2 consists of that subset of 3,002 loci from the wgMLST scheme which met the following conditions for the 3,144 rMLST STs in S.
Pooled libraries (40 samples per run) were denatured following the Illumina protocol, and 600 ml (approx. 20 pM) was loaded onto a MiSeq V2 À500 cycle cartridge (Illumina), and sequenced on a MiSeq to produce FASTQ files of short reads. The short reads were uploaded to EnteroBase and to the Short Read Archives. Their metadata and genome properties are summarized together with other genomes of the Para C lineage in Table  S5  and can be examined interactively in the EnteroBase public workspace Para C lineage (see Key Resources Table ). Salmonella short reads from metagenomic aDNA Initial analyses Metagenomic reads from 33 human skeletons from Trondheim, Norway were screened using KRAKEN  [42]  with its default genomic database (Workflow, see Key Resources Table ). KRAKEN scored 304 metagenomic reads from skeleton SK152 as being Salmonella, and did not score any reads from the 32 other skeletons as Salmonella or other potentially invasive bacterial pathogens.
However, the taxon assignments provided by KRAKEN can be problematical when reads are present at low concentrations  [99]. In our hands, the KRAKEN analyses of SK152 also failed to identify seven of the eleven taxa that yielded assembled MAGs with CONCOCT (Concoct 6; Concoct 7, see Key Resources Table ). We therefore tested the reads from SK152 that had been identified as Salmonella by ad hoc BLASTN alignments to a custom database based on 91,000 bacterial, archaeal, and viral genomes from the non-redundant nucleotide database in GenBank, and confirmed that 266 (87%) scored as S. enterica. MGPlacer  [58]  was then used to iteratively map those Salmonella-specific metagenomic reads onto a core SNP phylogeny based on one genome from each of the 20 Salmonella serovars represented in RefSeq (May, 2016).