dataesr/scientific-paragraphs-categorization huggingface dataset:
FUnDing This research was supported by grants from ANR (ANR-15-CE21-0014); the Regional Council of Burgundy France (PARI Agral 1); the FEDER (European Funding for Regional Economic Development); and a PhD fellowship from the Nutrition, Chemical Food Safety and Consumer Behavior Division of INRA (French National Institute for Agronomical Research, France), and the Regional Council of Burgundy (France) to LM.
Costs data collection aspects We conducted a cross-sectional study using cost data collected retrospectively to estimate the cost-of-illness of cholera for households and health facilities. All the data were collected between February and March 2016 in parallel with the implementation of a mass oral vaccination campaign against cholera (February 16 to 22, 2016 and from March 8 to 15, 2016, for rounds 1 and 2, respectively). Expenses for an individual patient and for the health system were only counted once and did not include multiple disease episodes. Data from this study could be accessed through a request to the Agence de Medecine Preventive-AMP: website http://amp-vaccinology. org/fr/contact-amp.
Measuring household cost of cholera Only cholera cases reported from the last 7+ weeks (i. e. between February 4 th and March 26 th , 2016) preceding the data collection period were eligible for interviews. A total of 100 patients were purposefully recruited for the household cost-of-illness. Eligible patients were cases presenting with an infectious disease characterized by intense vomiting and profuse watery diarrhea, regardless of vaccination status, that received care over the previous five weeks. The sample included approximately 9% of the reported cases in the study. For patient recruitment, we systematically selected every fifth patient out of those who received treatment during the five weeks preceding the survey. This was achieved by reviewing line lists-which recorded patient details in a consistent manner-located at cholera treatment facilities in the two districts.
All selected patients were then visited in the community with the support of community-based health surveillance assistants, for face-to-face interviews in their homes to elicit costs incurred in seeking care. Interviews were conducted with the head of household, and/or the main patients' caregiver who was most familiar with the costs borne during the cholera episode. Five specifically trained interviewers collected data from all confirmed cholera patients by means of a pilot-tested structured questionnaire programmed on hand held tablets. Prior to fieldwork, interviewers were given comprehensive training on data collection procedures. We asked questions related to patients' demographic characteristics, disease duration, health expenditures including direct medical expenses on medicines, and consumables, direct nonmedical costs including transportation, foods and beverages and other miscellaneous expenses.
Data relating to treatment outcome, coping strategies used by households to compensate for direct and indirect costs were also collected. Moreover, we asked currently employed persons for the estimated number of days absent from work and related self-reported total income lost. For deceased patients, we estimated lost income by asking the patients' relatives to describe income lost during the patient's period of illness. Intangible costs (e. g. , costs of stigma from cholera), costs following death, and school days missed were not collected. Likewise, expenses relating to diagnostics and hospitalization were not considered in the household cost measurement as they were not supported by patients but covered by the Government. The household study questionnaire is given in the supporting document S1 Appendix.
Measuring health provider cost of treating cholera Facility-based surveys were undertaken in order to assess the costs to health providers for treating cholera cases. Four cholera treatment centres and one district hospital expected to manage cases were selected for data collection. Cost data collected included staff, medicines and consumables. Unit costs of medical services used to estimate the costs of treating cholera were directly measured from the study facility by standard methods. [25]  A micro-costing bottom-up approach was used to estimate the amount of medical items needed to treat a patient sick with cholera. Moreover, we reviewed the health facilities' registries and clinical files to assess quantities and prices of items used to treat cholera. This was complemented by a thorough interview of involved health personnel to investigate the time spent by health personnel in treating cholera patients and the number of cholera cases treated in each facility.
Data management and analysis Both household and provider databases were analyzed using Stata 13. 1 (StataCorp, College Station, Texas, USA). All monetary values were presented in 2016 US dollar using the annual conversion rate between US dollar and Malawian Kwacha (MWK) of US$1 = MWK696. 21. [26]  To allow comparison between countries, we converted Malawian Kwacha to 2016 international dollars (I$) using the appropriate purchasing power parity conversion factor given by the International Monetary Fund. [27]  Regarding the data from the households' interviews, a descriptive analysis was conducted to describe socioeconomic characteristics of patients and households and assess gender differences. The differences between proportions were tested using the chi squared test. The Mann-Whitney test was used to test for differences where distributions were skewed.
Seventh, cost data were collected retrospectively. This may have also contributed to distorting our cost estimates given possible recall biases, although minimized by the relatively shorter recall period. Eighth, we analyzed data from cholera cases independently of the vaccination status. Severity of cholera has been demonstrated to be lower among vaccinated people. [37]  Because of this, the cost of illness estimates reported in this study may have been underestimated. Finally, our study took a retrospective data collection approach while Poulos et al  [28]  and Sarker et al  [33]  adopted a prospective approach with two set of interviews and a mixed of retrospective and prospective approach, respectively. This may explain some of the differences observed in costs estimates. In contrast, Schaetti et al  [29]  used a study methodology that was similar to the current study approach.
The dataset generated contained private patient information that cannot be disclosed. In addition this research was conducted under local research ethics committee clearance. The dataset generated under this research cannot be widely disseminated at this stage given we did not receive permission from the MoH (doccentre@malawi. net) to do so. Nevertheless, data could be accessed by emailing AMP and by sending a request at http://ampvaccinology. org/fr/contact-amp or more directly by writing to Andree.
To date, >50 Gypsi GS patients are included in the Renaltube database and most of these patients are homozygous for the intron 9 splicing mutation. The index cases of Families I and II, were subjected to NGS to search for new SLC12A3 mutations, resulting in the identification of p. Val647Met. The p. Val647Met variant was predicted to be pathogenic with at least two bioinformatic programs (SIFT and Polyphen). This missense change locates at the intracellular carboxy-end of the protein (Fig. 2 ), where other GS mutations have been found and aminoacids at this region are conserved not only among species but also in other human channels such us bumetanide-sensitive cotransporter (SLC12A2 gene). 17 he p. Val647Met mutation had been previously reported by Vargas-Poussou et al. in one GS patient (PV.
Conflict of interest All authors declare that they have no conflict of interest. Consent of publication All authors approved the final version of the manuscript. Ethical approval This article does not contain any studies with human participants or animals performed by any of the authors. Funding This work was performed, in partnership with the SAS PIVERT, within the frame of the French Institute for the Energy Transition (Institut pour la Transition Energétique (ITE) P. I. V. E. R. T. (www. institut-pivert. com) selected as an Investment for the Future (BInvestissements d'Avenir^). This work was supported, as part of the Investments for the Future, by the French Government under the reference ANR-001. The Regional Council of Picardie and European Union co-funded equipment utilized within CPER 2007-2020.
Background The chicken leptin gene was recently identified, more than 20 years after the first identification of mammalian leptin  [1]. An extensive search for chicken leptin  [2] [3] [4] [5]  led to erroneous identification, characterization and mapping  ([4, 6-10]. While the erroneous mapping was retracted  [11] , the erroneous sequences of chicken, turkey and duck leptins were not withdrawn [GenBank: AF012727, AAC32381 and AAT38807], respectively. The high GC content of avian leptins [74 ± 2 (SE) %] is significantly higher than that in leptins from non-avian vertebrates [52 ± 3 (SE) %]  [1]  and contains repetitive and palindromic sequence elements. This observation pointed to the possibility that the avian leptins may be located on microchromosomes, which are known to contain these types of sequence elements and, in addition, are underrepresented in avian genomes assemblies  [12, 13].
For example, the average GC-content in chicken chromosome 1 is 40. 3% compared with an average of 56. 5% for chromosomes 25 to 33 [GenBank: GCA000002315. 3]. High-quality genome assemblies for chicken and other birds revealed a large proportion of missing genes compared to other vertebrates  [14, 15]. The presumed loss of the protein-coding genes was estimated to be as high as 30%  [14]. These missing genes often form synteny groups, which are conserved among vertebrates. Therefore, it has been suggested that these genes were lost from avian genomes during the evolutionary process when microchromosomes were formed in the avian lineage  [14, 15]. However, technical difficulties in identification of some avian genes, due to their sequence characteristics and high sequence divergence, have been suggested as an alternative explanation  [1, [16] [17] [18].
Characterization of RBM28 structure and expression In vertebrate genomes for which leptin and its syntenic group of genes are annotated, RBM28 is mapped adjacent to leptin. In most cases, it is in a tail-to-tail orientation (3′ to 3′; e. g. peregrine falcon, Falco peregrinus  [23, 24] ; fugu, Takifugu rubripes [GenBank Gene ID: 548,631]; green sea turtle, Chelonia mydas [GenBank Gene ID: 102,932,266]; and mouse, Mus musculus [GenBank Gene ID: 16,846]). Moreover, we have previously shown that leptin is very closely linked to RBM28 in peregrine falcon and fugu (1. 8 and 0. 4 kbp, respectively  [23] ). Since such close proximity and the conserved 3′ to 3′ orientation suggest a local regulation of transcription  [25] , we further characterized RBM28 and its expression pattern. We deduced the full-length cDNA of RBM28, using genomic and RNA-seq data available in GenBank (Fig.
2 ; Additional file 2: Fig. S1  and Table  S2 ). The assembled 2007 bp cDNA [ENA Project ID: PRJEB18741] was partially corroborated by a match to a single expressed sequence tag (EST, 838 bp, [GenBank: DR425791]). With 69% GC-content, this putative transcript was found to be capable of encoding a 668 aa polypeptide with 50-51% identity and 65% similarity to human and alligator RBM28 [GenBank: NP001159607; GenBank: XP006033669] (Fig. 2 ). Higher amino acid identity of close to 90% was observed within the 3 RNA Binding Motifs (RBMs), which aligned with RBMs 2-4 of the human ortholog, each of about 90 amino acids long. Chicken and alligator proteins had a structure layout consisting of only 3 RBMs suggesting that such layout is common to reptiles, turtles (e. g. green turtle [GenBank Gene ID: 102,932,266]) and to birds (e.
g. peregrine falcon [GenBank Gene ID: 102,049,081], while in mammals it retained the 4 RBM composition that is present in fish (e. g. fugu, [GenBank Gene ID: 548,631]). The acidic region between RNA recognition motifs 2 and 3, reported for the human RBM28  [26] , was found to be only partially conserved in the deduced proteins of chicken and alligator, but it was followed by an additional acidic region in chicken RBM28 (annotated 281-309, Fig. 2 ). Among the    S1 ). b Synteny conservation between the distal part of chicken chromosome 1p (GGA01) and human chromosomes 22 (HSA22, reddish colors) and 7 (HSA07, blueish colors) 18 exon-intron junctions, 13 were found to be conserved between the chicken and the human genes (Fig. 2  and Additional file 2: Table  S2 ). We used a comprehensive RNA-seq experiment of a female and a male red junglefowl available in GenBank (Chickspress, [GenBank: PRJEB4677]) to characterize the RBM28 expression pattern.
The broad expression pattern obtained by searching the data for tissues included in this experiment (Fig. 3a ) seemed compatible with the housekeeping role of RBM28 as a nuclear component of the spliceosomal ribonucleoprotein complex  [26]. Nevertheless, the variation in expression level between tissues suggests tissue-specific functional roles. To explore the possibility that the conserved proximity of leptin and RBM28 relates to their transcriptional control, the expression profile of chicken leptin was explored using the same RNA-seq dataset. Comparison of the two patterns revealed that the tissues with the highest expression of RBM28 (adipose, lung, heart and spleen) had no significant leptin mRNA, whereas, tissues expressing leptin (cerebellum, cerebrum and hypothalamus) had only a basal level of RBM28 expression (Fig.
02; Fig. 4b ). Also in these two strains of chickens, leptin was not significantly expressed in visceral fat. For comparison, we searched RNA-seq dataset from obese and lean human [GenBank: SRX470443-45] and, as expected, leptin expression was higher in adipose tissue of obese individuals (P = 0. 04;  [29] ). However, the expression of RBM28 was not significantly different between obese and lean humans (Fig. 4c ).
RH mapping PCR amplifications were carried out for each marker (Additional file 1: Table  S1 ) in 15 μl reactions containing 25 ng DNA from the RH panel  [21] , 0. 4 μM of each primer, 0. 25 units Taq polymerase (GoTaq, Promega), 1. 5 MgCl2, 0. 2 mM dNTP, using the Applied Biosystems 2720 thermal cycler. The first 5 min denaturation step was followed by 35 cycles, of denaturation at 94 °C for 30 s, annealing at Tm for 30 s and elongation at 72 °C for 30 s. Each marker was genotyped twice and a third genotyping was performed in case of discrepancy between the first two determinations. The RH map was built as previously described  [39]  using the Carthagene software  [40]  and drawn with MapChart 2. 0  [41].
Bioinformatic analysis Sequence homology searches were carried out at NCBI [non-redundant nucleotide collection (NR), SRA, and WGS] using the BLAST family of programs. Relevant sequence entries were downloaded with their quality information (FASTQ format) and reassembled using either MIRA4  [42]  or GAP5 software  [43]. Sequences were aligned using CLUSTALW or MAFFT (http://www. genome. jp/tools/clustalw) with the default parameters and the GONNET matrix or E-INS-I strategy for amino-acids and nucleotides, respectively; and colored using the BOXSHADE program (http://www. ch. embnet. org/software/BOX_form. html).
Additionally, anti-fibrinolytics and occasionally androgens can reportedly be useful for long-term prevention of attacks, and curing a causal underlying disease may be an option in some patients  [9]. For C1-INH-AAE associated with autoantibodies, when prophylactic treatments are insufficient, rituximab (MabThera V R ; Roche, Mississauga, Ontario, Canada) can be an effective option  [6]. Given the limited clinical data on treatment options for these rare disorders, information gleaned from drug registries can help to gather valuable insight into the utility of medications in these patients. The Icatibant Outcome Survey (IOS) is a registry that was designed to monitor the safety and effectiveness of icatibant in the real-world setting. Although this agent is approved currently (in Europe and the United States) to treat angioedema attacks in patients with C1-INH-HAE, in countries where the appropriate regulatory approvals have been granted, any patient with a prescription for icatibant is eligible to participate in the IOS, including those who are receiving icatibant offlabel for C1-INH-AAE.
Study design IOS is an ongoing, international, prospective observational study (NCT01034969) monitoring the safety and effectiveness of icatibant during real-world use. This registry was initiated in 2009 by Shire (Zug, Switzerland); by April 2015, 50 sites in 11 countries participated, including Austria, Brazil, Denmark, France, Germany, Greece, Israel, Italy, Spain, Sweden and the United Kingdom. The study design is described in detail elsewhere  [13]. Briefly, physicians completed electronic forms when their patients attended routine clinic visits, approximately every 6 months. A description of each attack that occurred between clinic visits was recorded, including the anatomical site(s), severity, time of administration of icatibant injection(s) and rescue medications, the point at which symptoms were resolved and whether the drug was self-administered or delivered by a health professional.
However, it is also possible that icatibant is more effective in this group of patients with increased consumption, rather than in patients with a genetic C1-INH deficiency. Unlike the case with treated attacks, the duration of untreated attacks involving the skin and abdomen that occurred within 12 months before enrolment in the IOS was not shorter in patients with C1-INH-AAE than in those with C1-INH-HAE types I/II, further emphasizing the possibility that icatibant is a more effective treatment in patients with C1-INH-AAE. Key limitations of this analysis include the fact that some data were missing due to incomplete descriptions of attacks, and there was a lack of controlled conditions in this observational retrospective study; statistical testing was considered exploratory. Also, patients with C1-INH-AAE were evaluated against patients within a different age group and with slightly different characteristics of angioedema attacks.
Additionally, there were only 16 patients with C1-INH-AAE compared with 415 patients with C1-INH-HAE types I/II. Finally, the retrospective documentation of attacks may have reduced the accuracy of the results. Ideally, patients with C1-INH-AAE would be evaluated in a controlled study. However, given the rarity of this disease, conducting such a study is challenging and speaks to the general difficulties in identifying large enough patient samples to conduct clinical trials for rare diseases. From this perspective, the collection of real-world data from drug registries provides valuable insight that helps to support clinical trial data while assessing real-life product use and treatment patterns, thus increasing our understanding of the natural history and epidemiology of rare diseases. Hence, findings such as those reported here may help improve understanding of the nature of angioedema attacks, patient demography and the utility of treatment for patients with C1-INH-HAE and C1-INH-AAE.
Acknowledgements This research was funded by  Shire Development, LLC. Under the direction of the authors,  Clare Guni BMBS ,  Sally Hassan PhD  and  Sophia Shumyatsky PharmD , employees of Excel Scientific Solutions, provided writing assistance for this publication. Editorial assistance in formatting, proofreading, copy-editing and fact checking was also provided by  Excel Scientific Solutions. Shire Development, LLC  provided funding to  Excel Scientific Solutions  for support in writing and editing this manuscript. The interpretation of the data, and the decision to submit the manuscript for Disclosure H. J. L. has received research grant support and/or speaker/ consultancy fees from  BioCryst ,  CSL Behring ,  Dyax ,  Shire  and  Sobi. A. Z. has received speaker fees from  CSL Behring, Shire  and  Sobi ; consultancy fees from  CSL Behring and Shire ; and has acted on medical/advisory boards for  CSL Behring and Shire.
FUNDING This work was supported by the  Centre National de la Recherche Scientifique (CNRS) , the  Institut National de la Santé et de la Recherche Médicale (INSERM) , the  Université de Bourgogne-Franche Comté  (grant BQR), the  Agence Nationale de la Recherche  ( ANR ;  ANR-13-JSV1-0003-01 ), and by a  French Government  grant managed by the  ANR (Program "Investissements d'Avenir "  ANR-11-LABX-0021-01-LipSTIC LabEx ).
In the scientific opinion on FGE. 57, the Panel concluded that no NOAEL could be derived for (1R,2S,5R)-isopulegol [FL-no: 02. 067], (2R,5S)-isopulegone [FL-no: 07. 067] and (1R,2S,5R)-isopulegyl acetate ]. Accordingly, additional toxicity data were requested for the three substances. In the present revision (FGE. 57Rev1), a 14-day range finding study (Mendes, 2012) and a 90-day dietary study (Koetzner, 2013) have been provided for (1R,2S,5R)-isopulegol ]. These studies, covering also the evaluation of the structurally related (2R,5S)-isopulegone [FL-no: 07. 067] and (1R,2S,5R)-isopulegyl acetate [FL-no: 09. 219], are evaluated by the Panel. Information on the stereoisomeric composition of [FL-no: 02. 067, 07. 067 and 09. 219] and their use levels in food has also become available and included in the present output  (EFFA, 2014 (EFFA, , 2017)).
EFSA considerations For all substances, industry has submitted production figures for the EU. For (1R,2S,5R)-isopulegol [FL-no: 02. 067], (2R,5S)-isopulegone [FL-no: 07. 067] and (1R,2S,5R)isopulegyl acetate [FL-no: 09. 219], the flavour industry submitted use levels for normal and maximum use  (EFFA, 2017). Based on these normal use levels, the mTAMDI values were calculated. Isopulegyl acetate [FL-no: 09. 219] has mTAMDI intake estimate below the threshold of concern for its structural class. For (1R,2S,5R)-isopulegol [FL-no: 02. 067] and (2R,5S)-isopulegone [FL-no: 07. 067], the mTAMDI values are above the toxicological thresholds of concern for their structural classes of 1,800 and 540 lg/person per day, respectively. Therefore, for these two substances, more reliable exposure data are required in order to finalise their evaluation.
5. Toxicity data on isopulegol 5. 1. 14-Day and 90-day study on (1R,2S,5R)-isopulegol [FL-no: 02. 067] 5. 1. 1. 14-Day oral range-finding toxicity study A 14-day range-finding dietary study was performed with (1R,2S,5R)-isopulegol [FL-no: 02. 067] (Mendes, 2012). The study was not in full compliance with GLP. Moreover, although it was stated to be performed according to OECD Test Guideline 407 (repeated dose 28-day oral toxicity study in rodents), a full study according to OECD Test Guideline 407 would encompass a 28-day exposure period and larger groups of animals. In addition, the number of parameters studied was far more limited than required for a full OECD Test Guideline 407 study  (OECD, 2008). CRL Sprague-Dawley CD â IGS rats (three per sex per group) were exposed to (1R,2S,5R)isopulegol (microencapsulated in acacia gum) via the feed at dietary levels of 2,400 (Group 2), 9,000 (Group 3) and 36,000 (Group 4) mg microencapsulated isopulegol-containing acacia gum/kg feed.