dataesr/scientific-paragraphs-categorization huggingface dataset:
Contributions: Conceptualization, M. Q. , H. C. -v. d. G. , A. N. , A. D. B. d. l. P. and N. R. ; validation, M. K. A. and N. R. ; formal analysis, L. T. ; investigation, M. Q. , H. C. -v. d. G. , A. N. , A. D. B. d. l. P. and N. R. ; data curation, M. Q. , H. C. -v. d. G. , A. N. , A. D. B. d. l. P. and N. R. ; writing-original draft preparation, L. T. and N. R. ; writing-review and editing, M. Q. , H. C. -v. d. G. , A. N. , A. D. B. d. l. P. and M. K. A. ; visualization, L. T. , M. K. A. and N. R. ; supervision, N. R. ; funding acquisition, M. Q. , H. C. -v. d. G. , A. N. , A. D. B. d. l. P. and N. R. All authors have read and agreed to the published version of the manuscript. Funding: This work was supported by the European Union Seventh Framework Programme (grant 305373 [FP7/2007-2013]) and the Deutsche Forschungsgemeinschaft (Heisenberg Professorship 325768017 to NR and Projektnummer: 314061271-TRR205 to N.
Acknowledgments: We thank all participants of the DSD-life study. The dsd-LIFE Group:  Birgit Köhler ,  Berlin, Germany; Peggy Cohen-Kettenis and Annelou de Vries, Amsterdam, the Netherlands; Wiebke Arlt, Birmingham, United Kingdom; Claudia Wiesemann, Göttingen, Germany; Jolanta Slowikowska-Hilczer, Łódź, Poland; Aude Brac de la Perrière, Lyon, France ;  Charles Sultan and Francoise Paris, Montpellier, France ;  Claire Bouvattier, Paris, France; Ute Thyen, Lübeck, Germany; Nicole Reisch, Munich, Germany; Annette Richter-Unruh, Münster, Germany; Hedi Claahsen-van der Grinten, Nijmegen, the Netherlands; Anna Nordenström, Stockholm, Sweden ;  Catherine Pienkowski , Toulouse, France; and  Maria Szarras-Czapnik , Warsaw, Poland.
Author Contributions: Conceptualization, M. Q. , H. C. -v. d. G. , A. N. , A. D. B. d. l. P. and N. R. ; validation, M. K. A. and N. R. ; formal analysis, L. T. ; investigation, M. Q. , H. C. -v. d. G. , A. N. , A. D. B. d. l. P. and N. R. ; data curation, M. Q. , H. C. -v. d. G. , A. N. , A. D. B. d. l. P. and N. R. ; writing-original draft preparation, L. T. and N. R. ; writing-review and editing, M. Q. , H. C. -v. d. G. , A. N. , A. D. B. d. l. P. and M. K. A. ; visualization, L. T. , M. K. A. and N. R. ; supervision, N. R. ; funding acquisition, M. Q. , H. C. -v. d. G. , A. N. , A. D. B. d. l. P. and N. R. All authors have read and agreed to the published version of the manuscript. Funding: This work was supported by the European Union Seventh Framework Programme (grant 305373 [FP7/2007-2013]) and the Deutsche Forschungsgemeinschaft (Heisenberg Professorship 325768017 to NR and Projektnummer: 314061271-TRR205 to N.
Methods A two-step search process was conducted to identify (i) systematic reviews, with/or without meta-analyses, or scoping reviews and (ii) experimental studies evaluating the effects of any type of religious fasting on health outcomes in apparently healthy individuals (not physically active individuals and athletes) and patients. In the first step, to identify systematic reviews, with/or without meta-analyses, or scoping reviews, a systematic literature search was conducted in five databases (PubMed, Web of Science, Cochrane, EBSCOhost, Scielo) on August 10th 2022. An additional search on Google Scholar was conducted on August 15th 2022. The following terms were used (see Table  S1 ): "Religious fasting, " "faith-based fasting, " "human, " "health, " "scoping review, " "systematic review, " and "meta-analysis.
" Appropriate Boolean operators were used to join the various keywords. Field tags, wild-card options (i. e. , truncated words), and medical subject headings (MeSH) terms were also incorporated where appropriate. In the search strategy, no language or date limits were applied. The full search strategy for all databases is presented in Table  S1. References of included papers were manually verified for a comprehensive search for relevant reviews. Personal files were also searched. In the second step, experimental studies were searched on August 10th 2022 in Google Scholar using the following terms: "Religious fasting, " "faith-based fasting, " "human" and "health. " To identify experimental studies published after the date of the last search of the most recent comprehensive review, date limits were applied.
Additionally, no significant adverse effects have been reported  (170). Lee and Krawinkel (168) compared body composition and nutrient intake data of 54 Buddhist vegetarian nuns and 31 omnivore Catholic nuns from South Korea. The authors found (i) nutrient intake of Korean Buddhist vegetarians was comparable to that of omnivores, and (ii) the intake of some nutrients in Buddhist vegetarians was more favorable than in omnivores  (168). Additionally, Buddhist vegetarians had higher fat-free mass, body fat, and BMI than omnivores, and body fat was inversely correlated with the duration of vegetarianism for vegetarians  (168). Future studies evaluating the effect of Buddhist fasting in high-risk populations are warranted.
It should be noted that undertaking physical activity in a fasting state improves body composition (i. e. , body fat) and some metabolic indices (e. g. , HDL-cholesterol)  (192, 193). Finally, the frequency of emergency department admissions appears not to change  (194) (195) (196) (197) (198)  or even decrease  (199)  during Ramadan, suggesting no adverse effects regarding the safety of fasting during the month of Ramadan. Nevertheless, data related to the effect of other types of religious fasting on the frequency of emergency department admissions are lacking. Given the healthy diet and the possible intake of water characterizing other religious fasting regimens, it is hypothesized a decrease in the frequency of emergency department admissions will be observed. Taken together, religious fasting regimens appear safe and beneficial for public health.
Invasive meningococcal disease (IMD) carries a high burden in terms of mortality, long-term complications, and cost, which can be significantly reduced by vaccination. The objectives of this case-control study were to document the care pathways of patients with IMD before, during, and after hospitalization and to assess inhospital complications and long-term sequelae. Cases consisted of all people hospitalized for IMD in France between 2012 and 2017. Controls were matched by age, gender, and district of residence. Data were extracted from the French national public health insurance database on demographics, hospitalizations, mortality and potential sequelae of IMD. Overall, 3,532 cases and 10,590 controls were assessed and followed up for 2. 8 years (median). During hospitalization, 1,577 cases (44.
14 In particular, it would be useful to document how many patients are hospitalized in a timely manner, how many need to be managed in an intensive care facility, and how many need long-term care for sequelae. A better understanding of patient management may help identify aspects of care, which could be optimized with the aim of limiting the burden of disease. In particular, this information could be of use for public health institutions to justify the interest of routine meningococcal vaccination programs. Large health insurance databases represent a useful source for collecting data on the clinical management of rare diseases such as IMD. 6] [17] [18] [19] [20] [21] [22] [23]  The national public health insurance database in France (Système National des données de santé; SNDS) is of particular interest in this respect as it covers >99% of the country's population (>66 million individuals) and thus allows exhaustive inclusion of all IMD cases in the country.
We have previously extracted data on all patients hospitalized for IMD in France over a six-year period (2012-2017), and reported on their characteristics and risk profiles, and the associated economic burden. 7, 23 n the present study, we have documented the care pathways of these patients before, during, and after hospitalization for the initial episode, including an assessment of the burden of in-hospital stays and complications requiring acute management during the index stay, as well as longterm sequelae of IMD.
Materials and methods This observational case-control study was conducted using the SNDS national health insurance database in France. The design and methodology of the study have been described in detail previously. 7 All individuals hospitalized between January 1, 2012 and December 31, 2017 with a diagnosis of acute IMD were defined as cases. The case definition was based solely on the presence of an ICD-10 code for IMD (A39. 0 to A39. 9; meningococcal infection) in the hospital discharge summary. This code explicitly requires the pathogen to have been formally isolated and identified. However, the results of the laboratory tests themselves (such as the serogroup) are not documented in the SNDS database. The index date for a case was defined as the date of first hospital admission. Three control subjects without IMD, randomly selected in the SNDS database, were matched to each case with respect to age, gender, and administrative district of residence.
Hospitalizations Information in the SNDS database was available for stays in general hospitals, rehabilitation centers, long-term facilities and psychiatric units. In this context, general hospitals correspond to hospitals dedicated to short-term stays in medical, surgical, or obstetric wards. In addition, home care coordinated from the hospital was also documented. The route of admission to a general hospital (referral by a general practitioner, visit to an emergency department, or transfer from another care facility) was documented. However, the specific reason for any consultation to a general practitioner or to an emergency department prior to hospitalization was not documented in the SNDS database. Any physician consultations in the three days prior to admission were identified. The period of three days was chosen, since this is the period over which symptoms of IMD can be expected to develop in the majority of patients.
Sequelae Certain medical conditions considered as potential sequelae of IMD were identified in the SNDS database for both cases and controls. Sequelae considered included immediate and irreversible events, such as amputation, which were identified from hospital discharge records and sequelae appearing and identified after discharge. The type of sequelae considered here followed the findings of a previous case-control study performed in the United Kingdom (UK) National Meningococcal Registry  26  and those of a Canadian meningococcal surveillance program,  27  completed by other sequelae reported in a recent systematic review of the subject. 11 equelae were identified in the SNDS database from hospital discharge summaries by the corresponding ICD-10-CM diagnostic code or CCAM (Classification Commune des Actes Médicaux) -a procedure code from the common classification for medical procedures used in France since 2005 -or from records of medication delivery in a community pharmacy.
The disease classification system developed in 2015 by the French national general health insurance fund was used to assign these medical conditions. 28 From the items extracted, sequelae potentially related to IMD were identified specifically using a previously described algorithm. 29 A list of codes used to identify individual sequelae is provided in Supplementary Table  S1. The conventions used in order to distinguish sequelae from comorbidities rely on the timing of the first occurrence with respect to the index hospitalization. 23 To qualify as sequelae, post-discharge medical conditions had to be documented in the SNDS database for the first time at a date after the index date. The SNDS database was searched during the year preceding the index IMD event to ensure that they were not already present before the event.
The relative risks of rehospitalization, recurrence, or developing sequelae in cases and controls were expressed as risk ratios (RRs) with their 95% confidence intervals (CIs). Mortality rates in cases and controls were compared using Kaplan-Meier actuarial survival analysis and compared using the logrank test. The findings are presented graphically as Forest plots. All statistical analyses were performed using SAS software, Version 9. 5 (SAS Institute, Inc. , Cary, NC, USA).
Ethics The study was conducted in accordance with the Helsinki Declaration of 1964, and its later amendments, as well as with relevant international and French regulatory requirements. Patient data on the SNDS database was anonymized using irreversible double encryption. Access to the SNDS is regulated by a Committee of Expertise for Research, Studies and Evaluations in the field of Health (CESREES), to which the present study protocol was submitted for approval. Since this study was retrospective on an anonymized database and had no influence on patient care, ethics committee approval was not required. The use of the SNDS database for this type of study is regulated by the French national data protection agency (Commission Nationale de l'Informatique et des Libertés), which approved the protocol.
27 [95% CI: 1. 12-1. 45]. 40 However, the one-year mortality rate (8. 3%) was comparable to the mortality rate during the index hospitalization in the present study. The mortality rates can also be compared with those reported in a similar recent study of a German medical insurance database. 15 he latter reported a mortality rate of 4. 3% at 30 days and of 5. 5% at 1 year. These rates are around twofold lower compared to the present findings from France. However, such a comparison should be interpreted with caution, since the German sample was considerably smaller (164 cases), with a different age distribution (and, potentially, a different serogroup distribution). Indeed, a report using exhaustive national surveillance data from Germany covering the period 2012 to 2015 estimated the case fatality rate at one year at 9.
6%. 41 The most recent English data (2019-2020) report a case fatality rate of 7% at the national level. 42 Finally, a meta-analysis of 48 national estimates published in 2019 found that case fatality rates ranged from 4. 1% to 20. 0% and provided a pooled estimate of 8. 3% [95% CI: 7. 5-9. 1]. 43 round one-quarter of all cases hospitalized for IMD developed long-term sequelae, which required specific management. Multiple sequelae were also frequent, documented in 298 cases (9. 2%). All of the medical conditions evaluated were documented significantly more often in cases than in matched controls, suggesting that they were indeed consequences of IMD, rather than spurious associations. The proportion of patients with sequelae (23. 3%) was very comparable to that observed in the German medical insurance database (23.
The strengths of the study include the large sample size, which is at the upper end of the range of cohort studies published to date. The SNDS database covers >99% of French residents, which is an important advantage compared to health insurance databases which are, for example, employment-based. 0] [51]  Countrywide databases such as the SNDS and the Danish National Hospital Register thus avoid recruitment biases due to socioeconomic factors. For this reason, the approach permits exhaustive capture of all sequelae presented by patients hospitalized for IMD using a standard methodology. The data collected could be of use to inform future epidemiological and economic modeling studies in France, which have, until now, had to rely on fragmentary data from different sources in other countries to document sequelae of IMD.
52 everal limitations of the study are inherent to use of the SNDS database. These include underreporting or potentially inaccurate reporting of diseases. This is unlikely to be a major issue for case identification, since the incidence of IMD matches that documented through mandatory surveillance monitoring in France  ,6  although it may well be relevant for certain complications or longterm sequelae of IMD. In this respect, certain sequelae previously identified in the UK IMD Patient Registry  26  could not be identified with confidence from the ICD-10-CM or CCAM codes due to a high risk of underreporting, namely separation anxiety and attention deficit hyperactivity disorder. Patients are rarely hospitalized for these disorders and, for this reason, they cannot be identified from the primary diagnosis listed on the hospital discharge summary.
According to registry and cohort studies,  26, [53] [54] [55]  mental health disorders are common in patients who have experienced an episode of IMD, and the fact that they are unlikely to have all been identified will probably lead to underestimation of the total number of cases with sequelae. In addition, the SNDS database does not contain information on the meningococcal serogroup, which may influence the severity, age distribution, and presentation of IMD. 34, 44 Severity, determined, for example, with a rating scale, is not documented, except through proxy variables such as admission to an intensive care unit. Furthermore, no information is available on when or how antibiotic treatment was initiated, which is a critical aspect of care in patients with IMD. 13, 56 Finally, other important and frequent consequences of IMD, such as cognitive impairment and lower educational achievement  26, 57  cannot be assessed in medical insurance databases.
Acknowledgments The authors would like to thank  Kinga Meszaros  ( GSK, Belgium ) for her participation in the scientific committee and involvement in the discussions and  Valérie Grange  ( GSK, France ) for her input during the development of the present manuscript. Joffrey Baneton  (Intys Consulting c/o GSK) assisted as operational and project manager during the conduct of the study. Medical writing support was provided by  Adam Doble  (Foxymed, on behalf of GSK). The authors would also like to thank  Business & Decision Life Sciences platform  for editorial assistance and manuscript coordination on behalf of  GSK. Lyes Derouiche (Business & Decision Life Sciences platform)  coordinated manuscript development and editorial support.
Gene and protein expression of ANGPTL2 during normal AoV development were detected in wild-type (WT) mouse embryos. We then show that knockdown of Angptl2 (Angptl2-KD) exhibited premature thickening of AoV leaflets at late embryonic stage during valve remodeling, associated with a dysregulation of cell apoptosis, senescence, proliferation, and by a decrease in Notch signalling, a key contributor of valvulogenesis. Adult Angptl2-KD mice, from the age of 2 to 10 months, develop AVS characterized by collagen disorganization and elevated trans-aortic gradient, without developing severe LV dysfunction or heart failure. In agreement with these data in mice, the expression of ANGPTL2 and NOTCH1 was elevated in human fetal semilunar valves and associated with pathways related to cell cycle and senescence.
1g, h ), as reported in the chick embryo  41. In accordance with our results, in situ hybridization of WT C57Bl/6 mouse embryos at E14. 5 from the public database Eurexpress (www. eurexpress. org)  46 shows expression of Angptl2 RNA in all four cardiac valves (Fig. S1 ). In addition, the spatial expression of ANGPTL2 in AoV leaflets during its development was assessed by immunofluorescence in cardiac histological sections from E14. 5 and E18 WT mouse embryos. At E14. 5, ANGPTL2 was expressed at the junction of the three leaflets of the PuV and the AoV (Fig. 1i ). Higher magnifications show that ANGPTL2 and CD31 are co-expressed in the cytoplasm of VECs in both the PuV (Fig. 1i ; 1) and the AoV (Fig. 1i ; 2). At E18, ANGPTL2 expression was also restricted to the border of the leaflet in the AoV (Fig.
5, leading to thickened AoV leaflets at E18 and further AVS in adult male and female mice (Fig. 5k ). ANGPTL2 is enriched in human fetal semilunar valves and associated with cell cycle and senescence pathways. Finally, we evaluated the expression of ANGPTL2 in human fetal and adult AoV by leveraging array data obtained in 16 valves (GSE45821)  57. Expression in 8 adult AoV (aged 19-55 years/old) was compared to fetal semilunar valves (gestational age 9-17 weeks). Genes with a fold-change >1. 5 at a false discovery rate >5% (FDR < 0. 05) were considered differentially expressed. In total, 2918 genes were upregulated in fetal semilunar valves, whereas 3028 genes were upregulated in adult AoV (Supplementary Data 1; Fig. 6a ). The expression of ANGPTL2 (log2 fold-change 1. 9, FDR = 1. 40E-07) was significantly upregulated in fetal semilunar valves.
Also, the expression of HEY1 (log2 fold-change 1. 8, FDR = 1. 55E-06) and NOTCH1 (log2 fold-change 1. 7, FDR = 3. 52E-06), two genes involved in cell fate and developmental pathways relevant to heart valve in human, were enriched in fetal semilunar valves (Fig. 6b ). In order to probe gene module expression and infer function, we carried out a weighted gene co-expression network analysis (WGCNA) by using gene expression retrieved from the human fetal and adult valves. WGCNA analysis identified 17 gene modules (Fig. S11 ). ANGPTL2 was a component of the turquoise gene module, which also included CDKN1A (p21), TP53, HEY1 and WNT3 (Supplementary Data 2). A pathway analysis of the turquoise gene module using the REACTOME dataset showed enrichment in cell cycle, signalling by Rho GTPase and cellular senescence (Supplementary Data 3; Fig.
In contrast to our data, a previous work demonstrated that Angptl2 knockout mice show enhanced cardiac function under steadystate conditions and resistance to the development of pressure overload-induced cardiac dysfunction  76. Discrepancies between these two mouse models may be explained by distinct genetic engineering favoring or not adaptive compensation, different substrains and age of the mice. Analysis of a human dataset revealed that ANGPTL2, together with members of the Notch pathway NOTCH1 and HEY1, were elevated in fetal semilunar valves compared to adult AoV. Moreover, WGCNA analysis identified ANGPTL2, CDKN1A (p21), TP53 and HEY1 as component of the same heart valve genetic module, and the REACTOME dataset showed their association with pathways related to cell cycle and senescence, reinforcing the hypothesis that ANGPTL2/Notch-mediated remodelling of semilunar valves can also occur in humans.
By exploring the public database Gene Expression Database (GXD)  80  at the Mouse Genome Informatics website (MGI; http://www. informatics. jax. org) which provides integrated data on gene expression in mouse, we found that Itgb1 (encoding integrin subunit β1), but not Itga5 (encoding integrin subunit α5) or PirB, is expressed in AoV at E13. 5 (MGI:5467139)  81  and E18. 5 (MGI:6306460)  82  , in the border of the leaflet, as also shown in the present study (Fig. 5i ). Our data also show that in fetal human AoV, both LILRB2 and ITGB1, but not ITGA5, were co-expressed with ANGPTL2 and members of the NOTCH signalling in the turquoise module (Supplementary Data 2). Interestingly, RNA-sequencing previously highlighted LILRB2 as a potential gene responsible for degeneration of BAV leaflets  83  , and our team previously reported that LILRB2 expression together with ANGPTL2 expression are upregulated in the valvular tissue of patients with calcific AVS  29.
LV iso-volumetric relaxation time was measured by sample volume-enlarged pulsed-wave Doppler. The average of three consecutive cardiac cycles was used for all measurements. Histological studies. Hearts (from E14. 5, E18, 2-and 7-month old mice) were embedded in OCT and sectioned at 7 μm intervals. Hematoxylin and eosin, Masson's trichrome, Alcian blue, Alizarin red, Oil-Red and Picrosirius red stainings were performed and imaged with an Olympus BX45 microscope. 20× and 40× magnitude pictures were taken. All quantifications were performed using ImageJ software, version 2. 0. Real-time qPCR. Total RNA was extracted from dissected aortic valve leaflets (from 4-and 10-month old mice) using RNeasy mini-kit (Qiagen) and reverse transcription was performed using the Moloney murine leukemia virus reverse transcriptase (ThermoFisher) according to the manufacturer's instructions.