dataesr/scientific-paragraphs-categorization huggingface dataset:
Identification of pregnancies that were terminated following a pre-natal diagnosis of a congenital anomaly was largely restricted to databases that captured induced terminations of pregnancy. The completeness and reliability of recording of congenital anomalies, along with the level of detail, may vary between databases and by specific type of anomaly. Within some databases, there is the opportunity to request additional non-coded data, full paper medical records or to send questionnaires that can help verify or refute diagnoses recorded in the coded data (Table  1 ). In addition to information on congenital anomalies, some databases were able to provide data on other adverse pregnancy outcomes such as prematurity, low or high birth weight and intrauterine growth retardation (Table  2 ).
Data on potential confounding variables Table  3  summarises the availability of data on potential confounding variables. Information on smoking status and alcohol intake was more commonly available in databases that captured data recorded in primary care,  1  Congenital anomalies are not recorded in the database itself; however, congenital anomalies can be identified via the North Netherlands EUROCAT registry. women other than the medicine specifically being evaluated as part of a study (maternal co-prescribing). None of the databases, however, captured data on medicines bought over the counter, which often includes standard-dose 0. 4 mg folic acid. As a result, information on folic acid exposure, which reduces the risk of some congenital anomalies when taken during the periconceptional period,  24, 25  was often restricted to women who received the higher 5-mg dose, which in most countries is only available on prescription (Table  3 ).
Availability of data on the indication for prescribing varied between databases. In the Norwegian prescription database, this information was available for all medicines that were reimbursed, although the level of detail on the indication has improved since 2009. In Denmark, some information on indication for prescribing could be inferred from hospital diagnoses prior to prescription. In the CPRD and SAIL, the patients' full medical records were available, and the indication for prescribing could be inferred from diagnoses recorded on or around the same date as a prescription for a particular product. No data on the indication for prescribing were available within the French, Italian or Dutch databases.
medicine use and safety during pregnancy For the UK and Danish databases, diagnoses of maternal comorbidities could be obtained from the same data sources as those used for the indication of prescribing. In Norway, however, information on chronic diseases that the woman had before pregnancy was recorded in the Medical Birth Registry. In France, only data on hypertension during pregnancy, gestational diabetes and pre-eclampsia were available. No data on maternal comorbidities were available within the Italian or Dutch databases, although for some chronic conditions, it may be possible to use prescription records as proxies. Recording of a family history of congenital anomalies was rare, and none of the databases captured information on maternal diet.
Sample size considerations One of the strengths of electronic healthcare databases is the large number of pregnancies they capture. Congenital anomalies are rare and arise from different embryonic tissues and at different gestational stages. As a consequence, the mechanism and timing of interference with embryogenesis will differ, and individual anomalies need to be considered separately, rather than amalgamated under a single all-embracing congenital anomaly category. 26 In addition, the exposures of interest may be relatively uncommon in pregnancy, and most medicines need to be evaluated individually, as often a 'class effect' cannot be assumed. 7 A classic example is the difference in teratogenicity of gluthetimide, which is not a major teratogen, and its derivative thalidomide. Both of these products are glutarimides, and both are hypnotics, yet their effects on the foetus are dramatically different.
27 The fact that congenital anomalies as well as exposures need to be considered at a granular rather than an aggregate level has considerable implications for the required sample size for evaluations of medicine safety in pregnancy. The large number of pregnancies captured within the electronic healthcare databases described in this study and the fact that the data are routinely collected make them a valuable tool for evaluating medicine use during pregnancy. For medicines that are new to the market or used to treat less prevalent conditions, however, even these large databases may be less capable than pregnancy exposure registries of capturing an adequate sample of exposed pregnancies during a particular period. 28, 29.
Exposure data The type of exposure data captured differed between databases, with the majority capturing prescription dispensing data whereas the UK databases captured all prescriptions issued. In France and Italy, only prescriptions reimbursed by the health service were captured. 4, 23, 30 One of the strengths of electronic healthcare databases is that prescription information is recorded prospectively and independently, by the prescriber or dispensing pharmacist, avoiding any maternal recall bias. 31 In addition, the level of detail available in terms of the specific product, the quantity and daily dose prescribed tends to be high, and these variables can often be used to calculate the duration and, hence, timing of potential exposure. Unlike exposure data obtained via a maternal interview, databases do not provide information on non-compliance and whether the patient took the medicine as directed.
The likelihood of exposure misclassification may be less of a concern for databases capturing dispensed prescriptions than those capturing all prescriptions issued, but, in addition, knowledge of the extent and type of prescriptions not captured in the database and the impact of these is important. In database research, exposure misclassification can also occur as the result of inaccurate information on the LMP date. Only six of the eight databases contained this information, or the gestational age at delivery, for the majority of pregnancies. The potential for exposure misclassification resulting from inaccuracies in the LMP date will be greater for products prescribed for short-term use (e. g. antibiotics) than for those used long-term to treat chronic conditions.
Outcome data In all databases, with the exception of the IADB. nl database in the Netherlands, it was possible to identify congenital anomalies. Unlike pregnancy exposure registries and case-control surveillance systems, which often have the benefit of review by a consultant paediatrician or teratologist and very detailed information on the specific congenital anomaly, electronic healthcare databases often lack detail on anomalies, and researchers may have to rely on the entry of a single medical code. In general, databases that include links to medical birth registries and congenital anomaly registers such as EUROCAT are likely to contain the most detailed information on anomalies, and it is an objective of the EUROmediCAT project to pilot the linkage between healthcare databases and EUROCAT congenital anomaly registries, where they co-exist.
An advantage of some of the databases reviewed was their potential for capturing induced terminations in addition to pregnancies ending in a delivery. This is particularly beneficial given that many of the more serious congenital anomalies may be diagnosed prenatally and may subsequently be terminated. If such anomalies are caused by a medicine, but not captured, the analyses would fail to identify an increased risk. Some databases in this review allowed the identification of clinically recognised spontaneous as well as induced pregnancy loss, premature birth, low or high birth weight and intrauterine growth retardation.
CONCLUSION Post-marketing surveillance systems are essential for evaluating the use and safety of medicines during pregnancy. This study suggests that, within Europe, electronic healthcare databases may be valuable sources of data that can provide information on medicine utilisation patterns, user characteristics and medicine safety during pregnancy. They may complement existing EUROCAT or case-control surveillance systems, especially where no pregnancy registry is in place. Given the potential of databases in the field of medication use in pregnancy, one aspect of the EUROmediCAT study will involve using the databases described in this paper to establish the extent and nature of use of antiepileptic drugs, antidiabetic medicines, asthma medicines and selective serotonin reuptake inhibitors during pregnancy in the different regions.
It will explore the relationship between users of the four drug groups previously mentioned and other health behaviours and exposures in order to identify possible confounders and effect modifiers in drug teratogenicity studies. The findings of the medicine utilisation studies will then be used to inform other aspects of EUROmediCAT, which are focussing on linking selected electronic healthcare databases to EUROCAT congenital anomaly registries to study the safety of these medicines when used during pregnancy.
, not available; ICD, International Classification of Diseases. *Secure Anonymised Information Linkage (SAIL) databank. † EFEMERIS database. ‡ The size of the population captured by the CPRD has grown steadily over time and was approximately 5. 0 million in May 2012. § The Child Health Database and Patient Episode Database capture the whole population of Wales (three million), whereas the General Practice Dataset currently contains around two million records. **Previously the General Practice Research Database (GPRD). † † Including only products reimbursed by the Italian National Health Service and excluding those dispensed to outpatients in a hospital pharmacy. ‡ ‡ Including non-GP prescribers working within the GP practice. § § For many databases, the data have become richer over time, and additional data sources have become available.
***The Danish National Prescription Registry has been collecting prescriptions since 1995, and the Birth and Patient registries of Norway go further back. † † † The Norwegian Prescription Database started collecting prescription data in 2004, but the Norwegian Medical Birth Registry has been collecting pregnancy outcome data since 1967. ‡ ‡ ‡ Opportunity to review against charts and to request further information via questionnaires. ****Opportunity to request linkage to other datasets. † † † † Opportunity to request further information only for medical abortions. r. a. charlton et al.
ACKNOWLEDGEMENTS The authors would like to acknowledge all the data providers who made anonymised data available for research. The work presented in this paper describes anonymised data held in the SAIL system, which is part of the national e-health records research infrastructure for Wales, and the authors also thank  David Tucker ,  Martin Heaven ,  Daniel Thayer ,  Karen Tingay  and  Leila Pinder  for their contribution to the work carried out with SAIL data. This paper also describes data from the Full Feature General Practice Research Database obtained under licence from the  UK Medicines and Healthcare Products Regulatory Agency. However , the interpretation and conclusions contained in this report are those of the authors alone. The Tuscany Registry of Birth Defects is funded by the  'Direzione Generale Diritti di cittadinanza e Coesione sociale-Regione Toscana.
'The  Emilia-Romagna Registry of Birth Defects  is funded by the  Emilia-Romagna Region Health  authority grant number  Delibera 56412/ 2010. The EFEMERIS Database is funded by  Agence Nationale de Securité du Médicament ,  Caisse Nationale d'Assurance Maladie des travailleurs salariés ,  Programme Hospitalier de Recherche Clinique (PHRC). Financial support for this study was provided by the  European Union  under the  7th Framework Programme  (grant agreement  HEALTH-F5-2011-260598 ).
‡ ‡ All medical abortions (CDA database) but only induced abortions performed in the University Hospital (CHU) of Toulouse (PMSI database). § § Compulsory notification of those occurring from 12 weeks' gestation although some underreporting especially for those occurring at less than 16 weeks. ***Only women followed in the University Hospital of Toulouse (PMSI database). † † † § § § At 9 and 24 months.
MATERIAL AND METHODS Project proposal development A detailed project proposal describing the background, project procedures, study questionnaires and forms to capture participant data and details of investigations, the project database, quality assurance methods and means of monitoring and evaluation were jointly developed between June 2010 and March 2011 by the National Cancer Institute (NCI), Bangkok, Thailand, and the provincial health authorities with technical assistance from the Screening Group of the International Agency for Research on Cancer (IARC) of the WHO, Lyon, France. Following the finalisation of the project proposal, its approval by national authorities and completion of training for the providers, screening started in April 2011 and recruitment of eligible participants was closed in November 2012.
Colonoscopy Colonoscopy was provided to iFOBT-positive individuals on scheduled days every week at the Lampang Regional Cancer Center. A second informed consent was obtained from people undergoing colonoscopy, biopsy and treatment. The outcome of colonoscopy was reported as normal, polyps, suspected cancer or invasive cancer. Polyps and small lesions were removed and subjected to histopathology. Large lesions were biopsied for histological assessment. Those diagnosed with CRC received further investigations for clinical staging and treatment as per the standard protocol developed in Thailand. The findings of colonoscopy, any severe adverse events within 30 days following colonoscopy (such as bleeding, perforation, administration of blood transfusion, hospitalisations for severe abdominal pain, paralytic ileus, cardiovascular events, hypotension, syncope, shock, dehydration, anaphylactic reactions, cardiorespiratory arrest, etc), histology, stage, treatment and follow-up assessment were recorded in a diagnosis and treatment form and were entered into the database.
Data management, monitoring and evaluation Personal identification (name, age, address and citizen ID number), sociodemographic information, screening test result, results of colonoscopy and other investigations, treatment details and follow-up information were collected in specifically developed forms and entered in a multiuser programme database with inbuilt validation checks called CRCreg developed by the IARC. The database was continuously updated as the pilot project progressed. It is possible to link the screening programme and the cancer registry databases using the unique citizen ID numbers, which will enable the identification of false-negative cases and interval cancers. The study database was analysed to document participant characteristics, participation rates for screening and test positivity rates by sex, age, the district of residence and the proportion of test-positive individuals complying with referral for colonoscopy, colonoscopy results, final diagnosis, stage of invasive cancer, treatment details and adverse events.
Unfortunately, we could not exactly quantify the proportion of participation from home visits or by visits to the PCUs/CHs as this was not documented in the database. The higher screening uptake in rural populations than in urban areas suggests that more direct person-to-person contacts and personalised invitations and personalised delivery of collection kits improved the participation. A personalised approach to participant recruitment has also been reportedly associated with a higher uptake of CRC screening in other settings. 26 A higher participation in rural populations than in urban and metropolitan populations has been reported from other countries as well. 26 28 Higher participation for colonoscopy among the low-income and rural population reflects the faith and dependence of the socioeconomically weaker sections on public health services than those with higher incomes and living in urban areas.
Hypoxylon with regard to its stromatal pigments  (Quang et al. 2005 ). Indeed, molecular data based on α-actin and β-tubulin genes were in accordance with morphological and certain chemotaxonomic traits, which resulted in the erection of the genus Annulohypoxylon  (Hsieh et al. 2005 ). In the same study, H. placentiforme was transferred back to Daldinia, even though the stromata of D. placentiformis do not show conspicuous concentric zones. The molecular data based on α-actin and β-tubulin sequences reported by  Hsieh et al. (2005)  clearly revealed affinities of this species to Daldinia. Recently, these phylogenetic relationships were confirmed based on chemotaxonomic and ITS rDNA sequence data  (Bitzer et al. (2008). Several polyphasic studies using chemotaxonomic, morphological, and molecular data were meanwhile undertaken to verify the affinities of the cleistocarpous genera of the Xylariaceae.
On the other hand, the genus is known to be extremely diverse with respect to its secondary metabolism, and the discovery of many unprecedented compounds can still be expected. In this context, it should be mentioned that since reliable molecular data on the most common Daldinia spp. have become available, reports on new chemical compounds have been increasingly associated with rather sound molecular identification methods. Albeit no details on the morphology of the respective producer organisms did accompany the respective publication of chemical data, the compounds reported were chemically rather similar to the known metabolites of Daldinia, and high degrees of homology of 99 % of the nrDNA sequence data to those of well-characterised reference specimens, would suggest that at least the species group has been correctly identified.
placentiformis), based on molecular data  (Hsieh et al. 2005)  and this procedure also appears justified from a comparison of phenotype-based characteristics, because its characteristic secondary metabolite profiles (cf. Bitzer et al. 2008 ) and cultural morphology are reminiscent of the D. eschscholtzii complex, rather than of a Hypoxylon. All Daldinia species so far examined initially show fairly rapid growth, colonising the agar from the inoculum point at the centre by non-differentiated, whitish hyphae. These hyphae soon form a felty, azonate mycelium and become greenish in patches (cf. D. clavata in Fig. 5J  and D. lloydii in Fig. 8C ), finally turning Mouse Gray (118). These patches indicate the melanisation of hyphae and often give rise to the characteristic stromatic structures that are rather typical of Daldinia and related genera, but do not normally develop into conidiophores.
palmensis  (Stadler et al. 2004a). In this study, several Nodulisporium spp. could be assigned to members of the genus Daldinia, since a comparison of morphological, molecular and chemotaxonomic data with cultures derived from well-studied teleomorphs leave no doubt as to their identity. However, this was only accomplished because the HPLC profiles left no doubt that they belong to Daldinia and allies, rather than to Hypoxylon or Annulohypoxylon, and type strains were extant that could be studied for their molecular phylogeny. In all likelihood, there are also numerous species of anamorphic daldinoid and hypoxyloid Xylariaceae, which, not unlike other Ascomycota, have abandoned the production of the teleomorph altogether. In addition, from the morphological descriptions of the known Nodulisporium spp.
In some cases, the corresponding HPLC-UV and HPLC-MS spectra are shown as well. Since two different gradient systems and stationary phases were employed and standards of numerous (known and yet unidentified) pure secondary metabolites were available for comparison, the identification was based on two datasets of spectra and retention times and allowed for unambiguous identification of known compounds in most cases. Spectral and chromatographic data of yet unknown components were saved in a HPLC library that may allow for their future identification, or for similarity analyses that are not based on their chemical structures.
During alignment of the sequence data of ca. 600 representative Xylariales (retrieved from GenBank, own unpublished data and sequences published first here), we noted that the resolution of the phylogenetic tree was highly dependent on the taxon selection, which greatly influenced the percentage of reliably alignable data. Finally, most taxa of xylarioid Xylariaceae (i. e. , genera with geniculosporium-like anamorphs like Xylaria, Kretzschmaria, Nemania, and Rosellinia; cf. Fournier et al. 2011)  were omitted, since their ITS regions sequences were found to contain too many DNA portions that could not be aligned with certainty. The tree was rooted with Calceomyces lacunosus, and Graphostroma platystoma and Biscogniauxia nummularia were included as additional outgroup taxa. These fungi all show morphological characters that are regarded as basal in the Xylariaceae (e.
concentrica, D. loculata and D. vernicosa from different geographic regions and host plants were selected. A list of all specimens studied is given in the Results Section (Molecular Phylogeny chapter). This list also includes sequence data retrieved from GenBank and the respective references. Special care was given not to retrieve unreliable reference data, where it was not clear whether the material was correctly identified and deposited in a public domain collection. Phylogenetic reconstruction. Double-stranded sequences of the ITS region (ITS1, 5. 8S rRNA gene, and ITS2) were obtained and further processed as outlined earlier  (Triebel et al. 2005 ). The final alignment included 158 sequences, throughout which 381 positions  were alignable with certainty (positions 33-62,  99-101, 105-132, 143-368, 386-437, and 443-461  according to AY616683, derived from D.
Daldinia vernicosa ≡ Sphaeria vernicosa Schwein. , J. Acad. Nat. Sci. Philadelphia 5: 9. 1825; non DC. & Lam. [: Fr. ]. 1815; nec Fée, 1834. ≡ Hypoxylon vernicosum (Schwein. ) Berk. & M. A. Curtis in Berk. , J. Linn. Soc. , Bot. 10: 384. 1869 , non Ellis & Everh. , 1897. Holotypus: USA, North Carolina, Salem,  Syn. 1175 (PH). Epitype (here selected): MBT177384; Germany, North Rhine, Westphalia, Wuppertal, burnt Fagus sylvatica, 31  Aug. 1996 , H. Wollweber, Ww 2899 (KR 0026318, duplicates in K and herb JDR, culture BCRC 34048, GenBank Acc. Nos of DNA sequences: AY951697, AY951809, and EF026146; see  Ju et al. 1999 and Hsieh et al. 2005 ). = Lycoperdon atrum Schaeff. ,  Fung. Bavar. Palat. 4: 131. 1774. -nom. inval. (another valid name cited as synonym). = Daldinia fissa Lloyd, Mycol. Writ.
Daldinia hausknechtii A Daldinia loculata differt in ascosporae maiorae, angustiorae, irregulariter ellipsoidae-inequilaterales, apicibus angustatis vel rotundatis, usque at 13-16 × 7-8 µm. A Daldinia loculatoides differt ascosporae minorae. Holotypus: France, La Réunion (Indian Ocean), Saint Paul, le Maïdo, 2200 m alt. , substrate not documented, 27  Mar. 2005, A. Hausknecht (WU 26501, ex-type culture CBS119995, GenBank  Acc. No. JX658521). Known distribution: So far only known from the type collection in La Réunion; unknown host. Teleomorph: Stromata hemispherical with a short stout stipe to depressed-spherical and sessile, with slightly exposed perithecial outlines, 1-2. 7 × 1-1. 5 cm; surface Sepia (63) to Dark Brick (60), blackening where outer pruina is worn off; dull reddish brown granules immediately beneath surface, with KOH-extractable pigments Vinaceous Purple (101); tissue between perithecia grey brown, pithy; tissue below perithecial layer composed of alternating zones, darker zones brown, pithy to woody, 0.