dataesr/scientific-paragraphs-categorization huggingface dataset:
2006). So far, only one study has addressed sex differences in brain anatomy related to RRBIs, on the ABIDE dataset assessing 25 females and 25 males with ASD. The authors reported that gray matter of motor regions could discriminate boys from girls with ASD  (Supekar and Menon 2015). In addition, only in girls RRBIs were related to increased gray matter of the motor cortex, the supplementary motor area and Crus 1 subdivision of the cerebellum, while correlating with the right putamen in boys  (Supekar and Menon 2015). These findings indicate a different relationship between brain anatomy and RRBIs for males and females with ASD, thus potentially pointing to divergent etiological pathways to inflexible behaviors between the sexes. More generally, ASD is associated with environmental, shared and non-shared, as well as genetic components which likely contribute to the heterogeneity in the etiology  (Hallmayer 2011; Sandin et al.
Meshes were constructed for gray and white matter out of approximately 150,000 vertices per hemisphere, then parcellated according to the Destrieux Atlas  (Destrieux et al. 2010). Next, mean cortical thickness, volume and surface areas were obtained for each region in each hemisphere. Whole brain volume from FreeSurfer was used as a covariate in all surface-and volume-based analyses except for cortical thickness, because cortical thickness is less related to brain volume  (Toro et al. 2008). After a quality control of the brain data processed from an initial 261 subjects that had completed MR scanning, 150 participants with three outputs each (cortical volume, surface area and cortical thickness) were retained in the final surface-based analyses. Quality control was done by visual inspection of the T1 images for presence of movement errors, accuracy of skull stripping, and accuracy of the FreeSurfer segmentation, i.
e. inspecting if the pial and white matter surfaces accurately followed the intersection between brain/CSF and gray matter/white matter respectively. Minor segmentation errors, such as at the temporal poles, were tolerated, in particular with regard to the young age of the subject group. Subjects were given a score on movement and image quality, of 1 (no errors) -4 (very severe movement), and only subjects with a score of 1 or 2 were included. Within pairs, RRBI's (ADI-R) did not predict data quality (B=0. 009, p=0. 814) or movement scores (B=-0. 009, p=0. 889). Volume-based cerebellar analysis: Gray and white matter regional volume  (FSL)  Volumes of cerebellar white and gray matter were retrieved using volume-based morphometry. The 261 raw brain volumes were intensity normalized and the brain was extracted using AFNI's 3dskullstrip.
Skull stripped 3D images were segmented in 3 tissue types (Gray Matter-GM, White Matter-WM, Cerebral Spinal Fluid-CSF) using FAST (FMRIB's Automated Segmentation Tool within FMRIB's Software Library) which also corrects for spatial intensity variation. Segmented images were warped to MNI space using non-linear registration FNIRT from FSL. GM and WM volumes for the somato-motor cerebellar region were extracted from the intersection between the somato-motor regions in Buckner's 7-network functional atlas  (Buckner et al. 2011 ) and segmented individual volumes using a custom script in C. The same 150 individuals that had passed the surface-based quality control were included in the volume-based analyses. These 150 scans all had good segmentation quality in FSL, because the inclusion decision was based on the surface-based segmentation, which was more sensitive to quality of raw images.
g. genetic factors, demographics etc. ). MZ and DZ twins were collapsed in order to increase statistical power. Within-twin pair associations were estimated using a conditional linear regression model within the generalized estimating equations (GEE) framework, using the drgee package from R  (Zetterqvist and Sjölander 2015). Herein, the difference in the exposure variable within a pair is correlated to the difference in the outcome variable within the same pair. A within-pair association was estimated by correlating the difference in the exposure variable to the difference in the outcome variable within a pair (see Supplementary fig. 2  and 3  for some examples). This within-pair relationship is calculated for all pairs resulting in an estimate for the average within-pair association between RRBIs and brain anatomy in the group.
Acknowledgments Firstly, we are grateful for the participation, time, patience and cooperation of our twins and their parents in the  RATSS  project and especially during the scanning sessions. Secondly, we would like to thank all the colleagues and professionals involved in this big project for their help in collecting the data but also their advices and contributions, namely  Charlotte Willfors ,  Kristiina Tammimies ,  Anna Lia Sacerdoti ,  Kerstin Andersson ,  Anna Lange Nilsson ,  Johanna Ingvarsson ,  Elin Vahlgren ,  Elzabieta Kostrzewa ,  Johan Isaksson ,  Martin Hammar ,  Christina Coco ,  Anna Råde ,  Lina Poltrago ,  Steve Berggren ,  Eric Zander ,  Andreas Fällman ,  Therese Lindström ,  Anna Lövgren ,  Torkel Carlsson ,  Soheil Mahdi  and  Lynnea Myers. The study was funded by the  Swedish Research Council, Vinnova ,  FORTE  (previously called FORMAS), the  Swedish Brain foundation (Hjärnfonden) ,  Stockholm Brain Institute, Autism and Asperger Association Stockholm, Queen Silvia Jubilee Fund ,  Solstickan Foundation ,  PRIMA Child and Adult Psychiatry , the  Pediatric Research Foundation at Astrid Lindgren Children's Hospital ,  Sällskapet Barnavård, Jerring Foundation , the  Swedish Order of Freemasons, Kempe-Carlgrenska Foundation ,  Sunnderdahls Handikappsfond, Gålöstiftelsen , the  Innovative Medicines Initiative Joint Undertaking  (grant agreement number  115300 ), which comprises financial contribution from the  European Union 's  Seventh Framework Programme  (FP7 /2007 -2013) and in-kind contributions from companies belonging to the  European Federation of Pharmaceutical Industries and Associations (EU-AIMS ).
Appropriate access and use of the validated instruments (original and translations) Easy, centralized, and appropriate access to original instruments and their translations is often a prerequisite to efficient research. With a unique point of access endorsed by the developers of instruments, researchers are able to access and use the original instrument and its translations  48. The centralization and control of access also enables the integrity of the each measurement instrument (original and translations) to be respected  49. Once the instruments are fully developed and validated (Steps 1 and 2 on Figure  1 ), they are made publicly available through the Patient-Reported Outcome and Quality of Life Instruments Database (PROQOLID™)  50  , managed by Mapi Research Trust and part of the ePROVIDE™ web platform (https://eprovide.
mapi-trust. org/). To get access to the instruments distributed on ePROVIDE™, each new user has to complete a free registration form at https:// eprovide. mapi-trust. org/login (click to the Free Registration button). The following link leads to a tutorial to help navigating through the whole registration process: https://eprovide. mapitrust. org/tutorials/registering-for-free. Once the registration is completed, the register button will lead the user to his/her free ePROVIDE™ account. From there, any retrieval of instruments can be performed. Instruments and their respective user manuals can be retrieved through the main search engine of the database by using either the full name or parts of the name (e. g. , ABOUT™-Perceived Risk, Perceived, or Risk) or within the "Our Catalog" section of ePROVIDE™ (https://eprovide.
Acknowledgements The authors would like to thank the following individuals for their participation in the development of the ABOUT™ Toolbox:  • Patricia Binggeli ;  Emilie Clerc , B. S. ;  Sophie Gallot , M. S. ;  Frank Lüdicke, M. D. ; Pierpaolo Magnani ;  Antonio Ramazzotti ; and  Steve Roulet  at  Philip Morris International • Vanessa Brunel ;  Jeremy Lambert, Ph. D. ; and  Celine Marcuccilli at Mapi , an  ICON  plc  Company • Thomas Alfieri, Ph. D. ; Mark Atkison , M. S. ;  Stephen Crawford, Ph. D. ; and  Marie Martin, Ph. D. , at  Covance Market Access Services ,  Inc. • Karl Fagerström, Ph. D. , at K. Fagerström Consulting AB.
Data collection: Study design Targeted population, geographic areas and period. Targeted population: We identified all the stakeholders involved in the Sylvatub system, and assigned them to three categories, according to their role in the surveillance system. The first category "collectors" corresponds to those working at the front line in the field, such as hunters for EC-SSC and PSURV-SSC, trappers for badgers in PSURV-SSC and the technicians of the SAGIR network for SAGIR-SSC. The second category "coordinators" corresponds to those coordinating surveillance activities: local federations of hunters, local federations of the ONCFS, "lieutenants de louveterie". The third category "officers" corresponds to those representing the state, such as the local veterinary services. Geographic areas: We took into account the level of risk, which may influence the experiences of each category of stakeholders, thereby affecting their perception of the utility of the Sylvatub system and its acceptability, by conducting this study in four different départements (French administrative areas essentially equivalent to counties).
In qualitative approaches of this kind, sample quality is more important than sample size  [7, 15] , as the objective is to maximize the diversity of situations and, thus, of data collected as points of view. The ideal number of interviews is considered to have been reached when no new information is collected, which is called the theoretical saturation  [16, 17]. Participants were first contacted by phone and informed about the study. Semi-structured interviews were conducted individually, face-toface, at a location of the participant's choice. This method has the advantage of being standardized with the use of guidelines for the interview developed by the authors (S1 File), but it is also flexible as participants were encouraged to provide any additional information they considered relevant, and can be used to collect both opinions and information about attitudes.
Acknowledgments We would like to thank all the hunters, their local representatives (hunters' federation), the technicians of the SAGIR network and their local representatives, the trappers and lieutenants de louveterie, the veterinary officers and the national coordinator, for their time and insight, which were essential for this study. We also thank  Eric Durand , who participated in data collection at local level. Finally, we thank  Julie Sappa  from the Edelman association, for the English proofreading of the manuscript.
Introduction The clinical management of cystic fibrosis (CF) has long been of paediatric dominance. In the 1940s and 50s, when knowledge of the disease pathogenesis and availability of treatments were scarce, few patients entered adulthood  [1]. Today this is no longer the case. In many countries, children account for less than half of the CF population, with the focus and burden of care gradually shifting towards adult care. This partly results from the understanding that the clinical spectrum of CF is wider than originally believed and the greater diagnostic consideration of phenotypes presenting in adulthood. However, there is no doubt that the outstanding attainments in survival predominantly stem from improvements in care. The establishment of multi-disciplinary centres, creation of large epidemiological datasets, emphasis on early diagnosis, together with important new treatments originated by dynamic pre-clinical and clinical research, have all been instrumental in the evolution of terrific care.
4. 2. What are the diagnostic criteria for CF?  [17, 18]  A positive NBS test result or clinical features suggestive of CF, including, but not restricted to, diffuse bronchiectasis; positive sputum cultures for a CF-associated pathogen (especially P. aeruginosa); exocrine pancreatic insufficiency; salt loss syndrome; and obstructive azoospermia in males and a sweat chloride N 59 mmol/L and/or two CF causing CFTR mutations in trans  2 The term "mutation" is referred as a "pathogenic variant", according to the CFTR-2 database (http://www. CFTR2. org). For mutations not characterised by CFTR-2, other evidence may be considered, such as bibliographic data and other genetic databases (also see paragraph 4. 6), all requiring accompanying sweat chloride confirmation. a. The laboratory should be able to reliably extract DNA from dried blood spot samples, whole blood (EDTA) or buccal swabs.
b. Samples should be analysed on a weekly basis to avoid significant delay. c. The laboratory should partake in an external quality assurance exercise with at least annual certification. d. The primary laboratory should be able to provide a limited CFTR mutation panel as a starting point that recognises at least one abnormal allele in N96% of the individuals with CF in the local population  [22]. e. When only one mutation is recognised, extended exon DNA analysis (gene sequencing) should be available in the primary laboratory or a secondary laboratory to detect rare mutations and major deletions or duplications should be sought. The disease liability of variants detected by DNA sequencing should be validated against the CFTR-2 database. f. Novel mutations or variants should be reported to locus specific databases in order to facilitate future interpretation of variants of unknown clinical significance.
Acknowledgements  Jeannette Dankert-Roelse ,  Silvia Gartner ,  Barry Linnane ,  Sarah Mayell ,  Dorota Sands ,  Olaf Sommerburg , ( ECFS Neonatal Screening Working Group Core Committee );  Dominique Pougheon-Bertrand ,  Martin Stern ,  Gilles Rault ,  Romana Laušerová  ( ECFS Standards of Care Working Group );  Jacquelien Noordhoek ,  Hilde De Keyser  ( CF Europe );  Emmanuelle Boulandet ,  Genetician (Paris, France) ;  Cornelis K van der Ent  ( ERN-LUNG, CF Core Network );  Tessa Vuister  and  Chloe Fisher ,  Clinical Psychology Interns (Leeds, UK).
d. An early follow-up appointment with the CF physician and the CF centre staff should be arranged to assess understanding (no more than one week). Contact information of the CF Centre should be given. The diagnosis of CF is confirmed in patients with two CF-causing mutations identified in trans and classified in the CFTR-2 database (https://www. CFTR2. org) or other relevant information base. However, the absence of two CF-causing mutations after extended DNA testing in the presence of typical clinical or laboratory features of the disease, or abnormal CFTR bioassays (see paragraph 4. 10), does not rule out CF. b. Patients with "mutations of varying clinical consequence" require further evaluation in a Specialist CF Centre. Those include the mutations that result either in CF or in a CFTR-related disorder such as diffuse bronchiectasis, congenital bilateral absence of vas deferens (CBAVD), recurrent/ chronic idiopathic pancreatitis.
Vears et al. [29]  propose points to consider to laboratories offering diagnostic genome analysis. In line with the EG-ESHG guidelines  [10] , they also support the view that laboratories do not have an obligation to routinely reanalyse data but rather in response to a specific request initiated by the patient or their clinician. However, if the information on reclassification of a given variant becomes available to the laboratory, then it would be considered good clinical practice for those laboratories to identify patients carrying that variant from their database and issue a new report to the original referring clinician  [29]. It is also worth noting that, in the wider context, laboratories might have different rules in reporting, such that at present there is inconsistency, not only concerning whether or not a VUS is reported, but also sometimes on variant classification, even using the same guidelines for interpretation.
El Mecky, Johansson et al. (personal communication) undertook an online focus group of all clinical genetics laboratories in the Netherlands to discuss their current practice and views about future practice regarding the reclassification of variants, as well as which reclassifications are communicated from laboratory to clinician. Preliminary results indicate differing views on which reclassifications merit recontacting from laboratory to clinician. Furthermore, no systematic approaches exist for laboratories to actively reinterpret variants (i. e. periodically reviewing new evidence on genetic variants in the laboratory's database, unprompted by patient or clinician), but some participants desired to implement such procedures. The UK study  [11, 15]  reports a lack of agreement between genetic HCPs and clinical scientists in the laboratory about whose role it should be to monitor the changing interpretations of variants so that appropriate recontacting can be triggered.
Electronic medical records, genetics laboratory databases, and patients' registries, all represent powerful tools to identify, monitor and reach patients who might benefit. The genetics laboratories are the first repositories of the variants which might be reinterpreted over time, and as such the ideal point of departure for triggering recontact through the referring clinicians. Centralization of laboratory facilities and their collaboration with data sharing tools and curated databases might simplify this process. Professionals' and patients' associations can also substantially contribute in updating HCPs and patients with new, relevant information on specific conditions, and facilitating the recontact. While identifying different stakeholders in sharing responsibility to recontact, including patients, genetic and non-genetic HCPs, and lab specialists, such shared responsibility should be seen as a pragmatic way forward until best practices have been identified.
The allocation of dedicated resources for activities on recontacting should be considered Sustainable and equitable recontacting cannot be achieved without suitable informatics tools, appropriately set up. Ideally these should be integrated into the Electronic Clinical Records and the databases of diagnostic genetics laboratories. Implementation of patients' registries also represents a powerful tool. Resources should be allocated for research on recontacting procedures. Research is needed to further understand recontacting activities and how they could best be organised, including research on HCPs' activities and development of informatics tools.
Data sharing should be promoted The centralization of laboratory facilities, progressive adoption of data sharing tools and of curated databases might support and simplify both the re-interpretation of VUSs and the implementation of the recontacting process. An open dialogue to promote patient and public engagement and enhance recognition of the importance of data sharing, explaining the clinical utility of whole exome/ genome sequencing approaches, as well as their complexities, will be instrumental in developing these systems for the benefit of the patients and their families.
Acknowledgements The authors thank the persons who took part in earlier discussions on these Recommendations, especially the members of the  Public and Professional Policy Committee of ESHG , and persons who commented on earlier versions:  Julia El Mecky ,  Lidewij Henneman ,  Marleen Jansen ,  Lennart Johansson ,  Francesca Mari ,  Katherine Payne ,  Chris Patch ,  Angela Peron ,  Alessandra Renieri ,  Nikolaus Schlaich ,  Asbjørg Stray-Pedersen ,  Danya Vears  and  Helger Yntema. PPPC members in 2016-2018 were  Caroline Benjamin ,  Pascal Borry ,  Angus Clarke ,  Christophe Cordier ,  Martina Cornel  (Chair),  Carla van El (Secretary General) ,  Florence Fellmann ,  Francesca Forzano  (Co-chair),  Heidi Howard ,  Hülya Kayserili , Béla.
Acknowledgments The authors would like to thank the  French Government for the "Investments for the Future" LABEX ICST  #  ANR-11 LABX 0015. This work was supported by the  Centre National de la Recherche Scientifique  and the  Agence Nationale de la Recherche  ( ANR-13-SAMA-0001  and  -0002  and  ANR-13-RPIB-0001  and  -0002 ). We would like to dedicate this work to  Morgane Roulot , our great friend and colleague. She is still greatly missed by all of us.
When a fluid challenge (FC) was decided by the senior in charge, it was calibrated to investigate the relationship between systemic and cerebral hemodynamics. The FC consisted in a rapid infusion of 250-500 ml of crystalloids over 5-10 min. Data were collected exclusively in patients who exhibited a positive FC response defined as an increase in SV of at least 10%. Among them, those who exhibited an increase in MAP above an arbitrary limit of 5% were called responders-responders (RR = SV increase > 10% + MAP increase > 5%). When MAP increased less than 5%, these patients were called responders-non-responders (RnR = SV increase > 10% + MAP increase < 5%). Following exclusion criteria were used: increase in SV < 10%; age < 18 years; pregnancy; unstable hemodynamics or absence of sinus rhythm; absence of a window for TCD measurements; previous diagnosis of neurological or psychiatric disorders.
Data collection The collected clinical characteristics were: age, gender, administration of sedative and vasopressor agents, Charlson comorbidity score, cardiovascular comorbidities especially hypertension, reason for admission, origin of sepsis, severity of the critical illness assessed by SAPSII score at admission, SOFA score at inclusion. In addition, ETCO 2 (mmHg), PaCO 2 (mmHg), natremia (mmol l -1 ), glycemia (mmol l -1 ), and temperature (°C) were monitored and collected during the protocol time. The investigator obtained the following hemodynamic parameters just before and after the FC: SAP, DAP, MAP (mmHg), heart rate (HR, min -1 ), CO (l min -1 ), and SV (ml/b). The trained investigators measured the transcranial Doppler blood flow velocities in both side middle cerebral arteries (MCAv) using pulsed Doppler velocimeter (Transcranial Doppler, Athys ® , France Lyon).
Seroprevalence study in Kara town, Togo A cross-sectional seroepidemiological study of the general population with one study visit per participant was performed in Kara during October 2009. Volunteers were recruited from the general population of Kara town, capital of Kozah district, the area experiencing the MenX outbreak during March 2007  [8]. Based on the presumption that seroprevalence varied by age, the study included healthy volunteers in three age strata: children aged 3-5 year (aged at least 1 year old during the outbreak season of 2007), teenagers (13-19 years of age) and young adults (20-25 years of age). In the absences of any pre-existing serological data on capsular group X, a sample size of 100 participants per age group was chosen for study feasibility. This samples size would provide prevalence estimates with 95%-confidence intervals allowing a precision of ±5 to ±9.
Controls from Burkina Faso and the United Kingdom Control sera were obtained from previous seroprevalence studies carried among healthy individuals aged 1-29 years in Bobo-Dioulasso, Burkina Faso in 2003  [24]  and 2006  [25] , which used a similar protocol for population sampling and data collection. A subset of these, with similar age distribution as the Togolese samples, were randomly selected and served as African controls from an area with limited or no MenX disease. Sera were primarily from the 2006 study, and from the 2003 study if none age-matching sera were available from the 2006 study. Burkina Faso, which is bordering Togo to the north, is entirely within the meningitis belt and had never any MenX outbreak documented by the time of collection of the serum samples in this study. However, a serogroup A outbreak was ongoing during sample collection in 2006.