dataesr/scientific-paragraphs-categorization huggingface dataset:
9, 15, 18 The literature search was an update to a therapeutic review conducted by CADTH in February 2015, which was further expanded by PHAC to include PubMed and ClinicalTrials. gov to November 2015. Prepublication searches were conducted to update both reviews. The literature search for the screening review and its grey literature search were updated to Dec. 11, 2016. The literature update for the treatment review was updated to Nov. 21, 2016, but was limited to randomized controlled trials (RCTs) published in MEDLINE, Embase and the Cochrane Library. The Knowledge Translation group of St. Michael's Hospital (Toronto, Ontario) engaged members of the public on behalf of the task force at two stages of the guideline development process. 19, 20 For phase one, 19 participants from the HCV screening and treatment populations rated outcomes to be included in the systematic reviews, using two online surveys and a focus group.
Working group members identified five HCV experts, three of whom provided parameter estimates and ranges and the location of possible supplemental data supporting their estimates. Parameter estimates were established by calculating the mean value of the responses that the experts provided. The latest prevalence estimates from PHAC (2014) were used as inputs for the model for the general population and various subgroups. 1, 21  The Feasibility, Acceptability, Cost, and Health Equity (FACE) tool was used with organizational stakeholders to gain their perspective on the priority, feasibility, acceptability, cost and equity of the recommendation. 22  The FACE survey was pilot-tested with this guideline as part of a validation exercise. Stakeholder organizations that provided input on the recommendation using the FACE survey are listed in Appendix 3 (available at www.
g. , specific comorbidities), only wealthier individuals or those with private insurance would obtain earlier access to treatment not currently funded by government; 4) the unknown magnitude of benefit of treatment on reducing risk of transmission; and 5) the very large impact that screening and treatment would have on health care budgets, and associated opportunity costs (i. e. , the limit this would place on the ability to provide other health care interventions that would have to be forgone for lack of funds, despite being supported by better evidence). Indirect evidence showing that new DAA-based treatment is much more effective in achieving sustained virologic response than older pegylated interferon-ribavirin treatment regimens was also considered in developing this recommendation. As such, emerging evidence on new treatments with similar effectiveness would not change this recommendation.
Acknowledgements: We are grateful to  Prinon Rahman  and  Olga Milliken  of the  Global Health and Guideline Division at the Public Health Agency of Canada , who supported the development of the guideline, and to the  Knowledge Translation Program of St. Michael's Hospital  for their valuable contributions to patient engagement and knowledge translation work related to this guideline. The authors would like to thank  CADTH  for its systematic review on HCV screening, which supported this guideline, as well as the authors of the systematic review on HCV treatment ( Francesca Reyes Domingo ,  Nathalie M. Holmes ,  Rana Rahal ,  Mitulika Chawla ,  Kristin Klein  and  Alejandra Jaramillo Garcia ). The authors would like to thank  Dr William W. L. Wong  ( School of Pharmacy, University of Waterloo ) and  Dr Naveed Zafar Janjua  ( British Columbia Centre for Disease Control, School of Population and Public Health, University of British Columbia ) for their involvement as clinical experts and peer reviewers.
In order to increase the statistical power of our analyses, we also included individuals with ASD and controls from the Autism Brain Imaging Data Exchange (ABIDE I and II) samples. All details on inclusion criteria are available on the ABIDE Website (http://fcon_1000. projects. nitrc. org/indi/abide/) and have been published elsewhere  34, 35. We selected indviduals with ASD and controls with a minimum full scale IQ of 70. We excluded subects with an age below 18. We only included individuals with ASD for whom the entire volume of the cerebellum was available, resulting in the exclusion of 37 subjects (19 individuals with ASD and 18 controls). For ABIDE samples, in order to limit the site effect, we selected 5 sites that included more than ten individuals with ASD and ten controls matching our inclusion criteria (adults for whom the entire volume of the cerebellum was available).
MRI acquisition. All subjects recruited in France underwent an MRI acquisition on a 3T Siemens Magneton Tim Trio, with a standard twelve channels head coil, at the Neurospin neuroimaging center (CEA Saclay, 91, France). We used a 3DT1 MPRAGE sequence (160 slices, TR = 2200 ms, TE = 5. 16 ms, FOV = 256 × 256 mm 2 , voxels of 1 × 1 × 1. 1 mm). Acquisition parameters from the ABIDE dataset are described elsewhere (http:// fcon_1000. projects. nitrc. org/indi/abide/).
Cerebellum global segmentation and lobular parcellation pipeline. A flow chart describing the analyzed samples is reported in Fig. 1. First, we used FreeSurfer 5. 3. 0 software to perform global segmentation of cerebellar left and right cortical and white matter volumes. The automated procedure for volumetric measures of subcortical structures and cerebellum has been previously described  36, 37. This technique, performing segmentation and labeling of brain structures, is reported to be as effective as manual tracing  36. Second, to better understand the cerebellar structures in individuals with ASD, we performed a lobular parcellation of the cerebellum. We used two different methods (MAGeT Brain  38  for the anterior lobe and SUIT  39  for the vermis and Crus I) to perform cerebellar parcellation.
We performed parcellation of the anterior cerebellum using the MAGeT Brain pipeline because this method is more accurate in this particular region compared to the SUIT algorithm. Park et al. 38  compared both methods with manual segmentation, using high resolution MRI, in the anterior lobe of the cerebellum and found significant increased Kappa values in the anterior lobe (lobules I to IV and lobule V) with  Prior to the cerebellar parcellation with the MAGeT brain pipeline, we preprocessed (https://github. com/ CobraLab/minc-bpipe-library) the T1 images and performed N4 correction, cutneck and registration to the MNI space using the Advanced Normalization Tools (ANTs) software  40. The MAGeT brain  41  pipeline uses five high definition templates manually labeled by two expert raters. These templates are first tuned to the specificities of our acquisitions from the generation of multiple anatomical segmentations of representative images selected within our sample.
We excluded subjects with motion artifacts, with no full coverage of the cerebellum, with a significant segmentation defect in the cerebellum (either tissues mislabelled as cerebellum or cerebellar tissue not labeled as cerebellum) or with a significant anatomical abnormality in the posterior fossa (such as a cyst). We ensure that this quality check was efficient by visually inspecting the 3D volumes of 30 subjects as previously described  37. We excluded eight subjects because of a defect (non cerebellar volume segmented) in the cerebellar segmentation using the FreeSurfer software (five individuals with ASD and three controls), two controls due to a cyst in the posterior fossa and one subject due to significant motion artifacts. We thus performed FreeSurfer segmentation on a total of 134 individuals with ASD and 160 controls (Table  1 ).
Eye-tracking acquisitions and data processing. Subjects recruited in France underwent a free-viewing eye-tracking task using a screen-based (23", resolution set at 1920 × 1080 pixels) Tobii TX300 device (Tobii Technology, Stockholm, Sweden), allowing gaze acquisition at 300 Hz. After a five-point calibration, 18 dynamic avatar faces (Fig. 3 ) were presented, each remaining for three seconds and followed by a constant interstimulus interval (20 s). The faces randomly expressed dynamically fear, anger or happiness. We extracted the fixation time (in milliseconds) on eye regions for each of the three emotions. Our variable of interest was the average of this fixation time of the three conditions. Further details on the eye-tracking procedure are provided in Supplementary Material 3. See Fig. 1  (flow-chart) for the representation of subjects enrolled in both MRI and eye-tracking analyses.
To test the effect of IQ on our results in the ASD group, we conducted a linear regression considering (i) the ratio between cerebellar sub-volume and the global cerebellar volume as the dependent variable, (ii) sex as a cofactor and (iii) age and IQ as covariates. In our model testing the effect of fixation time to the eyes on cerebellar volume, we included IQ as a covariate in order to study the potential confounding effect of IQ. We included intra cranial volume (ICV) as a covariate in our parcellation analyses to account for the effect of ICV. We conducted all statistical analyses with SPSS version 20. 0 (IBM) at the exception of the FDR correction performed with python statsmodels open source library  43. 1. There were no significant differences in mean age or sex ratio between individuals with ASD and controls.
To our knowledge, no study has specifically examined differences in cerebellar volume in adult individuals with ASD. Several strengths support our study. First, we manually inspected each cerebellar segmentation. In the cerebellar parcellation analyses, we visually examined each slice of the cerebellum to ensure the quality of the segmentation. This quality control is key to reducing the inter-subject variability of the cerebellar shapes  68. While this information was not available for the individuals with ASD of the ABIDE database, all individuals with ASD recruited in France had no history of alcohol abuse or dependence which is well known to affect the cerebellum  69  and can lead to its size reduction  70, 71. Further, we only included adult individuals with ASD in our study to reduce clinical heterogeneity, which is a major limition to clinical studies and in particular neuroimaging studies  72.
Fountain et al. 73  highlighted six different developmental trajectories in children with ASD. Helles et al. 74  reported that 20% of adult men with a childhood diagnosis of Asperger syndrome no longer met criteria for a clinical ASD diagnosis and showed major improvements in general functioning. Clinical studies in children with ASD are likely to include heterogeneous individuals with ASD with potentially variable outcome in adult age. Studying adult individuals with ASD is important and interesting because this population is likely to have a stable diagnosis across the lifespan  75. Several limitations should be considered before interpreting our results. We were only able to examine the sub-volumes of the cerebellum for subjects recruited in France because of the heterogeneous quality of the MRI included from the ABIDE database and because only a subset of 59 subjects underwent an eye-tracking assessment.
4 dataset  [78] ) and topographic (ASTER Global Digital Elevation Model, http://reverb. echo. nasa. gov/) conditions (Figs  2  and 3 , Table  2 ). The altitudinal range of sampled populations was larger in Africa (365-1225 m) than in the Neotropics (25-72m). There was also a marked variation in dispersal vectors between continents (Table  1 ). In Paracou, samples included swamp and terra firme morphotypes. For this population, samples were collected for plastid DNA analysis, whereas SSR data (for different trees) was reanalysed from Degen et al. 2004  [72].
[30]. SSR data for Paracou was taken from Degen et al. [72]  and contained three loci. All SSR data were resolved on capillary sequencers (Applied Biosystems, Carlsbad, USA; see S1 File for experiment details and genotype matrices). The SSR loci of all populations belonged to a total set of six loci (Sg03 and Sg18  [72] ; SgC4 and Sg19  [59] ; Sg06 and Sg10  [79] ), but were not exactly the same in each population because of variable amplification and genotyping success due to large genetic distances among some of the populations  [38, 80]. Sequences of the psbA-trnH plastid DNA (cpDNA) intergenic spacer were generated for random subsamples from Paracou, Itubera, São Tome, Nkong Mekak and Mbikiliki, completing the data sets of Dick and Heuertz  [38]  and Budde et al. [30]  (see sample sizes in Table  2 ).
Data analysis Genetic diversity. The rarefied allelic richness (A R ) and the expected heterozygosity corrected for sample size (H E ) were computed for nuclear SSRs using SPAGeDi 1. 4c  [82] ; the standard error of H E was estimated from jackknife replicates using the PopGenKit package  [83]  in R version 3. 1. 1 [84]. To assess deviations from Hardy-Weinberg genotypic proportions, e. g. caused by non-random mating or null alleles, we computed the fixation index (F IS ) and tested deviation from zero using 10,000 permutations of alleles within populations in SPAGeDi. We estimated the frequencies of possible null alleles using the Brookfield2 estimator  [85, 86]  and estimated a fixation index corrected for null alleles in MicroChecker 2. 2. 3  [87]. Occasionally, multilocus genotypes were found more than once within populations.
The strength of FSGS was estimated as Sp = -b/(1-F ij(  1 ) )  [1]  where F ij(1) is the average kinship coefficient of individuals in the first distance class. The number and size of distance classes was defined for each population according to recommendations from the SPAGeDi user manual  [90] : similar numbers of pairwise comparisons across classes, > 50% of individuals present in each class and a coefficient of variation < 1 of the number of times each individual was represented in each class. As an alternative to Sp, we also performed a spatial principal component analysis (sPCA) in the adegenet package in R  [91]. This allowed us to test for overall FSGS (e. g. patches of related individuals, allele frequency gradients) using a G-test, and to estimate the strength of spatial structure as the eigenvalue of the first sPCA axis, eig.
To detect shared GPs among populations, STRUCTURE was run separately for the groups of populations that were genotyped together (to avoid mixing SSRs datasets for which allele identities were not cross-standardised: Itubera ánd African populations; Yasunı ´and BCI). Then the analysis was run within each population. We used an admixture model with correlated allele frequencies for codominant markers and 10 repetitions for each number of clusters, K, from 1 to 7, using a burn-in length of 20,000 and a run length of 80,000 iterations. Chain convergence was checked visually. The K that best described the data was determined as the one with the highest logarithm probability of data, ln Pr(X|K) (also referred to as L(K)), following Pritchard et al. [93] , and using the Delta K (ΔK) method described by Evanno et al.
We performed one-way ANOVA in R to detect if groups of individuals carrying the same haplotype differed in their mean individual sPCA scores. We also tested for association of haplotypes and GPs (Q!50%) using Fisher tests that ignored spatial autocorrelation in the data and we performed partial Mantel tests based on similarity matrices ("1" for pairs of individuals sharing the same haplotype or GP, "0" for pairs with different haplotypes or GPs) in which we controlled for spatial autocorrelation through a spatial distance matrix using the Ecodist package  [98]  in R. In Paracou, we further tested the association between GPs or haplotypes and morphotypes, similarly using Fisher and partial Mantel tests. Third, we examined altitudinal stratification of genetic variation in each population as would be expected, for example, in the case of restricted mobility of dispersers due to slopes  [99, 100].
Significant inbreeding was detected in all populations but Yasunı ´(Table  3 ). Microchecker detected null alleles in all inbred populations, but F IS corrected for null alleles remained significant in several populations, especially in Africa, suggesting non-random mating (Table  3 ). Twenty-five plastid DNA haplotypes were detected across populations. The psbA-trnH alignment varied at 28 positions, for sequence lengths of 289-515 bp. Polymorphism varied strongly between populations, from one haplotype in Yasunı ´to 6 and 7 haplotypes in the Cameroonian populations (Table  3 , see S3 File for the complete list of Genbank accession numbers, including the newly generated sequences KX572421-KX572686), a result that was mirrored in the estimates of rarefied haplotype richness (Table  3 ).
Although the number of SSRs used in our study was low (3-5), these highly polymorphic markers were able to detect significant FSGS in all and in six out of seven populations, by means of the G-test and Sp, respectively. This indicates a sufficient power for the purpose of the study. In fact, a dataset of 18 genic SSRs on ca. 30 individuals  [80]  had a lower power than our FSGS analyses (FSGS analyses on data from Olsson et al. 2016 are reported in S4 File). Another risk of using a low marker number is that it can lead to erroneous GP inference (e. g. using STRUCTURE) because few markers do not capture well the diversity of stochastic lineage sorting processes due to random genetic drift  [103]. To mitigate this potential problem, we used two types of cyto-nuclear and habitat association analyses, i.
Acknowledgments We thank  Tariq Ste  ´vart ( Missouri Botanical Garden ),  Gilles Dauby  and  Olivier Hardy  ( UniversiteLibre de Bruxelles ),  Peter Mambo ,  Green Connexion Cameroon, IRD Cameroon, and EcoFoG  staff for help with sampling,  Carmen Garcı ´a-Barriga  and  Zaida Lorenzo  ( INIA-CIFOR ) for assistance in the laboratory,  Jesus Martı ´nez Fernandez  for his help with map handling, and  Gregor Unger  and  Mario Zabal Aguirre  for assistance in data editing.
This work was supported by the  Ministerio de Ciencia e Innovacion (ES) , http:// www. idi. mineco. gob. es/portal/site/MICINN/,grant  CGL2012-40129-C02-02 , to MH;  Ministerio de Ciencia e Innovacion (ES) , PhD scholarship FPI  BES-2009-015443  to KBB;  Ministerio de Ciencia e Innovacion (ES) , ' Ramon y Cajal ' fellowship  RYC2009-04537  to MH;  Ministerio de Educacion ,  Cultura y Deporte , http://www. mecd. gob. es/portada-mecd/, PhD scholarship  FPU 12/00125  to PTB; European Commission  FP7 People: Marie Curie Actions , http://ec. europa. eu/programmes/horizon2020/,  Marie-Curie Intra-European fellowship   PIEF-GA-2012-329088  to MH;  Research Council of Norway , http://www. forskningsradet. no/, grant  203822/E40  to MH;  German National Academic Foundation , http://www. studienstiftung.
de/, PhD scholarship to KH;  Agence Nationale de la Recherche  (FR), http://www. agence-nationalerecherche. fr/," Investissement d'Avenir " grant CEBA, ref. ANR-10-LABX-0025 , to CSS and MH and the  European Social Fund , http://ec. europa. eu/esf/home. jsp,PhD grant to MC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Results: The parasite fragment sequences of cob fragments from AE patients showed two haplotypes, and nad2 gene fragment sequences had four haplotypes. The gene sequences from Microtus sp. were 100% identical to the sequences of some isolates from AE patients. These haplotypes were distributed in both Qinghai and Xinjiang provinces. Alignment analysis with the sequences from the GenBank databases showed five genotypes including three Asian genotypes, one from Europe and one from North America. Conclusions: Most AE patients harbored the Asian genotype 1 which may be an indication of its relative frequency in the definitive hosts and the environment or of its pathogenicity to humans, which calls for further research.
Large genetic variations within the parasite species might be expected from such range and diversity as a response to various hosts and environmental adaptation. Paradoxically, little genetic variation was detected within E. multilocularis which was initially classified into two genotypes only, M1 (Europe) and M2 (China, Alaska and North America) based on four nucleotide substitutions out of 471 nt of mitochondrial NADH dehydrogenase subunit 1 gene  [12]. However, based on sequence data of mitochondrial and nuclear DNA, further geographical distinctions were found with European, Asian and North American clades, and one unrelated haplotype from Inner Mongolia  [13]. In fact, there are very few mitochondrial sequences of E. multilocularis from AE patients deposited in the GenBank database. In the present study, we sequenced two mitochondrial (mt) genes (fragments) from parasitic liver tissues of 56 human AE cases and six isolates of E.
DNA sequence alignment and analysis To sequence the gene fragments, we isolated PCR products from agarose gel (0. 8%, w/v) by using the QIAquick Gel Extraction Kit (Qiagen, Hilden, Germany), and then inserted the DNA into an AT vector (pMD19-T Vector, TAKARA BIO INC, Shiga,. Japan)), according to these manufacture's instructions. Clones containing inserts were sent to sequencing company for sequencing. The sequences obtained were aligned using Bioedit version 5 (http://www. mbio. ncsu. edu/bioedit/bioedit. html/) and compared to the reference sequences from the GenBank database. Phylogenetic analysis was performed using MEGA 6  [14]  and phylogenetic trees were constructed using neighbor-joining (NJ) method [Kimura's two-parameter distance analysis with a gamma shape parameter (a = 0. 5)].
Sequence variation among the isolates maintained in laboratory The size of the amplified DNA fragments obtained from E. multilocularis isolates was 526 bp and 474 bp for cob and nad2, respectively (GenBank accession numbers: KT965443-KT965494; KY290762-KY290791). Figure  1  shows the substitution nucleotides of the two gene fragments amplified from the three isolates maintained in our laboratory and the three isolates we recently collected from wild rodents in Yili, Xinjiang. The comparison with the different haplotypes of the sequences deposited in the GenBank database showed that E. multilocularis is variable at the genomic level. It showed that nad2 sequences isolated from China were variable with a single base substitution compared with the sequences from France, Japan and Slovakia, two or more nucleotide substitutions from those from Canada and USA (Alaska).
One of the cob haplotypes from China was identical to the sequences isolated from France and Slovakia, whereas, there are 5 substitutions compared with the sequences from Alaska, USA. The haplotype Em-A is identical to the sequence of the isolate collected from the St. Lawrence Island in Alaska (GenBank: AB461409), which is different from the two laboratory maintained isolates collected from China. The genetic divergence of cob and nad2 gene fragments between Em-NX/Em-XJ and Em-A ranged from 0. 85 to 0. 95%.
Sequence analysis of E. multilocularis isolated from patients infected with alveolar echinococcosis (AE) Liver tissue samples were collected from 56 AE patients by surgical removal. In total, 68 sequences were obtained from these samples including 32 nad2 gene sequences (including 24 from Xinjiang, 4 from Qinghai, 3 from Sichuan and 1 from Gansu); 36 cob gene sequences (23 from Xinjiang, 10 from Qinghai, one from Sichuan, Gansu and Beijing, respectively). There are few E. multilocularis sequences from AE patients deposited in the DNA sequence databases, which may indicate the difficulty to obtain material or to amplify DNA fragments from surgical samples from AE patients. We extracted parasite DNA from three  different sources of tissues. From the frozen tissues, 21 cob and 21 nad2 sequences were obtained from the 24 samples available (success rate: 87.