dataesr/scientific-paragraphs-categorization huggingface dataset:
Demographic (age, gender, ethnicity) and geographic (home village) characteristics of patients were recorded. The epidemiological data were used to create two separate datasets: One aggregated at the village level (one row per location) and another was maintained at the individual level, with one row per individual. The official Lao PDR censuses from 2005 and 2015 were used to geocode villages (based on village name and administrative units listed in patient records) and to assign village population estimates to each village (taking a mean population size between 2005 and 2015). Village location and population sizes were then merged to both the individualand village-level datasets. A subset of villages within the geographic region of the home villages of included patients was selected by overlaying a standard deviational ellipse with 3 standard deviations (calculations described in S2 Text) around the patient home villages and then selecting all villages within that ellipse (S2 Fig).
These villages were then retained for village level comparisons between villages populated, and not populated, with patients admitted with CNS disease needing an LP. This subset was chosen to ensure that the analysis was limited to the region from which the cases for this project came, thereby using villages that share similar geographic attributes for comparison. Using all villages within the nation would have meant the inclusion of parts of Lao PDR (especially in the far south) that have very different environmental patterns. This subset of villages is hereafter referred to as the "study area". Major road network data was taken from OpenStreetMaps (http://www. openstreetmap. la), selecting "primary", "secondary", and all major connecting roads (downloaded in February 2017, S3 Fig). Primary and secondary roads are the two largest road classifications for the nation.
Primary roads link major towns and cities and secondary roads link mid-sized towns. Primary and secondary link roads are ramps or slip roads that connect other roads to primary or secondary roads. Together, these types of roads are hereafter referred to as "major roads". Smaller roads were not included in this analysis as they are less likely to be accurately included in the OpenStreetMaps data. The Euclidian distance was then calculated from all villages in the census to the nearest point along a major road. These distances were merged to both the village-and the individual-level datasets. Environmental predictor variables for vegetation and surface water were derived from Moderate Resolution Imaging Spectroradiometer (MODIS) products (MOD13Q1/MYD13Q1 250 meter AQUA/TERRA 16 day composites).
Since many infectious diseases, especially vector borne diseases, are strongly influenced by environmental factors we hypothesized that indicators of vegetation and surface flooding would correlate with some specific diagnoses. Three environmental indices were downloaded and considered in these analyses: a normalized flooding index (NFI)  [18] ; the normalized difference vegetative index (NDVI); and the enhanced vegetation index (EVI). NFI is indicative of surface water, NDVI is indicative of green surface vegetation, and EVI is an improved measure of green vegetation that is intended to account for dense forest canopies and atmospheric conditions that can lead to error in NDVI measurements. Data were downloaded for each of these environmental indices (EI) within each 16-day time period from February 2002 through December of 2011.
The final analyses conducted in this research retained only the EVI and NFI for environmental predictors (summary statistics for NDVI are included) because NDVI and EVI were strongly correlated. The EIs are described in more detail in S3 Text. The environmental raster data were then summarized and extracted based on varying buffer sizes (2km, 5km, and 10km) for each village in the individual-and village-level datasets. Permanent water bodies (such as the Mekong River and Nam Ngum Dam) were masked from the NFI calculations. For the village-level datasets, mean values of each environmental variable was calculated for the study period duration and used as an indicator of "average" vegetation or surface water characteristics of each village. For the individual-level dataset the values were extracted based on the admission date, using increasing durations of time prior to admission (within the same month, within the previous 2 months, within the previous year).
e. MODIS) and software (R and QGIS) and routinely collected healthcare data. Surveillance systems and potentially diagnostic algorithms  [38]  in developing settings could benefit from inclusion of such resources. More comprehensive studies that investigate these important causative agents of CNS infections would provide a better understanding of the environmental drivers of these diseases. A far-reaching surveillance system that is representative of the entire nation and includes likely CNS infections would be beneficial in order to assess the true burden of CNS infections-many of which would benefit from primary and secondary prevention through increased provision of vaccines, vector control, and early diagnosis and treatment. Given the inherent difficulties in accurately diagnosing and treating CNS infections, the predictors reported here and from other epidemiological studies for major contributors to CNS diseases (i.
Acknowledgments We are very grateful to the patients and to  Bounthaphany Bounxouei , past Director of  Mahosot Hospital ; to  Bounnack Saysanasongkham , Director of  Department of Health Care, Ministry of Health ; to  H. E. Bounkong Syhavong , Minister of Health, Lao PDR; to the staff of the  Infectious Disease Center and Microbiology Laboratory  for their help and support.
This study was supported by the  European Commission Innovate program  ( ComAcross  project, grant no. DCI-ASIE/2013/315-047 ). The work of LOMWRU, PN and MM are funded by the  Wellcome Trust of Great Britain , grant  106698/Z/14/Z. Travel to  Lao PDR  to support  DMP  for this research was obtained through a  University of California Council on Research, Computing , and  Libraries (CORCL)   Faculty Grant. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Software All maps were created using QGIS version 3. 4. 9. R cran version 3. 5. 2 was used for downloading, processing, and wrangling MODIS data (using the "MODIStsp"; "raster"; "rgdal"; and "maptools" packages) and for all regressions. The "mgcv" package was used for GAMs and the lme4 package was used for the generalized mixed models. Euclidian distances between villages and major roads were calculated using QGIS. ArcMap version 10. 5. 1 was used to calculate SDDs and SDEs.
MBP-TET1 fragments purified using an amylose resin were examined for co-purifying NANOG by immunoblotting. NANOG co-purified with all TET1 fragments, except TET1(1-108) which showed a dramatically decreased interaction with NANOG (Figure  1(d) ). Importantly, these experiments confirmed a direct physical interaction and narrowed down the first NANOG-interacting domain (NID 1) to 11 residues (109-120). Protein alignments showed that NID 1 is highly conserved among mammals, indicating a selective pressure for the conservation of these TET1 residues (Figure  S1 (e)). However, residues 109-120 of TET1 do not align with TET2 or TET3 proteins (data not shown). To identify which residues are responsible for binding to NANOG, the MBP-TET1 1-120 plasmid construct was modified by alanine substitution of specific amino acids (proline, glutamine, arginine, leucine, serine and valine) within residues 109-120 (Figure  1 (e)).
The binding of NANOG to each mutant construct was assessed following bacterial expression and TET1 purification. Strikingly, only the L?A mutant (L110A, L114A) showed a decreased interaction with NANOG, which was reduced to a similar extent as the negative control TET1 1-108 (Figure  1(f) ). Together, these data indicate that one or both of the two evolutionary conserved leucine residues (L110 and/or L114) are in direct physical interaction with NANOG. To determine which regions of NANOG interact directly with the TET1 N-terminus, MBP-TET1 1-321 was co-expressed with several (His) 6 -tagged NANOG truncations in E. coli (Figure  2(a) ). Surprisingly, the TET1 N-terminus interacted with three out of four NANOG truncations: 1-160, 91-246, and 194-305 (Figure  2(b) ). However, the TET1 N-terminus showed no interaction with the NANOG homeodomain (Figure  2(b) ).
To identify genomic sites potentially regulated by the TET1-NANOG complex, published TET1 and NANOG ChIP-seq datasets were compared. TET1 ChIP-seq peaks from two independent datasets  23, 24  showed an overlap of 13,279 "high confidence" TET1 binding sites (Figure  S6(a) ). A similar analysis of two NANOG ChIP-seq studies  38, 39  identified 24,357 "high confidence" NANOG ChIP-seq peaks (Figure  S6(b) ). Subsequently, TET1 and NANOG ChIP-seq signals were visualised at high confidence NANOG and TET1 binding sites, respectively. Interestingly, TET1 is enriched at the centre of a large proportion of NANOG binding sites in ESCs, and this signal is abolished upon Tet1 knockdown (Figure  7(a) ). In contrast, NANOG is enriched only at a small proportion of TET1 binding sites in ESCs (Figure  S6(c) ).
Here, comparative analysis of TET1 and NANOG ChIP-seq datasets identified a subset of genomic loci co-bound by TET1 and NANOG in ESCs that mainly correspond to pluripotency enhancers. In contrast to most TET1 binding sites that show a broad TET1 ChIP signal, TET1 binding at TET1-NANOG co-bound sites is more narrowly focussed on NANOG peaks. Further supporting NANOG-mediated targeting to these loci, de novo motif analysis of these sites identified the SOX2/ OCT4 motif, which characterises NANOG ChIPseq peaks in ESCs. 61 About half of NANOG target genes have a TET1-NANOG peak nearby, suggesting that TET1 may act cooperatively with NANOG to regulate transcription. 62 NANOG target genes that have an associated TET1-NANOG peak include genes that are either activated or repressed by NANOG in ESCs.
LC5925; or Chameleon Duo Pre-stained ladder LI-COR, cat. 928-60000). For protein quantification, the relevant bands were quantified using the LI-COR Image Studio Software. To identify evolutionary conserved residues, TET1 protein sequences from various mammalian and non-mammalian species were downloaded from UNIPROT (https://www. uniprot. org/) and aligned using ESPript (http://espript. ibcp. fr). 67 hIP-seq analysis ChIP-seq datasets were analysed using the Galaxy platform (https://usegalaxy. org). 68  Details concerning the bioinformatic workflow are available at the following address: https://usegalaxy. org/u/ raf4579/w/workflow-chip-seq-1. Raw sequencing data (FASTQ files) was downloaded from publicly available databases NCBI's Gene Expression Omnibus or ArrayExpress. Quality control was performed using the software "FastQC" (Babraham Bioinformatics).
Sa ples were filtered to remove contaminating adapter sequences and low-quality reads (cut-off quality score >20. 0). Reads were mapped to the mouse mm9 reference genome using "Bowtie2" (BAM file output). 69  Reads were mapped only to a unique genomic location (k = 1). ChIP-seq peaks were called using the software "MACS2" (BED file output). 70  The immunoprecipitated sample was compared to the genomic input for identifying statistically significant binding sites (qvalue 0. 05). For the analysis of NANOG ChIP-seq datasets, the algorithm optimised for "narrow peaks" was used. For the analysis of TET1 ChIP-seq datasets, the algorithm optimised for "broad peaks" was used. If replicates were available, only ChIP-seq peaks shared between replicates were considered for further analyses. Peaks were considered as shared between datasets when presenting an overlap of at least 1 bp.
To visualise ChIP-seq datasets on a genome browser, mapped reads (BAM files) from TET1 ChIP-seq with (GSM611195) or without (GSM611194) Tet1 knockdown, as well as NANOG ChIP-seq (GSM1082342) were converted into big-Wig files using "Deeptools". 71  Data was normalised in "Reads Per Kilobase Million" (RPKM) to allow the comparison between ChIP-seq datasets. Genomic snapshots were taken using the genome viewer "IGV". 72  To visualise ChIP-seq datasets as heatmaps, the software "Deeptools" was used. 71  To perform de novo motif analysis on ChIP-seq datasets, the DNA sequences corresponding to each ChIPseq peak were extracted (FASTA file output) and analysed using the "MEME" software. 73  Motifs between 5 and 25 bp, enriched with a E value <0. 05, were identified. These results were compared to known protein motifs in the JASPAR database.
Background: Although it is known that Zika virus (ZIKV) infection during pregnancy may lead to microcephaly in the fetus, the prognostic factors associated with this tragic disorder remain unclear. We conducted a systematic review and meta-analysis to assess the prognostic factors associated with the incidence of microcephaly in congenital ZIKV infection. Methods: We conducted a comprehensive search in Ovid MEDLINE, Ovid MEDLINE (R) Epub ahead of print, Embase, Embase Classic, Web of Science, CINAHL, Cochrane CENTRAL, LILACS, and various thesis databases to identify human studies reporting microcephaly associated with congenital ZIKV infection. We requested primary data from the authors of the included studies to calculate summary estimates and conduct the meta-analysis of the most prevalent factors.
Information sources and search strategies The search strategy aimed to find pertinent data in theses and dissertations in addition to published studies. The following databases were searched by a university librarian on January 8, 2019: MEDLINE via OvidSP (1946 onward), Embase via OvidSP (1947 onward), Cochrane Central Register of Controlled Trials or "Cochrane CENTRAL" via OvidSP (1991 onward), the Cumulative Index of Nursing and Allied Health Literature or "CINAHL" via EBSCOhost (1981 onward), Web of Science Core Collection (1900 onward), ProQuest Dissertations and Theses Global (1861 onward), and Latin American & Caribbean Health Sciences Literature or "LILACS" (1982 onward). The full electronic search strategies for all databases can be accessed via QSpace, Queen's University's research repository service [http:// hdl.
handle. net/1974/24246]. No language or date restrictions were applied. The reference list of systematic reviews and reports were searched for additional studies. We searched ProQuest Dissertations and Theses and thesis databases from Brazil, Colombia, Canada, USA, and Europe on January 8, 2019, using the terms "zika" or "zikv" or "zyca" or "zyka". The authors of editorials, correspondence, and conference abstracts that met the inclusion criteria were searched online for original papers. Additionally, we identified studies that we believed concern PZIK, the prognostic factors of interest, and.
Eligibility We included published data from original research that studied microcephaly as a congenital effect of ZIKV in humans. We included randomized controlled trials, prospective, retrospective or descriptive cohorts, case series (only the case series whose primary data allowed the formation of groups that were prospectively compared regarding outcome), and cross-sectional and case-control studies that could answer the review question. Studies were excluded if they: (1) were not in humans; (2) did not report our primary objectives; (3) were in vitro/cell studies; (4) were not original research, such as literature reviews, guidelines and manuals, protocol summaries, editorials, opinion pieces, or book chapters; (5) duplicated publications from the same sources (data from the same sources, but published in different papers); or (6) were case reports, epidemiological analyses/ bulletins, or case series that included outcomes for only one group.
Study selection, data extraction, and assessment of studies Initial triage of articles was based on the screening of titles and abstracts by two independent evaluators to assess the relevance to the objective of the review. Then, a full-text read of the selected studies was conducted to determine inclusion according to eligibility criteria and the study question. Data extraction and quality assessment were conducted by two independent authors using a standardized instrument. Disagreements at any stage were resolved by consensus or discussion with a third author. Data extracted included the name of first author, year of publication, period of study, country, language, study design, size, population, and any potential patientrelated prognostic factors. These included demography (maternal age, ethnicity, deprivation, education level, marital status, social support); lifestyle factors (smoking habits, drug use); patient history (including comorbidity, family history); symptom type; health care usage (including screening); presenting behaviour; symptom knowledge; and characterization of outcomes.
The random effects model was used when the I 2 test demonstrated a large degree of heterogeneity between studies (I 2 higher than 0. 5). When the heterogeneity between studies was equal or lower than 0. 5, fixed-effect model was used for the analysis. We used the RevMan software to execute the calculation of summary measures and heterogeneity of the studies, and to generate the figures of the meta-analysis (Forest plots).
Studies that provided data to conduct the meta-analysis Six studies provided primary data to perform the metaanalysis  [27, 30, 32, [35] [36] [37]. Three of them  [32, 35, 36]  had prospective designs, two  [27, 30]  had retrospective designs, and one  [37]  was a cross-sectional study. The study by Ventura et al. [37]  was the only cross-sectional one, and therefore, we were not able to incorporate the data into the meta-analysis. For this reason, we describe it briefly, below. Ventura et al. [37]  provided data on 148 cases of PZIK. Microcephaly status (presence or absence) was reported for 140 (94. 6%) of these infants. Of these, 124 (88. 6%) presented microcephaly. In the microcephaly group, 56. 45% (n = 70) were female, while in the nonmicrocephaly group, the majority were male (n = 9/16, 56,25%).
42; 95% CI 1. 09, 1. 84, I 2 = 0%) for microcephaly, compared to infection in the second and third trimesters of pregnancy. A decrease in the microcephaly detection risk rate was observed in women who did not presented symptoms of PZIK (RR 0. 68; 95% CI 0. 60, 0. 77; I 2 = 38%), such as conjunctivitis, pruritus, and rash (Fig. 2c ). There was no statistically significant difference between groups regarding maternal ethnicitywhite (RR 0. 91; 95% CI 0. 77, 1. 08; I 2 = 0%)or the absence of tobacco, alcohol, and/or other substance consumption (RR 0. 84, 95% CI 0. 55, 1. 29, I 2 = 0%), although the point estimates indicated these characteristics as probable protective factors. Maternal age and gestational age at birthanalysed using mean and SDwere also similar between groups. The meta-analysis data of the factors that did not significantly increase the risk are illustrated in the Additional Fig.
Limitations of this systematic review Common sources of bias in any meta-analysis are publication bias and heterogeneity between studies. We assessed the publication bias by reviewing the grey literature, looking for recent published manuscripts by authors who published theses and presented conference abstracts, and contacting them. Despite this effort, no additional data were found. Thus, the meta-analysis only included published studies. Because of the small number of included studies, we were not able to perform tests to detect publication bias. Since nonsignificant results have a decreased likelihood of publication, we believe that the included studies might be reporting a higher association between PZIK and birth defects than may generally be the case. However, in terms of associated prognostic factors for the development of microcephalyour exposures of interest -, it is unlikely that publication bias would affect our results.
Regarding summary measures, we understand that our data also reflect the number of participants in each study (and not the methodological quality of them), as is observed in all unweighted summary measures. Concerning the design of the studies, the case-series studies did actually include the entire available populations, using surveillance strategies, tending to have the characteristics of a descriptive cohort study. However, due to the small number of participants, they were designed and assessed as case-series. Moreover, the small number of individuals included in the retrospective studies restricted the power of the meta-analysis. Specific limitations of our review were the noninclusion of in vitro studies in the eligibility criteriasome authors have reported that the ZIKV strain can be related to varied outcomes  [71, 72]  -, and the inherent differences between studies, especially in regard to the ZIKV infection definition and data collection.
Acknowledgements We acknowledge all the co-authors of the primary studies included in the meta-analysis. Additionally, we thank all the involved staff at the  Centre Pluridisciplinaire de Diagnostic Prénatal de la Martinique  and the  French National Agency for Public Health  for its participation in the  French West Indies Registry of Congenital Anomalies ;  Camilla Rocha  for her analysis of the Altino Ventura Foundation data; and  Darcy Dunton  for the linguistic editing of the manuscript. This work was conducted during a visiting scholar period at  Queen's University, Canada , sponsored by the  Capes Foundation of the Ministry of Education, Brazil  (grant no. 88881. 133664/2016-01 ).
Results The variation between DUHi and FVB molar morphology follows the murine evolutionary lines of least resistance In order to place these two strains within the context of natural variation in molar tooth shape, we compared the outline of first molars in a number of murine groups, including Mus musculus domesticus from the wild and three lab strains (two inbred strains: FVB, DUHi; one outbred strain CD1). We performed a principal component analysis (PCA) of outline descriptors (obtained from an outline analysis of the 2D outline, see methods) as an agnostic method (i. e. it does not make strong assumptions about the shape of the underlying variation) to reveal the main direction of variation in the dataset, and a direct comparison of molar Length/Width ratio (Figure  1 ). For both the upper and lower molar, the first axis of the PCA contrasts broad with narrow outlines.
g. cap transition occurs at earlier c dpc in FVB). The detailed model and the script are provided in Appendix 1. An important stochastic term in the model corresponds to the part of the inter litter variation of the body weight due to pregnancy, for which we explored two values (Figures  of Appendix 1 ). The first one, which we consider realistic, corresponds to a maximum effect on weight of 20 mg for a 200 mg embryo. The second one, which we consider an extreme upper bound, corresponds to a maximum effect on weight twice as important (40 mg for a 200 mg embryo). The computed embryonic ages (next called c dpc, for computed days post coı ¨tum) presented in the main text have been estimated using the realistic parameter, but the results are qualitatively robust using the upper bound parameter (Appendix 1figures 2-8).