dataesr/scientific-paragraphs-categorization huggingface dataset:
Cluster analysis of quantified in situ hybridizations For all seven stages of development from blastula to late planula, in situs of suitable genes have been quantified. The expression profiles are provided in Additional file 1 in MATLAB format. The quantified patterns are ordered in dendrograms and correlation matrices. The number of analyzed patterns from each stage are: 112 from the blastula (Fig. 6 ); 52 from the early gastrula (Fig. 7 ); 18 from the Fig. 9  Hierarchical clustering of gene expression profiles in the late gastrula stage. The dendrogram is cut off at a similarity of 0. 6 mid gastrula (Fig. 8 ); 25 from the late gastrula (Fig. 9 ); 15 from the early planula (Fig. 10 ); 17 from the planula (Fig. 11 ) and 13 from the late planula (Fig. 12 ). From the correlation matrices, major and minor blocks are identified.
Overview and analysis of expression summaries From the Kahi Kai gene expression database, 73 genes have hybridization images available for at least two stages from blastula to late planula. These genes are listed with descriptions of their expression in a Microsoft Access database sheet (Additional file 2). Counts of pairwise expression domains are listed in a Microsoft Excel spreadsheet (Additional file 3). The central domain/endoderm, central ring/external ring/oral ectoderm and vegetal hemisphere/aboral ectoderm are selected as major expression regions. The changes or lack of change in expression patterns starting in a single major expression region are shown in A total of 25 genes for which in situs are available in the blastula stage are exclusively expressed in the central domain. From these genes, 22 are expressed in the endoderm in the next stage with available in situs.
During gastrulation, Bmp ligands and antagonists are asymmetrically expressed along the secondary axis  [13]. Based on these observations, determination of the secondary axis may coincide with the mid blastula transition. The asynchrony in cell divisions then produces a stochastic perturbation in a morphogen concentration which would define the secondary axis. The gene expression database contains various genes that are differentially expressed along the secondary axis, although most are not identified in the expression summaries. From the incomplete list of genes included in the expression pattern overview in this study (Additional file 2), various genes involved in secondary axis formation can already be identified. The genes Anthox7, Anthox8b, Bmp2/4, chordin, Gbx, Hex, Msx, Msx2, NvHD060, Smad1/5 and Vent1 exhibit noncylindrical expression patterns.
Quantification of these patterns requires a two-dimensional or three-dimensional template and eventually a three-dimensional detection method. Especially Vent1 asymmetric expression in the early gastrula stands out. In various animals, vent genes are involved in a Bmp signaling feedback loop  [20]. Curiously, the genes Bmp2/4, chordin and Smad1/5 in this signaling pathway are still symmetrically expressed in the N. vectensis early gastrula (or at least their asymmetry is less pronounced). The N. vectensis in situ hybridization collection contains expression data for less than half of all developmental stages for most genes stored. Despite the sparsity of this dataset, a large-scale analysis results in meaningful insights. Sparse data is common for databases that contain labor intensive measurements, and standardization allows global analysis approaches to be applied to incomplete biological databases.
Conclusions Our cluster analysis indicates that early gene expression domains in N. vectensis are spatially separated in a stable sequence along the primary body axis. An additional statistical analysis indicates that precise gene expression domains in N. vectensis are generally formed by two processes. Genes that are expressed in the blastula appear in broad expression regions. During gastrulation and planula development, the expression domains are refined within the boundaries of these broad regions. It should be stressed that no additional experiments have been performed for our study. Spatial expression data in a public gene expression database have been quantified and analysed, and these analyses resulted in new hypotheses on cellular migration in N. vectensis. Spatial gene expression patterns have been collected in extensive databases for other model animals as well, and a similar computational approach can generate hypotheses about cellular migration before fate maps are available for these animals.
Fluorescence Quantification of Actin Staining at TBCs Only images of intact apical processes containing stage VII spermatids with associated apical processes of Sertoli cells from fragmented tissue were used in the quantification analysis. The process used to get an index of the area occupied by the actin networks at TBC clusters was carried out using ImageJ software version 1. 48  [23]. All spermatids used for quantification were rotated to have the same orientation. For each experiment, controls were used to set the appropriate threshold value that would best represent only the staining of the actin networks at TBC clusters. This threshold was then applied to all spermatids analyzed in that specific experiment. The analyze particles function was used to count the number of pixels above the threshold in a region that was defined by an oval shape.
Stained sections were imaged using a Tecnai G2 Spirit electron microscope (FEI North America NanoPort) operated at 120 kV. Qualitative observations of the drug experiments were made while scanning sections on the microscope and on the basis of a total of 377 digital images. Electron micrographs presented in the figures are representative images. Quantitative data for the diameters of TBCs were made on an additional 153 images taken specifically for that purpose.
Quantification of TBC Proximal Tubule Diameters Two previously unsectioned blocks of embedded tissue were sectioned for each treatment and control testis for each experiment, and images collected for quantifying the diameters of the proximal tubular regions of TBCs. Images were taken of proximal tubules from different clusters of complexes in sections from each block (total of 12 blocks, 2 each for each of the control and experimental testes from the three animals; one animal for each dose). Each TBC was photographed at 68 0003 on the microscope. The diameters of tubular regions were measured using ImageJ software version 1. 48. A one-tailed, unpaired t-test with Welch correction was used to test for significant differences between the diameters of the tubular regions in experimental and control groups.
Acknowledgment. C. L. A. acknowledges the  Sims Scholarship  from the  University of Cambridge. J. L. M. D. acknowledges funding from the  European Research Council   Advanced Investigator Grant   NOVOX ERC-2009-adG247276ERC. M. L. B. thanks the  German National Academic Foundation (Studienstiftung)  and the  Engineering and Physical Sciences Research Council  Grant  RG53717 KJZA/098  for funding. C. L. A. thanks  A. Kursumovic  for help and useful discussions. The data underlying this publication are available at https://www. repository. cam. ac. uk/handle/ 1810/252459.
Background: Little is known regarding the recognition of anxiety in children and young people (CYP) in primary care. This study examined trends in the presentation, recognition and recording of anxiety and of anxiolytic and hypnotic prescriptions for CYP in primary care. Method: A population-based retrospective electronic cohort of individuals aged 6-18 years between 2003 and 2011 within the Secure Anonymised Information Linkage (SAIL) Databank primary care database was created. Incidence rates were calculated using person years at risk (PYAR) as a denominator accounting for deprivation, age and gender. Results: We identified a cohort of 311,343 registered individuals providing a total of 1,546,489 person years of follow up. The incidence of anxiety symptoms more than tripled over the study period (Incidence Rate Ratio (IRR) ¼3.
Ethical approval Approval was granted from the HIRU Information Governance Review Panel (IGRP), an independent body consisting of a range of government, regulatory and professional agencies, which overseas study approvals in line with permissions already granted to the analysis of data in the SAIL databank  (Lyons et al. , 2009; Ford et al. , 2009). We plan to follow the key points of the MRC/Wellcome Trust data sharing policy.
Data source The Secure Anonymised Data Linkage (SAIL) databank is an expanding data repository (over 2 billion records) of anonymised person based linkable data to support research. SAIL was established by the HIRU at Swansea University in 2004 and forms part of the Health e-Research Collaboration UK (HeRC UK), led by the Medical Research Council (MRC) and based in the Centre for the Improvement of Population Health through e-Records Research (CIPHER). CIPHER is a UK Clinical Research Collaboration (UKCRC) Public Health Research Centre of Excellence set within the Farr Institute at the College of Medicine at Swansea University. Policies, structures and controls are in place to protect patient confidentiality, along with a high performance computing infrastructure and a reliable matching, anonymisation and encryption process, which is achieved in conjunction the NHS Wales Informatics Service.
Data are imported into SAIL via a split file approach, whereby demographic and clinical data are separated at source later to be rejoined fully encrypted with an allocation of a unique identifier. This split file method ensures anonymisation and confidentiality, whilst maintaining the facility of data linkage at the level of the individual to any of the datasets housed in SAIL  (Lyons et al. , 2009; Ford et al. , 2009). This allows data from sources including general practice records, hospital admissions and demographic information to be linked at patient level whilst maintaining anonymity. In this study data were utilised from: NHS Administrative Register (NHS AR) a register of all individuals registered with a Welsh General Practitioner or who have ever had contact with the NHS; General Practice Database (GPD) attendance and clinical information for all general practice interactions including symptoms, investigations, diagnoses and prescribed medication.
Study population and setting Individuals aged from 6 to 18 years between 1st of January 2003 and 31st December 2011 were identified. Data collection began either six months from GP registration or at the study onset whichever was the later to exclude the risk of retrospective recording. Data collection ended at the end of registration with a SAIL supplying GP, date of death, 19th birthday or the study end whichever was the sooner. Individuals supplying a minimum of six months of data based on these criteria (and therefore registered with a SAIL supplying GP for a minimum of one year) were included in the cohort. Each individual could supply more than one period of data provided the above criterion were met. For each year, data were collected between the start and end dates identified when constructing the original cohort or, between the 1st of January and the 31st of December if an individual's period of data collection spanned beyond these dates.
Measures Demographic information (age, gender, lower super output area based deprivation quintile using the Welsh Index of Multiple Deprivation) were collected. Age and residential information for each individual was collected based upon the onset of data collection for each year. Age was described according to categories of 6-10, 11-14 and 15-18 years in accordance with other studies of this type  (Wijaars et al. , 2012)  except where numbers were small when 6-14 and 15-18 age ranges were used. Other measures were taken from GP computer records using primary care Read codes. The Read codes and algorithms being used to identify a new episode of symptoms/diagnoses of anxiety have been developed and utilised in previous research (Supplementary Table  1 )  (Walters et al. , 2012; John et al. , 2015).
Annual prevalence of each subtype was measured. An annual prevalent case was defined as an individual with any record of a given subtype in a target year  (Frisher et al. , 2004). Cohorts for each year were interrogated to identify individuals with new (incident) diagnosis/symptoms of anxiety, mixed anxiety and depression and panic disorder/panic attacks defined as no record of a given subtype in the previous 12 months. Participants may have more than one episode recorded for each subtype as long a period of at least 12 months exists between entries in keeping with previous studies of this type  (Rait et al. , 2009; Wijaars et al. , 2012; Walters et al. , 2012). Data were also collected on incident anxiolytic and hypnotic prescriptions by BNF (British Medical Association and Royal Pharmaceutical Society of Great Britain, 2014) categories (Sections 4.
1. 1 and 4. 1. 2) excluding barbiturates (Section 4. 1. 3) and antihistamines (Section 3. 4. 1) (Supplementary Table  2 ). Routine data does not explicitly link medication prescription with diagnosis. Individuals with an anxiolytic prescription were further analysed in an attempt to identify the indication for which the medication was prescribed. Routinely collected electronic GP data records were reviewed for 6 months either side of the initial prescription date for depression and anxiety diagnosis and symptoms before searching for other possible indications  (Gardarsdottir et al. , 2007). These were: pain, enuresis, attention deficit hyperactivity disorder, conduct disorders, autism, headaches, migraine prophylaxis sleep problems, other codes of interest (including tearfulness and psychosis), irritable bowel syndrome, stress, phobias and obsessive disorders, dissociative disorders and eating disorders.
Statistical analysis Annual incidence rates were calculated using person years at risk (PYAR) as a denominator. For example a person who supplied six months of data to the study would contribute 0. 5 years to the denominator. Poisson regression was undertaken to investigate the adjusted associations between incidence of recorded anxiety symptoms/diagnoses, mixed anxiety depression, panic attack/panic disorder, hypnotic and anxiolytic prescription on the one hand and, year of diagnosis, gender, age group and deprivation on the other. Annual prevalence rates were also calculated utilising PYAR as a denominator. This is a more appropriate unit rather than number of registered cases because each individual's duration of follow-up is not fixed  (Frisher et al. , 2004). The significance of variables in the Poisson regression modelling was assessed using Wald tests.
Sample characteristics There were 311,343 registered GP patients aged 6-18 years between 1st January 2003 and 31st December 2011 in the SAIL databank providing a total of 1,546,489 person years of follow up. The mean follow-up time was 5. 0 years. Annual prevalence of all anxiety subtypes and anxiolytic and hypnotic prescriptions during the study period are shown in Supplementary Tables  1  and 2  respectively. There has been a significant increase in prevalence in all subtype diagnoses and symptoms except mixed anxiety and depression. The prevalence of anxiety diagnosis increased from 1. 97 cases per 1000 person years at risk (95% confidence interval CI 1. 77-2. 20) in 2003 to 2. 53 (95% CI 2. 28-2. 79) in 2011 of 6-18 year olds. The prevalence of anxiolytic prescriptions was 1. 90 cases per 1000 person years at risk (95% CI 1.
Strengths and limitations The main strength of this study is its population based sample size. There is no clear reason to believe the results would differ for the entire population of Wales or the entire population of UK children. The results of the current study reflect trends in presentation to primary care, recognition and treatment by GPs and the way in which depression and anxiety in children and young people is recorded in primary care. However this is likely to be an underestimate of incidence in the community as routine data does not capture individuals who do not present to their GP or, with whom depression or anxiety is discussed, but not recorded. This is common feature of all routinely collected database studies and results are not intended as an estimate of time trends of the population as a whole.
, 2014). In particular trials of benzodiazepines in children and young people with anxiety have yielded mixed results with improvements in anxiety, depression, psychomotor excitation, and hyperactivity, but combined with increased sedation, activation, headache, and nausea  (Simeon and Ferguson, 1987). Other trials have found no statistically significant differences to placebo and concerns remain over disinhibition in children and long term tolerance  (Simeon et al. , 1992). Thus whatever the underlying cause, the increase in anxiolytic prescriptions demonstrated in this study is of concern. There is a need for further research into the safety of these medications, and for specific guidance for treating anxiety disorders in CYP. A recent study from The Health Improvement Network (THIN) databank has found that recording of incident anxiety diagnoses in primary care has declined over recent years with a concurrent increase in incident cases of anxiety symptoms in adults  (Walters et al.
While results here provide a measure of GP recording behaviour, future research may focus on the impact of a diagnosis compared with recording of symptoms on patient outcomes. This would provide further information on the impact of adherence to QOF guidance. The degree of linkage possible utilising the SAIL databank means that outcomes including educational data and hospital admissions could be examined. Future studies may aim to explore whether the way in which a mental health issue is recorded has an impact on care or outcomes for the patient.
Role of funding source This study was funded by the  National Institute of Social Care and Health Research ; Grant number  H07-3-033. It was also supported by the  Farr Institute of Health Informatics Research. The Farr Institute is supported by a consortium of 10 UK research organisations:  Arthritis Research UK , the  British Heart Foundation ,  Cancer Research UK , the  Economic and Social Research Council , the  Engineering and Physical Sciences Research Council , the  Medical Research Council , the  National Institute of Health Research , the  National Institute for Social Care and Health Research (Welsh Government ) and the  Chief Scientist Office (Scottish Government Health Directorates). MRC  Grant no:  MR/K006525/1. The funding sources did not have any influence on study design, collection, analysis or interpretation of data, or the preparation, review or approval of the manuscript.
, 2012; Ward et al. , 2012). A de novo transcriptome of L. perenne was obtained by the assembly of cDNA reads. A de novo assembly was performed using model species data as there is no reference genome available for L. perenne. Differential expression of genes and functions were analyzed in parallel with metabolic data in order to obtain a functional insight of molecular regulations induced by low-intensity chemical stress. Our present study shows that, taken together, the effects of pesticide treatments on metabolites and gene expression strongly suggest that low levels of pesticides, whether as single molecule treatment or as mixture, interact, even in the absence of major physiological impact, with plant cell functions as carbohydrate regulations and signaling. The characterization of plant/xenobiotic direct interactions with signaling and hormone cross-talk effects, which is a major field of research in animal toxicology  (Frye et al.
Assembly and Read Processing Read filtering and final assembly were performed using the Galaxy instance  (Goecks et al. , 2010). The 454 reads were processed to remove sequences below 250-bp and above 1000bp. Reads were improved according to quality and by removing adapter sequences, undetermined bases ("N") and poly-A/T tails. For generation of the reference transcriptome, selected clean reads from all libraries were pooled and assembled to improve mRNA lengths and produce a global library. Reads were assembled in contigs using the de novo assembly program Trinity  (Haas et al. , 2013). Trinity is an Illumina/Solexaspecialized transcriptomic assembler, which is suitable for nonstrand-specific and single-end-read data. According to  Ren et al. (2012) , it gives the best performance among the multiple de Bruijn graph assemblers, and represents an alternative solution for reconstructing full-length transcripts from 454 reads.
The assembly was conducted using the default parameters. Reads were ascribed to contigs using RSEM (RNA-seq by expectation-maximization) software and filtered according to the reads per kilobase of target transcript length per million reads mapped (RPKM) values equal to 1 or greater. After a first Trinity assembly, the unmapped (172,634 total unmapped sequences), and unused reads, were submitted again to the Trinity program, leading to a new assembly. Reads that again did not fit into contigs (42,351 unmapped reads) were defined as singletons. These unique sequences were added to the 14,811 unique contigs to constitute the reference transcriptome. The resulting singletons and contigs represented the candidate unigene set.
Annotation and Functional Analyses After assembling, tBLASTx alignments (e < 10e-5) against The Arabidopsis Information Resource (TAIR, http://www. arabidopsis. org. gate1. inist. fr) databases were undertaken and unigenes with the highest sequence similarity were functionally annotated using Blast2GO  (Conesa et al. , 2005)  with cutoff e-values of 10e-5 (Blastx) and 10e-6 (mapping). Blastbased annotations were complemented with domain-based annotations using the Inter-ProScan tool (v5). Functional classification of unigenes was based on Blast2GO analysis. Pathway assignments were carried out according to KEGG database (Kyoto Encyclopedia of Genes and Genomes (KEGG) resource; http://www. kegg. jp/ or http://www. genome. jp/kegg/). The statistical assessment of Gene Ontology (GO) term enrichments after xenobiotic treatments in comparison to control condition was performed [Fisher's Exact Test with multiple testing correction; false discovery rate (FDR) < 0.
Differential Expression Analysis In order to determine differentially expressed (DE) genes between the 4 conditions, the DESeq method was used. This in silico normalization method is included in the DESeq Bioconductor package  (Anders et al. , 2013). As each condition was represented by a single sample of pooled individuals, the differential expression for each gene was estimated by using the variance of expression for this gene across the 4 conditions. Unigenes were considered as DE at p < 0. 05.
All samples were run in duplicate for each primer set. Specific primers for each gene selected for analysis were designed according to 454 sequences using Primer3 software  (Rozen and Skaletsky, 2000 ; Supplemental Table  1 ). The results of the analysis were treated with Gene Expression version 1. 1 software. Relative expressions were assessed in relation to the stable expression level of the GAPDH housekeeping gene  (Furet et al. , 2012).