dataesr/scientific-paragraphs-categorization huggingface dataset:
Our study has several strengths, including a relatively large sample size compared to previous DTI studies r Sleep Quality and White Matter r r 5471 r examining insomnia, a battery of established cognitive tests spanning three major cognitive domains, and longitudinal data on sleep quality over 5 time-points spanning, on average, 16 years. However, there are also a number of limitations. For example, all sleep measures examined were self-reported. Discrepancies between subjective and objective sleep measures have been described  [Buysse et al. , 2008] , and objective measures of sleep may be more sensitive to cognitive deficits  [Cavuoto et al. , 2016]. Also, the high proportion of men and high education level within our sample will limit the generalizability of results. In conclusion, we found that current poor sleep quality was associated with a pattern of reduced FA and increased AD and RD in a sample of community-dwelling older adults.
29 n this study, we sought to elucidate whether ADAM9 contributes to lung cancer progression and its mechanisms. Based on a cohort of patients with lung cancer, bioinformatics analysis of databases has revealed that there is a trend between (overall or free relapse) survival and ADAM9 gene expression. An in vivo metastatic model and angiogenesis experiments (in vitro and in vivo) were developed to assess the roles of the ADAM9 protein in metastatic and angiogenic processes. These observations provide strong evidence that ADAM9 plays a crucial role in the aggressiveness of adenoma lung cancer and that it might be an effective target for future therapies in metastatic nonsmall cell lung cancer (NSCLC).
In vitro angiogenesis assay Supernatants from TrA549 control cells and TrA549 A9cells exposed or not exposed for 18 h to PMA (50 ng/mL) were recovered. Extracellular (EC) matrix gel was used according to the manufacturer's protocol. HUVECs (2 × 10 4 cells/well) were cultured in 96-well plates with the supernatant of each cell type. The HUVECs were then examined using calcein. Tubular structure formation within the matrix was assessed 22 h later using a fluorescence microscope. The total length of the new capillary structures was measured using ImageJ software (National Institutes of Health (NIH), Bethesda, Maryland, USA). Overall, five pictures were taken per well, and the experiments were performed three times.
On day 45, the mice were sacrificed. The lungs and the brain were removed and embedded in paraffin and were then sliced in the middle and at the bottoms of all blocks. The slices were stained with haematoxylin and eosin for routine histological examination. The percentage of pulmonary invasion was calculated as the ratio between the total sizes of the metastases within the total size of the lung using ImageJ software. For this analysis, three tumour sections were cut, one at the top, one in the middle and one at the back. Overall, five representative pictures were taken per available field.
Immunohistochemistry and quantification of microvascular density Paraffin-embedded fragments of the tumour species were sectioned (5-μm thicknesses). Sections were pre-incubated with 2% bovine serum albumin in PBS for 1 h, and then, the primary anti-CD31 antibody was added and incubated for 45 min (1:50; Abcam). The sections were incubated with HRP-conjugated anti-rabbit secondary antibody (1:250; Dako, Glostrup, Denmark). After development with diaminobenzidine solution (Vector Laboratories Burlingame, CA, USA), the sections were counterstained with haematoxylin. Sections were evaluated under a microscope (Olympus BX60; Olympus, Tokyo, Japan) at 20× magnification and analysed with ImageJ software (NIH). Blood vessel density was quantified by counting the total number of CD31-positive vessels across the entire section of the tumour.
Bioinformatics The associations between the gene expression levels and NSCLC patient prognosis were obtained from the PrognoScan database (http://www. prognoscan. org/). PrognoScan is a large collection of publicly available cancer microarray datasets with clinical annotations and a tool for assessing the biological relationships between gene expression and prognosis. In the PrognoScan database, the association of gene expression with the survival of patients was evaluated using the minimum p value approach and the corrected p value. Briefly, patients were first arranged by expression levels of a given gene. They were then divided into high-and low-expression groups at all possible cutoff points, and the risk differences between any two groups were estimated by the log-rank test. Finally, the cutoff point resulting in the most pronounced p value was selected.
Statistical analysis Statistical analysis was performed using the means of data obtained from at least three independent experiments. All results are presented as the mean ± standard error of the mean (SEM). Student's t test was used to compare significant differences in the experimental values between the two samples. When the analysis included more than three groups, one-way analysis of variance was used (GraphPad Prism; GraphPad Software, San Diego, CA, USA). A p value of 0. 05 was considered to be statistically significant.
Results First, we investigated the correlation between the level of ADAM9 protein expression and overall survival of patients with lung adenocarcinoma using 'Gene expression data for pathological stage I-II lung adenocarcinomas', obtained from the PrognoScan database (http:// www. prognoscan. org/). Data without a corrected p value were not analysed. Two datasets revealed a correlation between a very high ADAM9 expression and overall survival (corrected p < 0. 05; Table  1 , Figure  1 ). In the six other datasets, there is a very high trend for an influence of high ADAM9 protein expression and a poor overall survival. In the last study, there is a negative association but not significant (corrected p = 0. 286). For the correlation of ADAM9 expression regarding relapse-free survival, two datasets were listed and showed that high expression of ADAM9 protein was correlated with a poor relapse-free survival (corrected p < 0.
01; Table  1 , Figure  1 ). Analysis of data from another database (The Cancer Genome Atlas (TCGA) database) supplied similar results (data not shown). To explore the influence of ADAM9 expression in aggressive adenocarcinoma lung cancer, a model of stable downregulation of ADAM9 expression in A549 cells was developed. ADAM9 protein expression was stably downregulated in A549 lung cancer cells with a lentiviral vector carrying ADAM9-specific siRNA (TrA549 A9-). A control sample was produced in A549 cells with a lentiviral control vector (TrA549 ct). Both cell lines were used in subsequent experiments. As shown in Figure  2 (a), high knockdown efficiency was achieved in A549 cells. After 10 h of exposure to PMA, known to enhance the metalloprotease activities of ADAMs, ADAM9 expression was increased in both native A549 cells and A549 cells transfected with the control vector; however, the expression remained low in A549 cells transfected with vectors carrying ADAM9-specific siRNA.
The tissues were stained with haematoxylin and eosin at a magnification of 20×. (c) Evaluation of the pulmonary invasion percentage in nude mice. This percentage was calculated as the ratio between the total size of the metastases and the total size of the lung using ImageJ software (mean ± SD). blocking anti-CXCR2 antibody to the supernatant to measure tube formation, whereas the supernatant from WT A549 cells stimulated with PMA induced 171% increase in the total length of new vessel formation by HUVECs (p < 0. 0001; Figure  6 ), the same experiment performed in the presence of blocking anti-CXCR2 antibody resulted in complete inhibition of this induction (p = 0. 0001). When the same experiment was performed on TrA549 A9-cells, the anti-CXCR2 antibody did not modulate new vessel formation.
Acknowledgements The authors thank  Lorna Saint Ange  for editing. C. M. K. and M. A. performed all experiments and drafted the manuscript. A. T. -S. performed the in vivo experiments and helped in drafting the manuscript. C. C. participated actively in cell cultures and technical aspects in vitro. C. N. -O. participated in the in vivo models and technical aspects and in the design of the in vivo models. F. B. participated in the design of the study and coordination and helped drafting the manuscript. J. A. conceived the study, participated in the design of the study and helped drafting the manuscript. F. L. conceived the study, established the design of the study, participated in the coordination and drafted the manuscript. All authors read and approved the final manuscript. C. M. K. and M.
29 (0. 79-2. 12) Overall survival jacob-00182-UM 202381_at 204 0. 407 0. 153 1. 94 (0. 78-4. 83) Overall survival GSE31210 1570042_a_at 204 <0. 001 0. 014 6. 62 (2. 47-17. 70) Relapse free survival GSE31210 202381_at 204 <0. 001 0. 019 2. 44 (1. 48-4. 03) Relapse free survival GSE31210 1555326_a_at HR: hazard ratio.
Based on these observations, we conducted a second pathway analysis from the full list of differentially methylated metabolic genes given by IPA (Table  4 ). Among 48 genes, we found that 28 hyper-methylated and 11 hypo-methylated genes were directly connected to the in PAH patients (heritable + idiopathic) compared to controls. Two clusters (cluster 1 and cluster 2) were selected in function of the methylation levels (Over-methylated probes in red and under-methylated probes in green). (B) Enrichment analysis of the differentially methylated promoters as canvases (Network2Canvas software). For each canvas, brighter nodes represent lower P-value enriched terms. same network "cholesterol and lipid transport" (Figure  3B ). When we focused on the ten top candidates genes hyper-or hypo-methylated (Figure  3C ), TP53 (tumor protein 53) was presented directly or indirectly as a common denominator of all genes.
By using IGV, public mRNA-expression data from Nextbio, and IPA, we concluded that ABCA1 was a major hyper-methylated promoter or downregulated gene discriminating PAH and control (Figures  5 6 , Table  5 ). ABCA1 belongs to the super-family ATP Binding cassette (ABC) transporters. ABC transporters are important for pulmonary homeostasis, with at least three cases of persistent PH of the newborn due to loss-offunction mutations in ABCA3  [32] [33] [34]. To date, no study    3E , a meta-analysis was performed using the NextBio platform. A pair-wise correlation score was computed between 6 biosets (or studies) related to PAH. According to a disease or tissue, this score determines the highly relevant genes through the normalized rank of the gene in the bioset, the number of biosets containing the gene and the number of studies.
For each pairwise comparison, unsupervised hierarchical clustering was performed with Cluster (v3. 0) using Spearman Rank correlation with a median-centered gene dataset. TreeView was used to generate the heatmaps and to select individual clusters containing hypermetylated or hypomethylated promoters. Pearson correlation coefficients were calculated based on normalised methylation values using the R function cor from the base package. Briefly, the matrix of methylation values with rows corresponding to CpG sites and columns corresponding to samples was limited to CpG sites of interest (all promoters) as well as samples from iPAH or hPAH. Next, the correlation was calculated between the group-wise means of CpG site methylation values. The methylation data reported in this paper have beens deposited in NCBIs Gene Expression Omnibus (GEO) (Omnibus, 2014) and are accessible with the access number (GSE84395).
Integrative genomic viewer (IGV) To visualize the methylation region, we used the IGV tool that enables real-time exploration of large datasets including methylation  [84]. All data files submitted to IGV are represented in horizontal rows called track. Figure  3D -3E display various tracks including the Genome reference Hg19 (RefSeq Genes), all human promoters (gene promoters), all existing CG probes (Illumina CG probes) together with all differentially methylated probes between control and PAH patients (Control vs all). Moreover, additional files from the heatmap analysis were loaded showing the hypo-methylated (cluster 1, Figure  3D ) or hyper-methylated (cluster 2, Figure  3E ) promoters in PAH patients compared to controls. By evaluating the methylation level (numbers of modified probes) for each promoter, IGV allowed us to focus on the most important genes.
FUNDING This work was supported by research grants from  INSERM, National Funding Agency for Research (ANR)  (Grant  ANR-13-JSV1-0011-01 ),  Laboratoire d'Excellence (LabEx) en Recherche sur le Médicament et l'Innovation Thérapeutique (LERMIT) ,  Assistance Publique Hôpitaux de Paris (Département Hospitalo-Universitaire Thorax Innovation) ,  Legs Poix  ( Chancellerie des Universités de Paris ), and  Federal Ministry of Education and Research (BMBF)  (Grant  FKZ-01KX1314 ) and by the  French patient association HTAPFrance. A. H. is supported by a PhD grant from  Région Ile de France (CORDDIM). F. A. is supported by a post-doctoral grant from Aviesan and by  Lefoulon Delalande Institute.
It has been reported that around 17. 8% of patients with diabetes go below the poverty line due to medical OOP payments compared with 13. 9% of patients without diabetes. 14 Previous reports from the International Diabetes Management Practice Study (IDMPS) showed the high resource consumption among patients with T2D from Asia, Latin America, the Middle East and Africa,  15  where the presence of microvascular/macrovascular complications and inadequate diabetes control were strong predictors for hospitalizations. These data highlighted the urgent need for health policy steps to address the increasing magnitude of this ongoing public health problem. In this cross-sectional analysis, we estimated levels of HRU and their predictors among patients with T2D recruited from 18 countries in Africa, the Middle East, South Asia, Eurasia and Turkey.
RESEARCH DESIGN AND METHODS The IDMPS is an ongoing international multicenter observational study conducted annually for the past 10 years. Until now, we have collected six waves of data from non-Western countries to document the pattern of care in a real-world setting in order to inform practice and policy. The primary objective of the study is to assess the HRU of T2D in current medical practice. The secondary objective is to evaluate the initiation, characteristics and management of insulin therapy and to assess the overall health economic impact of T2D and its complications. Specific outcomes collected as part of wave 5 of the IDMPS included details of management of care, education and HRU. Physicians involved in each wave of the IDMPS were randomly selected at a country level and requested to enroll the first 10 patients with T2D they had a consultation with over a 2-week period.
Eligible physicians had to have experience with initiation and titration of insulin. Patients younger than 18 years, patients participating in a clinical study, or patients receiving temporary insulin treatment because of conditions such as gestational diabetes, pancreas cancer or surgery at the time of enrollment were excluded. Patients were also excluded if they had already participated in a previous wave of the IDMPS. The sample size was estimated on a country by country basis, and was calculated such that the expected relative precision around the proportion of patients receiving insulin reached 20%. Each wave of the IDMPS consisted of a cross-sectional and a longitudinal part. The cross-sectional part was a 2-week survey during which data were collected by physicians through a standardized case report form.
Patients enrolled in the cross-sectional study who were treated with insulin were eligible to enter a 9-month longitudinal study. Physician details and characteristics were also collected at study initiation. Ethical approvals for the IDMPS study were obtained from the Ethics Committees in all participating countries and all patients provided written informed consent prior to enrollment. Study design and reporting format are in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. 16 esource consumption data were collected within the cross-sectional part of the fifth wave of the IDMPS study (2011-2012). HRU was assessed based on the patient-reported frequency of visits to endocrinologists/ diabetologists or other physicians (including general practitioners (GPs)), hospitalizations due to diabetes-related complications (including hypoglycemia), hospital inpatient days, and emergency room (ER) visits due to diabetes complications and work loss (unemployment, absenteeism and sick leave) in the past 3 months.
Additionally, patients were asked to report the frequency of ER visits due to hypoglycemia in the past 6 months and number of laboratory tests (glycated hemoglobin, HbA1c), selfmonitoring of blood glucose (SMBG) and screenings for complications in the past year. Details on antidiabetic treatment (eg, oral antihyperglycemic drugs (OADs) by class and agent, insulin by class and agent, or other) with the corresponding doses and frequencies of administration were recorded. Similar information on use of antihypertensive and lipid-lowering drugs was also recorded. Presence of complications was recorded by the physician using definitions included in the case report form. Levels of HRU were estimated among the 18 countries stratified according to regions including South Asia, Eurasia, the Middle East and Africa with data for Turkey presented separately, due to its geographical location and demography.
Variables which were significant at a 20% threshold were included in the multivariate model. A backward selection method was then applied, with the final model restricted to variables statistically significant at the 5% level as well as the country. Complete case analysis, which involves the discarding of cases where the dependent variable or any of the identified covariates are missing, was applied as the base-case. Countries with a sample size lower than 50 were excluded from the HRU multivariate analysis and this concerned only one country (Senegal). Incidence rate ratios (IRRs) and corresponding 95% CIs were generated from the multivariate analysis for each categorical covariate included in the model. All statistical analyses were performed using SAS V. 8. 02 (SAS Institute, Cary, North Carolina, USA).
38 40 espite the increased HRU and costs associated with diabetes, certain care items are considered beneficial. For example, increases in screening for complications, HbA1c testing, SMBG, diabetes education and medication use are linked to positive long-term health benefits and can lead to cost savings. 41 42 In a recent analysis of a large clinical laboratory database, patients who had three-monthly measurements of HbA1c were found to have the best glycemic control. 42 In a 7-year prospective survey of Chinese patients with T2D, lack of monitoring of HbA1c and/or lipids was associated with a 15-fold increased risk of death compared with those who had at least one measurement. 43 In wave 1 of the IDMPS, a high level of general education was associated with increased likelihood of attaining the HbA1c goal (<7%).
CONCLUSION In the IDMPS wave 5, T2D was associated with high levels of HRU among patients in Africa, the Middle East, South Asia and Eurasia. Macrovascular/microvascular complications and insufficient glycemic control were the most consistent parameters associated with such HRU. These findings are consistent with previously reported IDMPS data collected between 2006 and 2007 indicating a persistent need for change on a healthcare system level. While these data re-emphasize the importance of early diagnosis and intervention to reduce complications and HRU, more national-based surveys with precise separation of HRU for prevention and treatment of late complications will be needed to inform healthcare providers and policymakers regarding the socioeconomic burden of diabetes and its complications.
We collected data for study villages at 2 time points: during December 2011-February 2012 and during December 2012-February 2013. These times were chosen to align our surveys with the season that has a high incidence NiV infection in Bangladesh  (12). Trained data collection teams used hand-held devices to identify the latitude and longitude of the randomly selected points and enrolled the village with that coordinate or the village located closest to that point as a control village. Teams visited case and control villages and identified a group of key village informants who assisted with mapping the village boundary and estimating the number of households located in each village. The teams then asked local residents to identify all of the bat roosts they knew of in their village and within 5 km of the village boundary.
Trained data collectors located all of the roosts and counted the number of Pteropus bats roosting. In addition, they counted all date palm sap trees in the village and within 500 m of the village boundary. We then requested that 25 randomly selected households from each village participate in a structured survey. After identifying the village boundary, the field team used a random number table to choose a cardinal direction: north, east, south, or west. The household on the edge of the village in that direction was approached for participation. The team then divided the estimated number of households in the village by the desired sample size  (25)  and skipped that number of households to choose the next for participation. This process continued until 25 households were enrolled. For villages with <25 households, all households were enrolled.
Data Analysis To estimate the number of persons in each village, we multiplied the number of estimated households in each village by the mean number of household residents in households sampled for the study from that particular village. We measured data for each village by direct observation, such as the number of bats roosting, or through the surveys at sampled households. We compared case villages to both sets of controls in terms of human and bat population size, as well as human behavior patterns regarding date palm sap and fruit consumption. We estimated means and proportions with 95% CIs and compared case and control villages by using generalized linear models with binomial distributions and a logit link, which used robust variance estimates to account for model misspecification. For exposures measured at the household level, we accounted for clustering within the village in the model.
Analyses were conducted by using the generalized linear model package in Stata version 13. 0 (StataCorp LLC, College Station, TX, USA). Variables that were highly skewed were log-transformed to equalize leverage. We used multivariable logistic regression models to estimate independent associations (odds ratios with 95% CIs) between village characteristics and being a village with a case of NiV infection. For multivariable regression, each village had 1 value for each exposure, and householdlevel data from each village was aggregated to estimate the proportion of all village households reporting each exposure or behavior. Therefore, we did not need to account for clustering of observations, but we did calculate the 95% CIs for the odds ratios by using robust variance to account for imprecision in exposures estimated from a sample of households.