dataesr/scientific-paragraphs-categorization huggingface dataset:
0, 15 mM NaCl, 0. 01% Tween 20) for 3 h and incubated overnight at 4 • C with primary antibodies (anti-PANX1, 1:800; anti-PANX2, 1:350; anti-PANX3, 1:1000). Membranes were then washed with TBS-T and incubated with corresponding secondary horseradish peroxidase-conjugated antibodies (1:10,000) for 1 h. The anti-GAPDH antibodies are used as the loading control (1:10,000). Immunodetection was performed using chemiluminescent substrate Luminata Forte (Merck Millipore) and LAS-3000 imaging system (Fujifilm, Tokyo, Japan). Densitometric analysis of signals was carried out using ImageJ software (version 1. 39o, National Institutes of Health, Bethesda, MD, USA). Preliminarily to expression experiments, positive controls samples were used to further validate the banding pattern of each antibody (Figure  S2 ).
Patients Between January 2008 and September 2015, we conducted an observational study and retrospective analysis of children born between 25 and 42 weeks gestational age (GA) with LSV hyperechogenicity on CUS. The analysis was unicentric and carried out in a French tertiary reference center. Exclusion criteria were infants with congenital abnormalities of the central nervous system, severe other congenital abnormalities, chromosomal and metabolic disorders or had an abnormal CUS with findings other than isolated LSV. Follow-up was completed (57/58, 98. 2%) for all but one patient. The medium age of follow up was established at the time of data collection.
Methods Retrospective data were retrieved from our center through the newborns' medical files. The perinatal variables studied were: maternal serologic status (toxoplasmosis, rubella, syphilis, human immunodeficiency virus (HIV), Cytomegalovirus (CMV)), alcohol or drug intake, gestational diabetes, autoimmune disease, eclampsia, administration of corticosteroids, magnesium sulphate or Rovalcyte, type of pregnancy, presence of transfuser-transfused syndrome parental and consanguinity. The neonatal variables studied were the duration of pregnancy, birth weight, Apgar, mode of delivery, serologic the newborns' serologic status (toxoplasmosis, rubella, syphilis, HIV, CMV, listeria, herpes simplex virus (HSV)) in order to conclude that congenital infection is not related to LSV, existence of congenital malformation, Trisomy 21, AFHR (abnormal fetal heart rate) neonatal hypoglycemia, dysthyroidism, perinatal asphyxia, and the need for ventilator support.
, dependent on the measurement direction) and the lack of structural information. In order to correct any geometric distortion of the head and accentuation of the intracranial vasculature on echo-planar images, we used shorter TE at higher field strengths. The child's neurodevelopmental outcome was gathered through clinical examination data and/or data provided by the child's pediatrician. Moderate-severe neurodevelopmental impairment was defined as ! 1 for moderate to severe cerebral palsy (CP was defined according to Bax  8  ; referred to a number of non-progressive conditions involving predominantly motor deficiencies of varied semiology, secondary to cerebral anomalies occurring during the development of the brain. This condition includes varying degrees of muscle tone, posture, voluntary movement, and automatic movement disorders); moderate to severe cognitive delay (assessed per behavior disturbance) severe visual impairment, defined as visual acuity, 6/60 (metric scale) in the better eye; or severe hearing impairment, defined as requirement of unilateral/bilateral hearing aids or cochlear implants.
Statistical analysis Data were analyzed using SPSS for Windows. A p-value of less than 0. 05 was considered statistically significant. Categorical variables were described by frequencies and percentages, and continuous variables were described by means of standard deviation or medians and maximum/ minimums. Comparative analysis is done using Chi-2 or Fisher test for qualitative variables, and Student test or analysis of variance tests for quantitative variables. ManneWhitney & KruskalleWallis tests were used when the previous tests were not applicable.
03) and in neonates who needed respiratory support at birth (p Z 0. 002). Table  3  reports perinatal and outcome data according to the age at which the LSV was discovered. Early onset LSV (<7 days of life) were found in 67. 2% of our cohort. The rate of early or late LSV was not significantly different in the preterm population as compared to the term infant. Nevertheless, in the group of children born before 32 weeks GA, the rate of late LSV was significantly higher than early LSV (p < 0. 001). A cerebral MRI was performed on 35 patients (60. 1%), with 54. 2% being performed on prematurely born children. After being completely informed about the MRI procedure and objectives, parents had the option to decline authorizing the examination (n Z 10). One patient was lost to follow-up and 11 patients were transferred to another neonatal unit.
Genome-wide singlenucleotide polymorphism (SNP) array, focusing on cAMP-related genes, compared ten tetrads of samples, each tetrad containing leucocyte DNA from the proband and its 2 parents plus adrenal tumor DNA from the proband. This allowed identification of the 2q31-2q35 locus as the largest LOH region in the dataset. Located in this locus, PDE11A appeared as an obvious candidate gene because of its inclusion in identified allelic losses The cAMP/PKA signaling pathway in the adrenal cortex. (A) The cAMP/PKA signaling pathway in normal adrenocortical cell. Adrenocorticotropic hormone (ACTH) binds to its G protein-coupled receptor MC2R, resulting in Gs protein activation, which further activates adenylyl cyclase (AC), resulting in enhanced cAMP production. PKA is a hetero tetramer, composed of 2 regulatory subunits (R) and 2 catalytic subunits (C).
Overview The SPRINTT trial is a phase III, single-blind, multicenter RCT (ClinicalTrials. gov identifier: NCT02582138) that is being conducted to compare the efficacy of a MCI program (i. e. , physical activity, nutritional counseling/dietary intervention, and ICT intervention) versus a healthy aging lifestyle education (HALE) program for preventing mobility disability in older persons with PF&S. The MCI and the HALE intervention are thoroughly described elsewhere  (Landi et al. , 2017; Marzetti et al. , 2017). Like in LIFE  (Pahor et al. , 2014) , the primary outcome of mobility disability has been operationalized as incident inability to complete the 400-m walk test  (Simonsick et al. , 2001). Secondary outcomes of SPRINTT are detailed elsewhere  (Landi et al. , 2017). The SPRINTT RCT is currently being conducted in 16 sites, located in 11 European countries, under the coordination of the Department of Geriatrics at the Università Cattolica del Sacro Cuore (Rome, Italy) (Table  1 ).
Preliminary, unpublished analyses performed on existing data during the SPRINTT preparation phase showed that aLM BMI detected more instances of sarcopenia in overweight or obese older adults. Conversely, the crude aLM criterion was more effective at identifying sarcopenia in individuals with normal or low BMI. Whether the differential performance of the two FNIH criteria reflects the existence of gender-specific sarcopenic phenotypes it will be established through pre-planned secondary analyses at the end of the project. In summary, we have described a population of non-disabled older persons with clear physical impairment specifically linked to muscle loss. These individuals with unmet medical needs are sufficiently prevalent and easy to detect in the community that may represent an ideal target for pharmacological and non-pharmacological interventions against sarcopenia and physical frailty.
Acknowledgements The present work was funded by a grant from the  Innovative Medicines Initiative -Joint Undertaking  ( IMI-JU 115621 ). The work was also partly supported by the nonprofit research foundation " Centro Studi Achille e Linda Lorenzon " and by intramural research grants from the  Università Cattolica del Sacro Cuore  ( D3. 2 2013  and  D3. 2 2015 ). The authors thank all the participants and the staff involved in the trial for the enthusiastic participation and dedication.
The tip of each Pasteur pipette was inserted into the airflow tube through a small hole. For each sensillum, the ten-compound blend (Table  1 ) was tested first, and if a spike burst was detected, the compounds, dichloromethane control, and octanal were then tested individually at 3 min intervals  [25]  in a randomized order. The SSR-signals were recorded for 6. 0 s, starting 2. 0 s before stimulation. A Syntech Universal AC/DC probe was used to record the signal (amplified 10×) captured by the tungsten electrode. This signal was fed to a PC via a Syntech IDAC 4 amplifier. Autospike software (Syntech, v. 3. 9) was used to record and analyse all data. The sampling rate was set to 2400 Hz, the pre-trigger to 2 s, and the pulse duration to 1 s. A filtering range of 200 Hz to 2 kHz was applied, and 50/60 Hz suppression was enabled.
2 EGTA, 2. 5 ATP-Na 2 , and 0. 5 GTP-Na 2 plus 0. 05% neurobiotin (Vector Laboratories), dextran tetramethylrhodamine (10,000 MW, fluoro-ruby, 0. 01%; Life Technologies), pH 7. 4 and osmolarity 290 -300 mOsm, ranged from 7 to 10 M⍀. Whole-cell patch-clamp recordings were performed using Clampex 10 software connected to a Multiclamp 700B amplifier via a Digidata 1440A digitizer (Molecular Devices). Voltage-clamp data were low-pass filtered at 3 kHz and digitized at 10 kHz. Series resistance was monitored throughout the experiments and was not compensated. Data were discarded if series resistance varied more than Ϯ 20 M⍀. Passive membrane properties of lamina II i interneurons were studied in the current-clamp mode. Membrane input resistance (R m ) and membrane capacitance (Cm) were determined from the slope of the linear portion of the I-V relationship by repeated hyperpolarizing current injections with stepwise increasing amplitudes (Ϫ40 to Ϫ10 pA, 800 ms pulse duration).
21 m. Image analyses and quantifications were performed using Fiji ImageJ version 1. 51 software (http://rsbweb. nih. gov/ij). PKC␥/pERK1/2 cell counting in lamina II i of MDH. z-stacks with ϳ30 photomicrographs per stack (starting at surface of slice; step size of 0. 38 m; magnification 40ϫ) were scanned from two to three parasagittal 350 m slices per animal. The number of pERK1/2 and/or PKC␥-IR interneurons in the interval from 10 th to 30 th steps (7. 6 m thickness) for each confocal section was counted and average per animal. Great care was taken to ensure that the immunostaining of each PKC␥ and pERK1/ 2-IR interneuron was clearly defined. Only cells that had clear unequivocal labeling were counted. Data were expressed as the mean of the total number of labeled cells of five animals per group.
Statistical analysis All data are presented as the mean Ϯ SEM. The number (n) of animals or neurons used for each analysis is showed in the corresponding figure or table. All graphs and statistical analysis were realized on GraphPad Prism version 7. 04 software and Statistica version 10. 0 software. Parametric statistical tests were used to compare different experimental groups (normality distribution of data was assumed). Paired Student's t test was used to analyze statistical significance between two groups (see Fig. 5D , Table  2 ). The t-values were expressed with their associated degrees of freedom (t df ). When three groups and only one factor were compared, we used one-way non-repeated-measures ANOVA followed by Tukey's HSD post test (see Figs. 2B2, 3B, 4B, 5B, 6 A, B, D, F,H2, 7 A, B, D, F ).
085; p ϭ 0. 998 CFA vs vehicle; Fig. 6A ). However, CFA injection significantly  Data represent mean Ϯ SEM of morphological and structural characteristics of (n) 3D-reconstructed neuritic arbors of neurobiotin-labeled PKC␥ ϩ interneurons recorded in ex vivo MDH slices from vehicle, CFA (subcutaneous injection into the vibrissa pad: 2. 5 mg/kg), and after bath application of TCB-2 (10 M, 5-HT 2A R agonist) or 5-HT (10 M). 4F4PP (100 nM, 5-HT 2A R antagonist) was administered intracisternally 30 min before CFA. Neuritic 3D reconstructions were performed from parasagittal slices (350 m thick). Data represent mean Ϯ SEM of morphological and structural characteristics of (n) 3D-reconstructed neuritic arbors of neurobiotin-labeled PKC␥ Ϫ interneurons recorded in ex vivo MDH slices from vehicle, CFA (subcutaneous injection into the vibrissa pad: 2.
PRC-related transcriptional network Hierarchical clustering of the p-value matrix corresponding to all positive probes after 48h of serum induction revealed groups of genes co-regulated by several transcription factors (Figure  2-1 ). This approach also showed that each of the factors could be individually positive for independent genes. Few genes (n=82) were positive only for PRC suggesting that other transcription factors than those we studied interact with this coactivator. The combination of the six factors was associated to promoter regions of 43 genes. One group of genes (n=354) was related to five factors: PRC, ERR1, GABP, CREB and NRF1. Two main groups associated the PRC/ERR1 complex to either CREB/NRF1 (686 genes) or to GABP (246 genes). The Gene Ontology Database was queried using GoMiner software and p-values were computed for each GO term based on the Fisher's exact test  [14].
PRC SiRNA and cDNA microarray analyses Total RNA was extracted using Trizol LS reagent (Life Technologies) following the manufacturer's recommendations. cDNA microarray slides were prepared at the Biogenouest Genomics Core Facility of the University of Nantes (France), using a set of 20,000 oligonucleotides with full functional characterization and content referencing (OciChip microarrays and Ocimum Biosolutions, Hyderabad, India). mRNA amplification from non-transfected cells, PRC SiRNA and scrambletransfected cells, cDNA labelling and hybridization were performed using protocols described by manufacturers (GSE14282 in NCBI's Gene Expression Omnibus). Bioinformatics analysis has already been described in our previous study  [7]. Gene ontology enrichments in gene lists were determined using GOMiner.
MiRNA microarray profiling MiRNA was issued from the Trizol-extracted fractions of PRC SiRNA and scramble-transfected XTC. UC1 cells after 48h of 20% serum induction. Microarrays were manufactured by Agilent Technologies (Santa Clara, CA, USA) and contained 20 to 40 features targeting each of 866 human miRNAs. Labeling and hybridization of RNA samples was performed according to the manufacturer's protocol. Measures were obtained in triplicate. Microarray results were analyzed using GeneSpring GX 7. 3. 1 software (Agilent Technologies) and are available in NCBI's Gene Expression Omnibus through GEO Series accession number GSE33843. The Agilent algorithms estimated a single intensity measure for each microRNA, referred to as the total gene signal (TGS) calculated by multiplying the total probe signal by the number of probes per gene.
ChIP-chip analysis ChIP assays were performed on 10 6 XTC. UC1 cells/assay after 24h and 48h of 10% serum induction following the protocol provided by the manufacturer (EZ-ChIP, Upstate, Merck) after crosslink by 1% formaldehyde and sonication. These time-points were selected to ensure complete transcriptional effect of PRC and to address posttranscriptional regulation. Depending on the factor two or three antibodies were tested and antibodies were selected based on two criteria: successful use in previous relevant ChIP studies and/or the relevance of identified functional ontologies or targeted genes. Functional ontologies were either described in the literature or confirmed by our previous PRC-related transcriptomic study  [7]  using GSEA software to identify over-represented transcription factor binding sites in co-expressed genes  [32].
Next, WGA amplicons were applied to Agilent Human Promoter ChIP on chip arrays 244K, containing 17,000 60-mer probes per array (Agilent Technologies, Santa Clara, CA, USA) also including miRNA gene promoters. The labeling of DNA samples for ChIP-chip analysis was performed using procedures previously described  [34]. The arrays were scanned at 5-μm resolution on a scanner G2505C (Agilent Technologies) and signal intensities from the IP and the input fractions were compared after normalization. The data are accessible through GEO series access number GSE 106597.
Considering replicates for each transcription factor, the final positive probes were selected using the two distinct p-values (pVal1 and pVal2) as follows: The motif discovery task was performed on positive probes with flanking masked sequences of 200 bp. Then, the MD module in the TFBS tools (R package) allowed discovering motifs of 7 to 18 bases length  [35]. In order to eliminate the redundancies between all the discovered motifs and to compare them with Jaspar and Transfac databases, the T-Reg Comparator tool was used  [36]. Similar motifs were gathered leading to the definition of a consensus motif. Statistical significance for these motifs was computed regarding their score distribution in a set of positive and negative probes with a Chi-square homogeneity test  [37]. Gene ontology enrichments for positive genes on ChIP-chip were determined using GOMiner.
Aim Although emergency medical service (EMS) utilisation is increasing internationally, the factors driving this increase have not been well quantified using a large EMS dataset. We sought to describe long-term trends in EMS utilisation in Victoria, Australia. Method We conducted a retrospective observational study of consecutive patients presenting to the state-wide EMS in Victoria, Australia between 01/01/2010 and 31/12/2015. We calculated incidence rates of EMS presentations using Victorian population estimates, and conducted time-series regression analysis, adjusted for temporal trends and population size. Results A total of 2,923,815 EMS patient presentations were included. Patient presentations grew by an average of 4. 3% per annum, compared with 2. 0% annual growth in the Victorian population.
Panel 2 Real-world evidence definition and dimensions Definition: Real-world evidence (RWE) "entails data collection and analysis about the use, benefits and risks of medicines that fall outside the bounds of the classic Randomized Clinical Trial, including use of data that is routinely collected in the daily practice of medicine, and thus reflective of the heterogeneous patients seen in real world practice settings. " (http://catalyst. phrma. org/realworld-evidence-not-just-big-data). RWE data categories according to the Network of Excellence in Health Innovation (http://www. nehi. net/ writable/publication_files/file/rwe_issue_brief_final. pdf) Claims data derived from insurance reimbursements Clinical trials data derived from the outcomes of randomized clinical trials Clinical setting data derived from patient medical records and patient care Pharmacy data derived from prescription orders and fulfillments Patient-powered data derived directly from the patient experience Real-world evidence on the political agenda: The National Institutes of Health in the United States has inaugurated the Precision Medicine Initiative and a series of Open Data initiatives.
, camera, environmental sensors) To explore the full scope of current use of ICT for functional outcomes in dementia (including prodromal stages), we additionally performed a search of clinical databases (accessed in November 2017) using the string ((dementia With respect to (1), the use of standard actigraphy is well established. However, Table  1  and Panel 3 illustrate that wearable sensing devices beyond actigraphy are able to provide additional relevant end points in future RCTs. With respect to (2), few studies so far have used ubiquitous and unobtrusive ICT solutions to monitor long-term behavior; one example is the determination of factors that influence time out of home in older adults using up to 1 year of in-house sensor-based monitoring  [47]. If monitored over long periods of time, a sensor intended to control lighting.
In this study, detailed data on finegrained motor behavior in urban wayfinding was recorded using WIMS and global positioning system for 13 people with dementia. A set of energy-and kinematics-based features was developed with the objective to achieve real-time detection of episodes of disorientation in the WIMS data stream. Machine learning using a cross-validated compound feature set based on WIMS was able to detect effects of spatial disorientation (area under the curve. 74), even without correcting for knowledge where behavior change can be expected due to transition points such as road crossings. Complementary to wearables, sensing devices that do not require any instrumentation of the user also provide potentially relevant data: Example 3 (video, indoor, long-term clinical 1 short-term functional): A study by Konig et al.
[18]  analyzed the performance of everyday activities (such as "prepare medication" or "use phone") on image processing algorithms applied to video recordings of these activities. The researchers used an Event Monitoring System to automatically extract information about patient's performance (e. g. , feet position, number of steps, and the activities carried out). Extracted features were used as input for a Na€ ıve Bayes classifier to classify the participants in two dimensions: (1) degree of autonomy (good, intermediate, and poor) as a functional end point; and (2) cognitive status (AD dementia, mild cognitive impairment, and healthy). The Event Monitoring System reached highly accurate autonomy and cognitive group classification benchmarked by established clinical instruments. Such system, due to its use of video data and an experimental environment, is applicable as an objective measure of functional level in clinical trials, but not likely to be used as home assessment.
As a result, most consumers do not read terms of agreement or privacy policies of ICTbased resources, which leads to the routinization of consent, where the act of agreeing to the use of a technology becomes unreflective and uninformed  [91]. Moving forward, it will be imperative to exercise transparency in the provision of RWE ICT solutions and to carefully consider, with the help of the dementia community, how to best preserve end-users' autonomy while ensuring safety  [92]. Following the concept of citizen science, ownership of ICT-based sensor data obtained outside of the framework of clinical trials require a regulatory approach where the data remain with the user or patient, and technical solutions are provided to allow the user to opt-out of any reuse proposed to them. Linked with this approach, calls of public sponsors for new ICT platforms for RWE collection may ask a regulated access to ICT and portlet algorithms by a formal procedure to speed the validation process.
Acknowledgments S. T. is supported by grants from the  Federal Ministry of Research (BMBF) ,  Germany , ( 01GQ1425B ,  16SV7091 ,  16SV7348K ) and the  Marie-S. Curie Innovative Training Network BBDiag  ( EU-Horizon2020 Project ID: 721281 ). C. B. is supported by the  Marie-S. Curie Innovative Training Network BBDiag  as well. J. K. is supported by grants from the  National Institute on Aging  ( R01 AG042191 ,  P30AG024978 ,  P30AG008017 ,  U2CAG054397 ). F. K. is supported by the  German Research Foundation (DFG) ,  Germany  ( CRC 1270 ). T. K. is supported by grants from the  Federal Ministry of Research (BMBF) ,  Germany , ( 16SV7091 ,  16SV7349 ,  03ZZ0519D ). J. H. is supported by  AGE-WELL NCE Inc. , the  Canadian Consortium on Neurodegeneration and Aging , the  Alzheimer's Association  (grant number  ETAC-14-321494 ) and the  Natural Sciences and Engineering Research Council of Canada (NSERC).