dataesr/scientific-paragraphs-categorization huggingface dataset:
QUANTIFICATION AND STATISTICAL ANALYSIS Image Analysis Volocity software (PerkinElmer) was used for analysis and processing of confocal images. For co-localization analysis of confocal images, we used Manders' Coefficient. All experiments were repeated at least three times. The background was fixed for all within-experiment analyses. Volocity software was also used for the Z stack reconstruction; the images presented also include the isosurface rendering in which there is no transparency and colocalized pixels do not appear as yellow. For analysis of SIM images, final visualisation and video production was performed in Volocity 6. 3 Software using isosurface rendering of selected cropped regions of the datasets. Isosurface rendering was used to more clearly visualise the shapes of fluorescent structures within the complex fluorescence volume datasets.
Statistics Significance levels for comparisons between two groups were determined with t test (2-tailed). *= p % 0. 05; **= p %0. 01; ***= p%0. 001. A p value of 0. 05 was considered as the borderline for statistical significance. For experiments where we have considered data from multiple independent experiments, we have normalised control data and used 1-sample t tests. For LC3-II blots, we have normalised both basal and bafilomycin A1 data. For some experiments where we have assessed colocalizations in different conditions or western blot analysis, we have reported data from representative single experiments and noted cell numbers in the legends. This approach was used to minimise effects of heterogeneity between experiments. Excel and Prism 7 software were used for statistical analysis and generation of graphs.
01, ns, not significant. The numbers indicate the LC3-II/GAPDH value of the shown experiment. (L) Ribbon representation of LC3B (PDB code: 5w9a) docked onto the PH domain of dynamin (PDB code: 5a3f). LC3B is colored green and PH domain of dynamin is colored cyan. Conserved LC3 residue R70 is colored in magenta and K51 is colored in orange. DNM2 W525 residue is colored in yellow. The figure was prepared using the program PyMOL (http://www. pymol. org). (M) HeLa cells were transfected for 20 h with pEGFP-LC3-WT, K51A, or R70A. Immunoprecipitates obtained by GFP-TRAP were processed for immunoblot for DNM2. P62 was used as control. The histograms show the amount of DNM2 or P62 co-immunoprecipitated with EGFP-LC3, normalized for the amount of LC3 immunoprecipitated. Data are mean ± SD (n = 3 graphs represent means of the triplicates from three independent experiments).
ACKNOWLEDGMENTS We thank  Matthew Gratian  and  Mark Bowen  for technical assistance;  Antonina Andreeva  ( MRC Laboratory of Molecular Biology, Cambridge, UK ) for useful discussions;  Tamotsu Yoshimori  ( Osaka University, Japan ),  Mark McNiven  ( Mayo Clinic and Mayo Graduate School Rochester, Minnesota, USA ), and  Anne Simonsen  ( Institute of Basic Medical Sciences-University of Oslo ) for kindly providing reagents; and the  Institute of Myology  ( Centre of Research in Myology, UMRS 974, F-75013, Paris, France ) for providing the human fibroblasts from patients. We are grateful to the  UK Dementia Research Institute  (funded by the  MRC, Alzheimer's Research UK , and the  Alzheimer's Society)  (D. C. R. ), the  Roger de Spoelberch Foundation  (D. C. R. ),  Specialist Programme  from  Bloodwise  ( 12048 ), the  UK Medical Research Council  ( MC_U105161083  to  Alan J.
Design Protocol and Specificity-Based Principles of the Duplex Real Time qPCRs The mitochondrial gene encoding for the cytochrome c oxidase subunit 1 (cox 1 gene) was targeted for its presence in several copies by cell and described as a "barcode gene" for filarial nematodes  [26]. PCR design was performed according to the criteria for primers and probes protocol  [27]. Briefly, primers and probes of two duplex qPCR assays (Table  1 ) targeting filarial nematodes and C. grassii DNA (i. e. , CanFil-C. grassii) and those of C. bainae and Cercopithifilaria sp. II (i. e. , C. bainae-C. sp. II), were designed by alignment of sequences from representative members of Onchocercidae family available from GenBank database, using primer3 software v. 0. 4. 0 (http://primer3. ut. ee). Subsequently, all possible combinations of forward-reverse and probe-reverse of each qPCR system were checked within the DNA databases of metazoans (taxid:33208), vertebrates (taxid:7742), bacteria (taxid:2), Canidae (taxid:9608), Felidae (taxid:9682), and humans (taxid:9605) using primer-BLAST  [28].
Limit of Detection and Efficiency Assessment The analytical sensitivity of the newly developed qPCRs was assessed using a serial 10-fold dilutions of both single-species and spiked DNAs. The DNA of O. lupi and C. grassii as well as the spiked DNA from both species were used for the duplex qPCR CanFil-C. grassii while the DNA from C. bainae and Cercopithifilaria sp. II and the spiked DNA samples were used for the duplex qPCR C. bainae-C. sp. II. The sensitivity of each assay was assessed by generating the standard curves and by analyses of the derived parameters (i. e. , efficiency, slope, Y-intercept, and correlation coefficient) within CFX Manager Software Version 3  [29].
Phylogram was edited using iTOL v4 software  [35]. Standardization of the assays was performed on two different panels of canine samples (i. e. , blood and tick samples). However, because the gold standard tests (dog necropsy, blood concentration test and tick dissection) were absent, filarial true-positive dogs were considered if at least one DNA sequence was obtained from at least one sample (i. e. , tick or blood) of each dog. However, samples that had yielded unreadable DNA sequences (overlapping peaks in the electropherograms) from both tick and blood samples of the same dog were removed from the analysis. Finally, prevalence, correct classification, misclassification, sensitivity, specificity, false positive rate, false negative rate, positive and negative predictive value, and Youden index were calculated for each approach  [36] [37] [38].
Phylogenetic analysis confirmed the molecular identification of each filarial detected from blood and/or tick samples by clustering the representative sequences within the clades of the same reference species (Figure  2 ). DNA sequences generated during the present study were deposited in GenBank under the accession number from MW138005 to MW138035. Accordingly, all filaria-positive samples by the qPCR were also amplified by filaria generic PCR [Pan-fil cox 1 PCR]. High quality DNA sequences were obtained from 17 (23. 61%) blood samples, including 14 (19. 44%) D. immitis, two (2. 78%) D. repens and one (1. 39%) A. reconditum and 14 (19. 44%) tick samples, including nine (12. 5%) D. immitis, two (2. 78%) D. repens, one (1. 39%) A. reconditum and two (2. 78%) Cercopithifilaria sp. II. Whilst five (6.
94%) and 10 (13. 89%) samples have yielded unreadable DNA sequences (overlapping peaks in the electropherograms) from blood and ticks respectively (Table  5 ). Phylogenetic analysis confirmed the molecular identification of each filarial detected from blood and/or tick samples by clustering the representative sequences within the clades of the same reference species (Figure  2 ). DNA sequences generated during the present study were deposited in GenBank under the accession number from MW138005 to MW138035. Despite the successful species resolution of the multiplex approach from tick and blood samples of all filarial positive dogs (n = 24), specificity and sensitivity analysis involved only 19 among them (Supplementary Table  S2 ). These latter were considered as filarial true positives dogs, from which at least one DNA sequence was obtained from their blood and/or tick samples (Supplementary Table  S2 ).
Ethics The study was performed in accordance with the requirements of Good Clinical Practice and the Revised Declaration of Helsinki. The study was registered on www. clinicaltrials. gov (NCT02097797). All participants provided written informed consent to participate after receiving verbal and written information about the study. The protocol was approved by the Ethics committee (Comite de Protection des Personnes, CPP), on July 17, 2013. The final authorization was obtained a year later from the French National Security Drug Agency (Agence National pour la Sécurité du Médicament).
Briefly, 16S rRNA gene PCR was performed using 5 ng genomic DNA according to the manufacturer's protocol (Metabiote) using 192 bar-coded primers (Metabiote MiSeq Primers, GenoScreen) at final concentrations of 0. 2 μM and an annealing temperature of 50 °C for 30 cycles. The PCR products were purified using an Agencourt AMPure XP-PCR Purification system (Beckman Coulter), quantified according to the manufacturer's protocol, and multiplexed at equal concentrations. Sequencing was performed using a 250-bp paired-end sequencing protocol on an Illumina MiSeq platform (Illumina) at GenoScreen. Raw paired-end reads were subjected to the following process: (1) quality filtering using the PRINSEQ-lite PERL script  [21]  by truncating the bases from the 3′ end that did not exhibit a quality < 30 based on the Phred algorithm; (2) pairedend read assembly using FLASH (fast length adjustment of short reads to improve genome assemblies) with a minimum overlap of 30 bases and a 97% overlap identity; and (3) searching and removing both forward and reverse primer sequences using CutAdapt, with no mismatches allowed in the primers sequences.
Assembled sequences for which perfect forward and reverse primers were not found were eliminated. The sequences were demultiplexed and quality filtered using the Quantitative Insights Into Microbial Ecology (QIIME, version 1. 9. 1) software package  [22] , and the forward and reverse Illumina reads were joined using the fastq-join method (http://code. google. com/p/eautils). Following an open reference picking strategy, the sequences were assigned to OTUs using the UCLUST algorithm  [23]  with a 97% threshold of pairwise identity and classified taxonomically using the Silva reference database (version 132)  [24]. Principal coordinate analyses of the Bray Curtis distance were performed and used to assess the variation between groups (beta diversity). Significance was assessed using ANOSIM (9999 permutations).
The Shannon and Chao1 diversity indices were calculated using rarefied data (depth = 29,000 sequences/sample) and used to characterize species diversity in a community. Raw sequence data (joined sequences) are accessible in the European Nucleotide Archive (accession number PRJEB33031) and the corresponding metadata file is available in Additional file 3. Sourcetracker, a Bayesian approach, was used to identify sources and proportions of OTUs in the different samples  [25]. Differential analysis was performed using the linear discriminant analysis effect size (LEfSe) pipeline  [26].
Statistical analysis The statistical analysis followed the intention-to-treat approach and results were reported according to the CONSORT statement recommendations. Patients' characteristics were described globally and per group of randomization. Qualitative data were expressed as number (%) and quantitative data were expressed as medians and interquartile range (IQR). The primary outcome was compared between groups with a Fisher's exact test. One primary outcome was missing at 6 weeks (one patient was lost to follow-up) and was replaced by failure. Quantitative variables were compared using a non-parametric Wilcoxon rank-sum tests. The similarity of the fecal microbiota samples was assessed using the Sorensen similarity index (Sorensen similarity index = [1 -Bray Curtis dissimilarity index]).
These data suggest a circular causality between alterations to the gut microbiota and an over-activated immune system, fueled by environmental factors. The current treatments used in IBD do not take into account these new concepts, as they only target the immune actor in disease pathogenesis. FMT studies performed to date may encounter the same pitfall by targeting only the gut microbiota actor. In the current study, we tested for the first time a therapeutic approach targeting both the immune system and the microbiota by first shutting off inflammation with systemic corticosteroids, before reshaping the gut microbiota with FMT. We chose a relatively weak criterion (HBI < 5) to assess the corticosteroid-induced clinical remission as it represented only a step before initiating FMT or sham.
Acknowledgements We thank  URC-Est and CRC-Est  for their strong support. Members of the  Saint-Antoine IBD Network :  Arrivé Lionel ,  Beaugerie Laurent ,  Bourrier Anne ,  Camus Marine ,  Chafai Najim ,  Chambenois Édouard ,  Chaput Ulriikka ,  Martineau Chloé ,  Cholley Monnier Laurence ,  Debove Clotilde ,  Dray Xavier ,  Fléjou Jean-François ,  Hoyeau Nadia ,  Kirchgesner Julien ,  Landman Cecilia ,  Lefèvre H. Jérémie ,  Marteau Philippe ,  Nion-Larmurier Isabelle ,  Ozenne Violaine ,  Parc Yann ,  Seksik Philippe ,  Sokol Harry ,  Svrcek Magali.
Acknowledgements The authors thank the patients and investigators who participated in the study. The authors take full responsibility for the content of the paper. The authors also thank  Saimithra Thammera  and  Uma Kundu  (both of  Medical Communications, Novartis Healthcare Pvt. Ltd. , Hyderabad, India ) for writing assistance, editorial review assistance and in coordinating author review. All authors edited the manuscript for intellectual content, provided guidance during manuscript development and approved the final version submitted for publication. Genentech. She has also received support from the  Lourie Foundation ,  Slomo  and  Cindy Silvian Foundation  and the  Multiple Sclerosis Foundation. D. L. A. received consultant fees from  Acorda Therapeutics ,  Biogen ,  Celgene ,  GeNeuro ,  Genentech ,  F.
It is planned to develop similar systems for other diseases in the future. In addition, the data collected by this system can be used to feed into quantitative models of epidemiological prediction which can be used to support public health decision-making. In 2014, the American Centers for Disease Control and Prevention (CDC) started the Epidemic Prediction Initiative (EPI) that aims to improve the science and usability of epidemic forecasts by facilitating open forecasting projects with specific public health objectives  [70]. Since January 2016, influenza forecasts from participating teams in real time have been published on their website. Although these forecasts have consistently outperformed historical expectations, they are actively developing and testing new models. In Europe, epidemiological data are collected and owned by each country and are generally not publicly available.
ACKNOWLEDGEMENTS The authors would like to thank the speakers, in particular  Robert Cohen ,  Michael Johansson ,  Louise Letley ,  Siff Malue Nielsen ,  David Sinclair ,  Melissa Stockwell ,  Alberto Tozzi  for their input in earlier versions of this paper, and the participants at the meeting for their active involvement in discussions during the meeting. The views and information presented are those of the authors and do not represent the official position of the  U. S. Army Medical Center of Excellence , the  U. S. Army Training  and  Doctrine Command , or the  Departments of Army, Department of Defense, or U. S. Government. Funding. The meeting was funded by the  Fondation Me  ´rieux who received an unrestricted grant from  Sanofi Pasture. Funding for the Rapid Service Fees incurred was provided by  Sanofi Pasteur.
Introduction & Objectives: Lower urinary tract symptoms (LUTS) due to benign prostatic enlargement (BPE) can lead to significant disturbances to health-related quality of life (HRQoL) and psychological well-being. There is variability in the relationship between individual symptom severity and the bother reported by patients as symptom scores alone, may not capture their actual impact on men. The aim of this study was to evaluate the effect of pharmacological treatment of LUTS/BPE on disease-specific and generic QoL measures. Materials & Methods: Evolution was a European prospective, multicenter multi-national, observational registry collecting real life clinical data over two years on the management of LUTS/BPE in primary and secondary care. This study investigated disease specific QoL using questionnaires including IPSS Q8, BPH Impact Index (BII) and Patient Perception of Study Medication (PPSM) Q11 PPSM in previously treated and untreated patients with LUTS/BPE.
Costs and Health Utilities Costs were estimated from a national healthcare payer perspective and included treatment costs and health state costs. In the absence of reliable Vietnamese estimates, health state costs were derived from published data in Thailand (20) using purchasing power parity exchange rates  (21). Cost of death was assumed to be zero (regardless of cause), and drug costs were taken from Vietnamese sources. The Vietnamese national insurance payer reimburses medication costs on a case-by-case basis  (22) , and drug pricing in each healthcare unit is based on the procurement price published by the Ministry of Health (Drug Administration of Vietnam) or Social Insurance Office in the last 12 months  (23). Therefore, drug costs were retrieved from the procurement price list published by the Drug Administration of Vietnam (latest version published September 2018).
In order to adjust LYs gained to produce the outcome of QALYs in the model, health-related quality of life data were required to determine the impact of different health outcomes on patient utility. Utility values are measured on an interval scale with 0 reflecting death and 1 reflecting perfect health. As the ADVANCE study did not evaluate health-related quality of life, utility weights were derived from published health-related quality of life estimates using the EQ-5D-5L instrument in Vietnam  (24). Disutility weights were obtained from previous cost-effectiveness studies, notably the Core Diabetes Model  (25). All costs and health state utilities included in the model are presented in Table  3. For costs and utilities, a distinction was made between the year of occurrence and subsequent year for each health state.
The assumed nitrogen content and resulting thermal dose are both shown in Table  1. Gamma doses, mainly from neutron interaction with the experimental system, are tissue-independent and, therefore, are the same for all cell lines. In most of the cases, the thermal dose component remained higher than the gamma dose component (see Table  1 ). The main objective of the irradiations, which was to have a dose mostly due to low-energy neutrons, was achieved. The biological effect of the secondary gamma radiation would be expected to be less than in higher dose rate LINAC irradiations due to the low gamma dose rate. Indeed, this could be expected in long irradiation, because of repair effects. Nevertheless, the RBE of the gamma dose is set equal to 1 due to the lack of data for the studied cell lines at the present dose rate.
Results for Neutron Irradiation Two end-points were studied for the neutron irradiations: survival, by means of clonogenic assay, and proliferation, by using BrdU incorporation assay, around two weeks and four days, respectively, after the irradiation. Figure  4  displays plates for the visual appearance of these assays with A375 cells. Both end-points showed different results when data were fitted following a linear quadratic equation, as shown in Figure  5. The biggest difference between the survival and proliferation curves was observed in the head and neck cancer cell lines. Because a correlation between the two different end-points could not be established, probably because of the time after irradiation at which they are measured, the comparison with photon irradiation, and the calculations of RBE factors are limited to the most common end-point used, which is the long-term survival by clonogenic assay.
As a result of the neutron-induced gamma production in the experimental arrangement, he survival (Sn) that was associated with the neutron dose alone was obtained by the deduction of the gamma effect, as indicated in Equation (2). Table  2  shows the alpha and beta parameters for each one. Figure  6. Clonogenic survival of six cell lines as a function of the absorbed dose (Gy) following irradiation with photons at the medical linear accelerator, Sγ, with neutrons at the ILL beam, SILL, and, derived, ILL neutrons alone, Sn. Sγ for U87 from  [27]  and Sγ for SQ20 from the one obtained for Cal33. The data were obtained from between two and seven individual experiments after photon irradiation and neutron irradiation. Cells were seeded in triplicate for each data point in each experiment. The U87 cell line was not photon irradiated and the results from Bayart et al.
[27] , obtained with a Varian NDI 226 X-ray tube of 200 kVp (kilovolt peak) at a dose rate of 1. 2 Gy/min, were used. Clonogenic survival of six cell lines as a function of the absorbed dose (Gy) following irradiation with photons at the medical linear accelerator, S γ , with neutrons at the ILL beam, S ILL, and, derived, ILL neutrons alone, S n. S γ for U87 from  [27]  and S γ for SQ20 from the one obtained for Cal33. The data were obtained from between two and seven individual experiments after photon irradiation and neutron irradiation. Cells were seeded in triplicate for each data point in each experiment. The U87 cell line was not photon irradiated and the results from Bayart et al. [27] , obtained with a Varian NDI 226 X-ray tube of 200 kVp (kilovolt peak) at a dose rate of 1. 2 Gy/min, were used.
Discussion Data showing the biological response of low-energy neutron irradiation show marked variability for the six cell lines studied. Therefore, it is crucial to characterize and understand the weighting factors for specific tissues and avoid having to assume such values. The proliferation and survival curves obtained following neutron irradiation seem to be different in most cell lines. Although this fact could suggest contradictory results depending on the end-point selected, the proliferative ability of the viable cells was assessed four days after irradiation while the clonogenic assay estimated the long-term cell survival. Moreover, proliferative and clonogenic potential do not have to necessarily correlate, as different factors may influence attachment, proliferation, and growth, such as cell density and cell-cell contact.
This difference is expected, since, by definition, they are the maximum values of the weighting factors in the low-dose limit. It is important to point out that this does not mean a higher biological dose, because of the different use of the weighting factor in this iso-effective formalism. The accuracy of the photon irradiation data is important when used as a reference radiation in the comparison with neutrons for the RBE estimation. A common type of reference photon radiation, at a specific dose rate, would be desirable. Irradiations at the medical linear accelerator at dose rates of few Gy/min. are a good option in acquiring data for the reference photon dose, providing a comparison with a standard irradiation field for which there is a lot of clinical experience. Because the U87 and SQ20 cells were not available for photon irradiations, the reference irradiation used is not from the same series of irradiation at the LINAC, like the other cell lines.
Implications of all the available evidence Since 95% of participants can be safely treated with ivermectin during any given test-and-not-treat campaign, not having to repeat quantification of microfilarial density the following year would enable substantial savings in time and money. individuals require repeat testing? Data previously collected from 238 individuals with an initial L loa microfilariae density of less than 20 000 microfilariae per mL indicated that none was at risk of SAEs 1 year after receiving ivermectin. 9 uring a second TaNT campaign that was run in Okola between March and May 2017 (around 18 months after the initial campaign), we aimed to investigate changes in L loa microfilarial densities after the first treatment in 2015, at the individual and community levels.