dataesr/scientific-paragraphs-categorization huggingface dataset:
The present study evaluated whether this revised scoring system, which was developed for IFNb and evaluated over the short term,  8  was able to predict disability outcomes for up to 7 years in patients treated with teriflunomide, a once-daily oral immunomodulator approved for the treatment of relapsing-remitting MS (AUBAGIO; Sanofi Genzyme, Cambridge, MA), using data from the TEMSO extension study (NCT00803049). METHODS Study population and design. TEMSO was a multinational, multicenter, randomized, placebo-controlled, double-blind, parallel-group phase 3 study in patients with relapsing forms of MS. 9  In the core study (NCT00134563), 1,088 patients were randomized 1:1:1 to receive once-daily oral placebo (n 5 363), or teriflunomide 7 mg (n 5 366), or 14 mg (n 5 359), for 108 weeks. Key inclusion criteria allowed for enrollment of patients aged 18-55 years who met the McDonald 2001 10 criteria for relapsingremitting MS with or without progression, had an Expanded Disability Status Scale (EDSS) score of #5.
Data are presented for the combined teriflunomide 7-and 14-mg groups (n 5 552). Standard protocol approvals, registrations, and patient consents. TEMSO was conducted in accordance with the Inter- national Conference on Harmonisation Guidelines for Good Clinical Practice and the Declaration of Helsinki. The protocol was approved by central and local ethics committees. Patients provided written informed consent before the commencement of TEMSO and, again, before entry into the extension. Clinical Trial (clinicaltrials. gov) identifiers: TEMSO, NCT00134563; TEMSO extension, NCT00803049. Defining scoring categories. The MAGNIMS score is a recently published scoring system 8 that classified patients after 1 year of treatment with IFNb for the risk of disease progression according to the occurrence of relapse (0 to $2) and new and enlarging T 2 w lesions (,3 or $3) on 12-month MRIs.
In preparing this large-scale experiment, a 1:6 scaled water experiment (see Figure  4a ) was built and utilized in order to gain insight into the flow structure and the pressure field for varying Reynolds numbers and precession ratios (Poincaré numbers). Parallel to that, the spectral element code SEMTEX  [52]  was qualified and intensely used for precession-driven flows in cylinders. While such simulations are restricted to Reynolds numbers of about Re = 10 4 , the large experiment will reach approximately 10 8. The 1:6 water experiment reaches a number of 1. 6 × 10 6 when run at 10 Hz, but can also be slowed down to reach a value of 10 4 , thereby guaranteeing some overlap with numerical simulations. A significant share of simulations and experiments was invested into estimating the pressure field, a crucial input for the (static and dynamic) strength evaluation of the vessel.
Another result concerns the rigorous mathematical link between the non-normal growth factor of purely hydrodynamic rotating flows with the normal growth rate of the HMRI which gives -to the best of our knowledge -the first link between non-normal growth and diffusive (or dissipation-induced) instabilities. We should also mention here the recent astrophysical application of AMRI for explaining the angular momentum redistribution of post-main sequence low-mass stars  [84]. Many problems related to the TI liquid metals were investigated in close collaboration with the project B3 which was dedicated to applied problems of liquid metal batteries  [85, 86, 87]. As one of the potentially dangerous instabilities, which would occur even if electrovortex flows and sloshing instabilities were completely suppressed, the TI was numerically treated with an OpenFOAM code enhanced by a Poisson solver for the electric potential and Biot-Savart's law for the induced magnetic field  [85].
Patients. After excluding samples with incomplete data, a set of 27 CRC patients were gathered for a preliminary study. We selected nine volumes of data from each ABC type, where a volume of data was structured in 16 multispectral images (Figure  1 ). Thus, images were filtered by an average filter (spatial filter) before further segmentation processing to minimize the effects of noise in images and other external factors. All the images were reconstructed to a 512 × 512 matrix where the volume size of 512 × 512 × 16 was taken into consideration in texture feature extraction from GLCM of ABC (Figure  2(a) ).
Each segmented cell was histogram equalized to 32 levels, and then we employed the GLCM computation. The foremost advantage of GLCMs applied to volumetric data is the ability to capture intensity relationships between the pixels in a 3D volume. Further, the number of GLCMs resulting from 3D operations is typically smaller than that corresponding to numerous 2D slices. For example, in a data cube with 10 separate 2D slices, there are a total of 80 GLCMs (8 GLCMs analogous to 2 offsets and 4 directions per slice). On the other hand, in a 3D operation, the total number of GLCMs is 26 (13 directions and 2 offsets). Supported by the benefit of GLCMs applied on volumetric data, we computed GLCMs of multispectral ABC and quantified these cooccurrence matrices by Haralick features. 2. 4. 2. Texture Quantification.
Conclusion In this paper, a new method based on multitexture features for abnormal cell classification of colorectal cancer is proposed. Real data of colorectal cancer was used to validate the discrimination between ABC features. ABC was segmented by active contour technique and then texture feature extracted from GLCMs. Significant texture features were selected based on ANOVA test. The best results were obtained when combining all features together and PCA was applied to get five PC features with accuracy of 92. 59% to discriminate between ABC types. This result is promising to make a bride between image features and colorectal pathology which would lead to efficient medical diagnosis and treatment.
Analysis of nuclear-encoded OXPHOS genes using BeadArrays Total RNA was converted to cDNA (200 ng) and then biotinylated cRNA according to the protocol supplied with the Illumina TotalPrep-96 RNA Amplification Kit (Ambion). Previously we studied disease pathway changes in AD, MCI, and control subjects by hybridizing blood RNA to Illumina HT-12 V3  (Lunnon et al. , 2012) , which is deposited in the Gene Expression Omnibus (GEO) (batch 1, GEO accession number GSE63060). For the current study we used an independent set of subject samples that were hybridized to Illumina HT-12 V4 according to the manufacturer's protocol (batch 2, GEO accession number GSE63061). Gene expression values were obtained using Genome Studio (Illumina). In total, 370 individuals had genome-wide expression data generated in leukocytes using the Illumina HT-12 V4 expression BeadArray.
For the purposes of the current manuscript only the 240 nuclear-genome expressed probes relating to mitochondrial function were analyzed. Quantitative Real-Time PCR (qRT-PCR) was used to measure gene expression levels of 12 mitochondrial-genome expressed transcripts in 509 individuals. This included 181 of the 370 individuals for whom genome-wide expression data are presented in this manuscript, and an additional 272 of the 329 individuals for whom we previously published genome-wide expression data  (Lunnon et al. , 2012 (Lunnon et al. , , 2013  Preprocessing and analysis of data quality including background correction and normalization were performed in R using the Bioconductor packages, Lumi (Gonzalez de  Aguilar et al. , 2008) , MBCB  (Allen et al. , 2009) , and SVA  (Leek et al. , 2012).
Analysis of OXPHOS protein subunits using Luminex Briefly, buffy coat samples were lysed using red cell lysis buffer, followed by centrifugation and removal of the supernatant. The pellet was resuspended in 300 mL of Cell/Mitochondria Lysis Buffer (Human Oxidative Phosphorylation Magnetic Bead Panel), premixed with an EDTA-free Protease Inhibitor Cocktail (Roche). Following mixing on ice for 30 minutes, the lysate was centrifuged at 14,000 g for 20 minutes at 4 C. The concentration of protein in the supernatant was measured using the Nanodrop 1000 Spectrophotometer (Thermo Fisher Scientific). The MILLIPLEX MAP Kit Human OXPHOS Magnetic Bead Panel was used according to the manufacturer's protocol (EMD, Millipore). This 6-plex immunoassay measures key proprietary subunits in complexes IeV. Data from each sample were normalized using nicotinamide nucleotide transhydrogenase measured in the same assay.
Data were log transformed and technical outliers >2 standard deviations from the mean were removed. The effects of age, sex, and collection site were regressed out of the data within R, and residuals were compared between diagnostic groups using linear models, with post hoc t tests. Further details are provided in the Supplementary Methods. 2. 6. Analysis of mtDNA copy number using qRT-PCR Total genomic DNA was prepared (Qiagen blood DNA kit) from 100 mL of whole blood collected in EDTA-coated vacutainer tubes. It was pretreated by sonication prior to extraction and DNA extracted according to the manufacturers protocol (Qiagen blood DNA kit). Samples were assayed in triplicate using the QuantiTect SYBRgreen PCR kit (Qiagen), using primers complementary to unique regions and genes of the mitochondrial genome (thus not amplifying nuclear mitochondrial DNA sequences) and the single copy nuclear gene beta 2 microglobin in the presence of reference standards, as previously described  (Malik et al.
Acknowledgements The authors would like to thank the participants and their families for generously taking part in this multicentre biomarker study. The authors would also like to thank the MSc students  David Robinson ,  Jessica Tebbutt ,  Philip McGuire ,  Wendy Hyun Jung Sung , and  Carmen De Soria  for conducting the real-time PCR and Luminex assays under the supervision of A. H. , K. L. , and J. R. The authors would like to thank  Rufina Leung ,  Megan Pritchard ,  Belinda Martin ,  Kathryn Lord ,  Nicola Dunlop , and  Catherine Tunnard  for sample collection and neuropsychiatric assessments at the London site. This work represents independent research part funded by the  InnoMed (Innovative Medicines in Europe ) an  Integrated  Project funded by the  European Union  of the  Sixth Framework program  priority  FP6-2004-LIFESCIHEALTH-5 ,  Alzheimer's Research UK ,  The John  and  Lucille van Geest Foundation , the  Rosetrees Trust , the  National Institute for Health Research (NIHR) Biomedical Research Centre and Dementia Unit at South London and Maudsley NHS Foundation Trust and King's College London  and the  National Institute for Health Research University College London Hospitals Biomedical Research Centre.
The views expressed are those of the author(s) and not necessarily those of the  NHS , the  NIHR , or the  Department of Health. A. H. receives support from the  Innovative Medicines Initiative Joint Undertaking  under EMIF grant agreement no115372, resources of which are composed of financial contribution from the  European Union 's  Seventh Framework Programme  ( FP7/2007e2013 ) and EFPIA companies in kind contribution. R. D. is supported by awards to establish the  Farr Institute of Health Informatics Research at UCL Partners , from the  Medical Research Council, Arthritis Research UK ,  British Heart Foundation ,  Cancer Research UK, Chief Scientist Office, Economic and Social Research Council, Engineering and Physical Sciences Research Council ,  National Institute for Health Research, National Institute for Social Care and Health Research , and  Wellcome Trust  (grant  MR/K006584/1 ).
In contrast to LPLD, dysbetalipoproteinemia usually only manifests itself later in life. Furthermore, precipitating factors (such as decompensated diabetes, weight gain, new medications, etc) are usually detectable. In the case of more than one mutation in one of the candidate genes being present, a family screening or a PCR-cloning based analysis is necessary in order to assess simple or compound heterozygosity. In the case of mutations in the LPL gene, two studies are available to support clinicians and geneticists in assessing pathogenicity of the identified variants: details of mutations along with a mutation map of the causative genes are described in the Western Database of Lipid Variants  [32]  and a second classification is available based on screening performed with a microarray LPL chip  [11].
Methods This study was undertaken at the West China Hospital of Sichuan University with the approval of the human ethics review committee. We conducted a retrospective analysis of all patients with recurrent DFSP diagnosed from 2010 to 2016. Written informed consent was obtained from all patients or patients' parents for their clinical data to be used. All patients were admitted into our hospital owing to recurrence of DFSP after a previous surgery performed elsewhere. Recurrent DFSP was defined as tumor regrowth at the original tumor site at least 6 months after the resection. Clinical records were independently reviewed by two investigators. Clinical information, including demographics, clinical presentation, laboratory results, treatment, histopathological findings, follow-up examinations and outcome, was obtained.
In all cases, diagnosis was independently confirmed by two expert pathologists. Based on the histopathological findings, we divided DFSP into 2 types: fibrosarcomatous DFSP (FS-DFSP) and ordinary DFSP (O-DFSP)  (10). Statistical analyses of the study were conducted using SPSS 21. 0 for Windows (SPSS Inc, Chicago, USA). Student's t-test was used to analyze the quantitative data. The Fisher exact test was used to compare qualitative variables. P values less than 0. 05 were considered significant.
gov identifier NCT00474994). In a recent systematic review, the authors found that the mean time to recurrence was 5. 7 years after MMS  (8). In the present study, we found that the mean time to recurrence was 2. 93 years after simple excision. Interestingly, we found the mean time to recurrence of FS-DFSP was shorter than that of O-DFSP. Multiple studies have reported that FS-DFSP was more aggressive form of DFSP than O-DFSP  (20, 22). This difference may explain why FS-DFSP presented a shorter time to recurrence. Although none of our patient had local recurrence and metastases after being treated with MMS, there is insufficient data, at our institution and in the literature, in reporting long-term follow-up data in order to ensure the efficacy of MMS in recurrent DFSP. Therefore, further efforts are needed to evaluate the definite effect of MMS on recurrent cases.
TBVAC2020 is a research project supported by the Horizon 2020 program of the European Commission (EC). It aims at the discovery and development of novel tuberculosis (TB) vaccines from preclinical research projects to early clinical assessment. The project builds on previous collaborations from 1998 onwards funded through the EC framework programs FP5, FP6, and FP7. It has succeeded in attracting new partners from outstanding laboratories from all over the world, now totaling 40 institutions. Next to the development of novel vaccines, TB biomarker development is also considered an important asset to facilitate rational vaccine selection and development. In addition, TBVAC2020 offers portfolio management that provides selection criteria for entry, gating, and priority settings of novel vaccines at an early developmental stage.
The TBVAC2020 consortium coordinated by TBVI facilitates collaboration and early data sharing between partners with the common aim of working toward the development of an effective TB vaccine. Close links with funders and other consortia with shared interests further contribute to this goal. iNTRODUCTiON One hundred years ago, Albert  Calmette (1863 Calmette ( -1933) )  and Camille Guérin (1872-1961) had almost reached their goal  (1). They had passaged Mycobacterium bovis 200 times at 14 d intervals on potato slices soaked with ox gall in their attempt to generate an attenuated vaccine against tuberculosis (TB). They had started their program in 1906 and had already obtained preliminary evidence for safety and protection of their candidate in 1913. Yet, they continued until they had completed the 230th passage before verifying its efficacy and safety in experimental animals including guinea pigs, rabbits and non-human primates (NHPs) as well as in the natural host, cattle.
Over the last 10 years, the TBVAC/NEWTBVAC consortia have conducted many standardized head-to-head preclinical animal studies in mice, guinea pigs and NHPs. The data arising from these studies have facilitated vaccine selection  (63, 64). This WP takes this successful approach a step further and applies it to early clinical testing. Furthermore, there is an opportunity provided by this WP to embrace human experimental medicine studies, where early clinical trials can be used to demonstrate proof-of-concept. An example of this would be the evaluation of the safety and immunogenicity of a recombinant viral vector delivered by aerosol, compared with systemic administration  (65).
PROCeSS FOR vACCiNe SeLeCTiON Vaccine candidates are selected for inclusion in this WP by the PMC, in conjunction with the TBVI P&CDT. This advice is independent of the vaccine developer. TBVI and Aeras have agreed on a set of portfolio management criteria which include stage-gating criteria  (7, 34) , and these criteria are used to guide vaccine selection in this WP4. The data arising from the trials conducted as part of this WP4 will be reviewed by the PMC for subsequent decisions about progression to safety and immunogenicity trials in TB high burden countries. Ongoing interactions with The European & Developing Countries Clinical Trials Partnership (EDCTP) and clinical sites in Africa, including those that are part of the EDCTP Networks of Excellence, will ensure that, subject to full and independent peer review, promising candidates are progressed as efficiently and effectively as possible in an endemic setting.
Complementary to these efforts is the discovery of new TB BMs, using innovative approaches (#3 in Figure  2 ). A long-term goal is to move the best performing correlates forward toward validated immune correlate assays, ideally in the format of point-of-care tests for use in areas with high TB burden. Future activities will include active engagement of assay developers. Finally, the WP5 is building a database to capture the most important (transcriptomic) TB BMs (#4 in Figure  2 ), and there are close interactions between this WP and other efforts in this area.
Partners have expertise in downstream assay development such as lateral flow assays  (86)  and simplified transcriptomic assays  (71). Recent novel work on mathematical modeling of vaccine immune responses has shown that models can predict dose-response relationships  (93). An important point is that TB BM assays may need to be adapted to specific types of TB vaccines (e. g. , live vs. subunit) or depending on the antigen and delivery system selected. This may necessitate "tailor made" sets of BMs, for which TBVI is setting up a BM Development Team (BDT). Finally, WP5 is building a TB transcriptomic biomarker database, to be a helpful resource for the TB BM community to provide a basis for "tailor made" TB vaccine biomarker selection, and to complement a TB diagnostic BM database as a valuable resource for future research  (94).
ACKNOwLeDGMeNTS Many thanks go to  Katja Grunow  and  Souraya Sibaei  for excellent editorial help and to  Diane Schad  for excellent graphical support. We also thank  Robert Golinski  for critical reading of the manuscript. This project has received funding from the  European Union 's  Horizon 2020 research and innovation programme  under grant agreement No. 643381.
Met Sequences of archaeal tRNA i Met were extracted from the tRNAscan-SE database  (Lowe and Eddy 1997). A sequence logo  (Schneider and Stephens 1990; Crooks et al. 2004 ) calculated from a multiple alignment of the 170 extracted DNA sequences shows a high level of conservation among archaeal initiator tRNA sequences (Fig. 1 ). For instance, S. solfataricus tRNA i Met deviates from the consensus by only 13 positions. Interestingly, the sequence of a mutated E. coli Met-tRNA f Met carrying A 1 -U 72 instead of C 1 :A 72 appears to be close to the archaeal consensus, with 13 deviations only (83% identity). In particular, the sequences of the acceptor stems are identical. Therefore, the E. coli tRNA f Met A 1 -U 72 variant appears to be a good mimic of an archaeal initiator tRNA i Met.
Overall structure of tRNA f Met A 1 -U 72 and crystal packing analysis The strain described above was then used to overexpress and purify Met-tRNA f Met A 1 -U 72 for use in crystallization trials. Crystals belonging to space group C222 1 were obtained using 20% PEG 6000 and 2 M NaCl as precipitants. The structure was solved by molecular replacement and refined to 2. 8 Å resolution. All bases are visible except C 75 and the methionylated A 76. An analysis using DSSR  (Lu et al. 2015 ) identifies all the secondary structure elements characteristic of the classical cloverleaf secondary structure as well as usual tertiary interactions that stabilize the L-shaped tertiary fold of the molecule. A global superimposition of the present structure to that of wild-type E. coli tRNA f Met (PDB entry 3CW5)  (Barraud et al.
However, despite this movement, the network of interactions in the anticodon loop is conserved in the two tRNA structures. An unusual A 1 -U 72 pair Characteristic of eukaryotic and archaeal initiator tRNAs, the A 1 -U 72 pair at the top of the acceptor stem, shows a peculiar conformation (Fig. 5 ). Watson-Crick (WC) interactions between A 1 and U 72 are unexpectedly not observed. When compared to a standard G 1 -C 72 WC base pair, as in tRNA Phe (PDB entry 1EHZ  [Shi and Moore 2000] ), a rotation of the A 1 base around bond P-O3 ′ is observed. Moreover, instead of adopting the usual anti conformation, the adenine ring rotates around the glycosidic bond and adopts a syn conformation (χ = -14. 9°) (Fig. 5A, B ). The 5 ′ phosphoryl group folds back into the major groove of the acceptor stem and interacts with the N7 atom of G2 (Fig.
Crystallization, data collection, structure solution, and refinement Crystals belonging to space group C222 1 were obtained using the sitting drop method with a 1:1 mixture of a 50 µM solution of Met-tRNA f Met A 1 -U 72 and 20% PEG 6000, 2 M NaCl as precipitants. Final pH of the 1:1 mixture of tRNA and precipitant was 6. 3. Interestingly, the C222 1 space group was never observed for crystals of wild-type E. coli initiator tRNA f Met. According to the CC(1/2) values (Table  1 ) the high-resolution limit of the data set was 2. 8 Å  (Karplus and Diederichs 2012; Diederichs and Karplus 2013). The structure was solved by molecular replacement using PHASER and the coordinates of E. coli tRNA f Met (PDB entry 3CW5  [Barraud et al. 2008] ) from which the terminal CCA bases have been removed. Initial map showed different orientations of the anticodon region and of the 3 ′ extremity of the acceptor helix as compared to the molecular replacement-starting model.
Cycles of manual reconstructions, performed with the program COOT  (Emsley et al. 2010) , and of refinements steps with PHENIX  (Adams et al. 2010) , led to a model refined to 2. 8 Å resolution (R work = 0. 196, R free = 0. 225). Because of crystal packing interactions, the tRNA molecules are more tightly bound together along the acceptor helices. This is reflected by lower B-values along the acceptor helix comparing with those observed for atoms belonging to the anticodon helix. According to this anisotropy, the TLS procedure  (Adams et al. 2010)  was used in the last steps of refinement. All nucleotides are visible except A 76. Moreover, positioning of C 75 is only tentative. Refinement parameters in Table  1  were calculated with PHENIX.