dataesr/scientific-paragraphs-categorization huggingface dataset:
Acknowledgements The authors would like to express their sincere gratitude to the funding agencies supporting this research, including; the  Swedish Research Council, Swedish Heart-Lung Foundation ,  Marianne and Marcus Wallenberg's Foundation ,  Swedish Medical Society, Swedish Foundation for Strategic Research ,  Karolinska Institutet  and Sk ane  University Hospital Funds. IMPROVE was supported by the  European Commission  (Contract number:  QLG1-CT-2002-00896 ),  Swedish Heart-Lung Foundation, Swedish Research Council  (projects  8691  and  09533 ),  Knut and Alice Wallenberg Foundation, Foundation for Strategic Research, Stockholm County Council  (project  592229 ),  Strategic Cardiovascular  and  Diabetes Programs of Karolinska Institutet and Stockholm County Council ,  European Union   Framework Program  7 (FP7/2007-2013) for  Innovative Medicine Initiative  under grant agreement n°IMI/115006 (the  SUM-MIT consortium) ,  Academy of Finland  (Grant # 110413 ),  British Heart Foundation  ( RG2008/08 ,  RG2008/014 ) and  Italian Ministry of Health  ( Ricerca Corrente ).
~50 patients have been seen with excellent patient satisfaction response and reduced time to treatment. ~20% patients had major change in treatment plan following multi-disciplinary evaluation. Additional efforts to develop a central BM database along with clinical and translational research programs are on-going. CONCLUSIONS: Establishment of a multi-disciplinary BMC to facilitate care and centralize research programs addresses a critical need for coordinated patient-centered BM management. This endeavor has enhanced patient experience through multi-specialty collaboration. Our program demonstrates the feasibility and effectiveness of a dedicated BMC in the treatment of this complex patient population.
Systemic therapy was tiered into 4 categories: chemotherapy, immunotherapy, hormonal therapy, and targeted therapy. All images were manually reviewed by two radiation oncologists specializing in brain tumors to assess the presence versus absence of radiographic necrosis. Patients with radiographic necrosis who harbored associated neurologic symptoms or were managed with steroids/bevacizumab/resection were considered to have symptomatic radiation necrosis. Data were analyzed using univariable Cox regression in SAS v9. 4. The median follow-up in surviving patients was 1. 79 years. RESULTS: In total, 252/429 and 361/429 patients received systemic therapy pre and/or post SRS, respectively. Patients receiving systemic therapy ≤5 days before SRS displayed higher rates of radiographic (HR 2. 48, 95% CI 1.
BACKGROUND: The evaluation of response for brain metastases (BM) may be challenging in the context of treatment by stereotactic radiotherapy (SRT) or immunotherapy or both. METHODS: We reviewed clinical and neuroimaging data of 62 melanoma patients with newly diagnosed BM treated by the combination of immunotherapy and SRT (n=33, group A), immunotherapy alone (n=10, group B) or SRT alone or in combination with other systemic therapies (n=19, group C). Response was assessed using RECIST 1. 1, RANO or iRANO criteria. RESULTS: BRAF mutations were noted in 26 patients. 54 patients (87%) had 1-3 metastases. The median DS-GPA was 3. After a median follow-up of 30. 5 months, 39 patients have experienced  CNS progression, 16 (48. 5%)   29% ) in group A, 0 (0%) in group B, 5 (29. 5%) in group C. Response rates were similar with all three sets of response criteria.
Cell culture Human tissue specimens were recovered from post-mortem or amputated healthy subjects and patients with grade IV OA, aged 52. 5 ± 8. 5 years and 74. 4 ± 5. 1 years, respectively. The study was approved for OA specimen recovery by the French Ministry of Research and Innovation and the Personal data Protection ethics Committee (CPP) of Languedoc-Roussillon (approval DC-2010-1185) and CPP of Paris V, Ile de France and the Consultative Committee on the Treatment of Information in Research in Health field (CCTIRS) (approval 15-623-ter). Healthy tissues were recovered after approval by the Agence de la Biom edecine (authorization #: PFS16-006) for post-mortem subjects or for amputated patients (C17-53). Cartilage, bone, synovium and infrapatellar fat pad samples were recovered from the same patients, cut in small pieces and weighted.
To minimise this, an active search for cases eligible for registration was done in specific structures (some dermatologic oncologic multidisciplinary team meetings; some haematology labs; some medical files for outpatients in health care centres). It led to the identification of unreported incident cases. In the following years, the last two pathology labs out of five located in the LA, the main hospitals and two radiotherapy centres located around the LA enrolled in the notification process. The data provided retrospectively to the RLA from 2005 onwards were investigated. Each notification provided dates, International Classification of Disease-tenth edition (ICD-10) codes or the specific pathological code of the affection, and full names, date of birth, sex and address of the subject.
3-Authentication and registration of incident cases Each specific disease code and pathological report was investigated. Medical files were inspected to confirm the registration of a case. All cases were coded and registered according to the rules of the French network of cancer registries (Francim), the European Network of Cancer Registries (ENCR), and the International Association of Cancer Registries (IACR)  [6, 7]. For each case, the date of diagnosis, topography, morphology and basis of diagnosis were recorded as well as the name, forename, date of birth, gender, and address at diagnosis of the patient. Specific software, DEPEdits/IARC Tools, developed by the International Agency for Research on Cancer (Iarc) was used to check the consistency of coding.
5-Analyses Men and women were studied separately. As a preliminary step, a global analysis without covariates[9-11] was performed, assuming that the probability of capture depended only on the sources of ascertainment. Then, analyses incorporating age and place of residence of subjects as possible sources of heterogeneity of capture were undertaken. Estimates from the latter were used to calculate stratified and overall completeness. Log-linear analyses (Poisson regression) were performed using STATA® 11. 0 software (College station, Texas)  [12].
1-Incident cancer cases At the time of national data centralisation (2011 and 2012), 4 446 incident cancers were registered for men and 3 642 for women for 2008 and 2009; 57 of these cases among men (1. 3%, mainly haematological, prostate and skin cancers) and 35 of these cases among women (1%, mainly haematological and skin cancers) had not been notified. The distribution of age and place of residence of the notified and non-notified cases according to gender are presented in Table  1. The distribution of notifications by gender is shown in Figure  1. The HCC source notified almost all cases (91. 8 and 93. 9% of cases among men and women respectively) whereas the L source notified the fewest cases (48. 7 and 51. 8% of cases among men and women respectively).
Circular dichroism Circular dichroism (CD) spectra were recorded on a JASCO-815 spectropolarimeter using 1-cm path length quartz cuvettes at 20 • C. Scans from 220 to 320 nm were performed with a scanning speed of 100 nm/min, 1-nm data pitch, 1-nm bandwidth and 1 s digital integration time (DIT). For each measurement, an average of three scans was taken, the spectral contribution of the buffer was subtracted and data were zero-corrected at 320 nm. DNA samples with concentrations of 3-8 M were prepared in a buffer containing 70 mM KCl, 20 mM KPi (pH 7). Molar ellipticity of the CD spectra was calculated using the DNA concentration derived from the sample absorbance at 260 nm.
Crystallization TBA-T-Block2 solution at a concentration of 1 mM was prepared in 100 mM potassium cacodylate buffer (pH 7). Prior to using for crystallization, the sample was annealed by heating at 95 • C for 5 min followed by slowly cooling to room temperature. Initial screening for crystallization conditions was done at 24 • C using Natrix 1 & 2 reagents set (Hampton Research) in a 96-well sitting drop vapor diffusion setup at both 2:1 and 1:1 sample-to-reagent proportions with the help of mosquito ® LCP (ttplabtech). Rod shaped crystals were found to form within 7-10 days under the following condition: 0. 08 M potassium chloride, 0. 04 M sodium cacodylate trihydrate pH 7. 0, 60% (v/v) -2-methyl-2,4-pentanediol and 0. 012 M spermine tetrahydrochloride. Crystals were flash frozen in liquid nitrogen before data collection.
X-ray diffraction data collection and refinement Crystal diffraction data were collected at the PROXIMA 1 beamline of the SOLEIL synchrotron, France. Native datasets were collected over 360 • rotation ranges at 0. 1 • oscillation range (Table  2 ). Data was processed using the XDS software package  (42). Initially, the data were processed in P2 1 space group. Molecular replacement was done using the Z-G4 crystal structure (PDB ID: 4U5M) as a search model to obtain initial phases. Two copies per asymmetric unit were found. Reconstruction in the molecular replacement density map clearly indicated the presence of one right-handed and one left-handed block. The model was iteratively built through cycles of refinement using Phenix  (43, 44)  and manual rebuilding in Coot  (45). However, the refinement could not be improved beyond R work and R free values of 23 and 27%, respectively.
This result indicated the formation of a four-layered G4 structure as well as classified the guanines into either outer tetrad layers or inner tetrad layers. Note that the imino proton of G8 was not observable suggesting its involvement in one of the G4 loops. The NOESY spectrum performed at 200 ms mixing time in H 2 O displayed four sets of guanine H1-H8 connectivity patterns in the imino-aromatic proton region (Figure  2A ), showing that the G4 core structure was comprised of four G-tetrads, G2  2B ). Combining the NOESY data with the solvent exchange results, we deduced that the overall structure can be divided into two blocks of parallel G4, with each block exclusively containing guanines from either the TBA sequence or the Block2 sequence. The two blocks were connected by a TT linker.
The capping bases were found to be superimposed well, while the protruding bases were not (Supplementary Figure  S9B ). This is not surprising as the electron density Statistics for the highest-resolution shell (1. 9-1. 8 Å) are shown in parentheses. did not fit convincingly around these protruding thymine bases. In addition, our NMR data did not show any interresidue NOE cross-peaks for T4 and T13, while T7 had cross-peaks with only G8. Both the techniques suggested that these three thymine residues were disordered. Overall, the high degree of agreement between the crystal structure of TBA-T-Block2 and the solution NMR structure of TBA-TT-Block2 indicated that the two sequences folded into similar structures regardless of the linker length, and thus confirmed the formation of a structure with adjacent right-and left-handed G-quadruplexes.
Single-nucleotide loops are preferred or required for the lefthanded G-quadruplex formation The solved crystal structure of Z-G4 (PDB ID: 4U5M) (36) was shown to adopt a left-handed G4 despite the original right-handed conformation of the isolated Block1 sequence 5 -d(TGGTGGTGGTGGTT)-3 (37) (Supplementary Figure  S11A ). In both Z-G4 and our TBA-T-Block2 sequences, Block2 motifs were shown to drive a different folding topology on the attached sequences (Block1 and TBA, respectively). However, the Block1 sequence was converted into a parallel left-handed structure, while the TBA sequence was changed into a parallel right-handed structure (Supplementary Figure  S11B ). Examining the differences between the attached sequences, we noticed that while Block1 consisted of three single-T loops, TBA comprised of relatively longer loops (two TT loops and one TGT loop).
High-throughput sequencing and bioinformatics Amplicon sequencing targeting the V6eV8 region of the 16S ribosomal RNA (rRNA) gene was performed on a Miseq sequencer at the Institut de Biologie Int egrative et des Syst emes (Universit e Laval, Qu ebec, QC, Canada). Two replicates for each temperature condition were used for the sequencing step. Raw demultiplexed paired-end reads of each replicate were deposited in the GenBank database under the accession number SRP140914 (first replicate, 3,285,298 raw demultiplexed reads) and SRP150623 (second replicate, 3,169,154 raw demultiplexed reads). The computations of the reads of each replicate were processed separately, as previously described  (Chamberland et al. , 2017a) , with the modifications described next. Computations were done with the pipeline FROGS from the Galaxy portal of the INRA MIGALE Bioinformatics platform (Jouy-en-Josas Cedex, France; Escudi e et al.
, 2017;  Goecks et al. , 2010). Following reads preprocessing (quality filter, read trimming and read assembly), contiged reads were clustered with the Swarm clustering method using the denoising clustering step and the suggested aggregation distance of 3 (Mah e, Rognes, Quince, de Vargas, & Dunthorn, 2014). A first chimera filter was performed with VSEARCH  (Rognes, Flouri, Nichols, Quince, & Mah e, 2016). Operational taxonomic units (OTU) with abundance lower than 0. 005% were removed  (Bokulich et al. , 2013). The SILVA database (release 132, December 13, 2017) was used to perform the OTU affiliations. Each OTU was manually inspected a second time to remove undetected chimeras. The final OTU tables obtained for each replicate were finally merged by taking the sum of the absolute abundance of each taxon.
Statistical analysis As mentioned, the experimental design was repeated three times for each temperature. A one-way analysis of variance (ANOVA) of the number of 16S rRNA gene copies variable was performed with RStudio (v. 1. 0. 136) using the package agricolae (v1. 2-8). The analysis was performed separately for membrane and milk samples. The number of gene copies among samples were considered significantly different with a p-value smaller than 0. 05 (Fisher's least significant difference test).
Acknowledgements This work was supported by the  NSERC-Novalait Industrial Research Chair on Process Efficiency in Dairy Technology  (grant number  IRCPJ 46130-12  to  Yves Pouliot ) and the  Fonds de recherche du Qu ebec e Nature  et technologies through a  doctoral research scholarship  (grant number  199094 ). Eric Dugat-Bony was supported by the  AgreenSkills þ fellowship  programme which has received funding from the  EU's Seventh Framework Programme  (grant number  FP7-609398 , AgreenSkills þ contract). The authors are thankful to  Barb Conway  for editing this manuscript. We are also grateful to the  INRA MIGALE bioinformatics platform  (http://migale. jouy. inra. fr)for providing computational resources.
Statistical analysis The trend of proportion of patients with DST was analyzed using the chi-square trend test. The trend of mean intervals between diagnosis and TMTC enrollment was analyzed using linear regression models. Poisson regression models were constructed to analyze the trend of MDR-TB incidence and prevalence, and the trend of chronic infectious TB prevalence. We analyzed the trend of proportion of MDR-TB among all TB cases from 2010 to 2016, because the proportion of patients with DST was relatively low before 2010. The trends of proportion of MDR-TB among new and recurrent TB cases were analyzed using the chi-square trend test. All analyses were conducted using SAS software version 9. 3 (SAS Institute, Cary, North Carolina).
As existing chronic infectious cases died over time, and a small fraction of existing chronic infectious cases were cured by bedaquiline and other repurposed drugs, we managed to drastically reduce the prevalence of chronic infectious TB cases by 70% from 2007 to 2016. Consequently, transmission of MDR-TB was averted, resulting in the reduction of the proportion of MDR-TB among new TB cases from 1. 4% in 2010 to 1. 0% in 2016. Our study has strengths. First, it is a population-based study that covers the total population in Taiwan. Second, PMDT in Taiwan has been in consistent operation with good collaboration between partners for 10 years, providing us with quality data for this analysis. This study has some limitations. First, we used notification data to assess the incidence of MDR-TB, but there might be gap between incidence and notification if under diagnosis and under reporting of TB is substantial.
Statistical analysis Statistical evaluation determined that the number of rats required for in vivo experiments to show a 30% increase in SV by landiolol with a power and an alpha risk of 80% and 5%, respectively, was six per group. From the 6-8 animals per group tested in vivo, 5-6 hearts per group were selected as described in the above experimental protocol and used for gene expression quantification. No statistical evaluation was a priori performed but five biological replicates per group are empirically required for common designs  [30]. In total, 32 raw data files (five arrays for the sham, five arrays for the CLP and six arrays for the CLP plus landiolol groups, for each sex) were obtained using the Agilent Feature Extraction Software. The raw intensity data were exported as a single Excel spread sheet, and the raw data was converted in log2.
Quantile normalisation was then applied to correct for global intensity and dispersion, and an 80% filtering was used to keep only genes expressed over the background noise. This procedure generated 38,223 probes in males and 37,605 probes in females. All the microarray data files are accessible at NCBI's Gene Expression Omnibus website (accession number: GSE125042). To detect significant variation in gene expression between groups (CLP group vs sham group and CLP plus landiolol group vs CLP group), the significance analysis of microarrays (SAM) method was used, with 10,000 permutations applied with a false discovery rate (FDR) of 1% or 5%. Hierarchical clustering of differentially expressed genes (DEGs) was achieved using the TM4 Microarray Software Suite V4. 9 (http://mev. tm4. org) and average linkage clustering metrics.
Functional annotations For biological interpretation of the gene expression data, enriched functional annotations for the up-and down-regulated genes were identified using the Database for Annotation, Visualization and Integrated Discovery (DAVID) Bioinformatics Resources 6. 7 (https://david. ncifcrf. gov). Biological processes, cellular components and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were considered significantly enriched when P-Benjamini < 0. 05. The KEGG pathways (http://www. genome. jp/kegg/) were also used when no significant biological processes were found in DAVID. Cytoscape was used to design the gene network of CLP genes whose expression was reversed after landiolol administration (http://www. cytoscape. org).
The lists of DEGs are shown in the Additional file 1. To assess CLP-related functional annotations, we used biological processes, gene ontology terms and KEGG pathways using the DAVID database for the 2850 and the 1267 DEGs from males and females, respectively. For up-regulated genes, the most significant biological processes were associated with inflammatory and immune responses, apoptosis, metabolism, oxidative stress, muscle cell proliferation, protein kinase activity and the development of primary sexual features. For down-regulated genes, the biological processes were related to mitochondrion, muscular cell organisation (organelles, myocyte membrane and contractile proteins), muscle contraction, blood circulation, ionic transport and phosphoinositide-3-kinase/AKT (PI3K/AKT) signalling pathway.
c, d A gene ontology analysis realised with the DAVID Database is reported on graphs in which the most significant biological process (BP)-GO terms for up-and down-regulated genes are indicated for CLP vs sham groups (c) and for CLP plus landiolol vs CLP groups (b). For all the processes, the number of genes deregulated in males is much greater than in females. Note the total absence of significant biological processes for females after landiolol infusion in (d). (*) indicates over-expressed biological processes during CLP that were reversed by landiolol. ( §) indicates underexpressed biological processes during CLP that were reversed by landiolol. (#) indicates under-expressed biological processes related to cardiac activity and cardiomyocyte function that were affected during CLP and were not restored by landiolol.
3a  and Additional file 3: Table  S2 ). In females, only the AMP-activated protein kinase (AMPK) signalling pathway was found associated with three significant DEGs (Fig. 3b ). a b Fig. 2  Biological processes associated with up-regulated genes after cecal ligation and puncture and backregulated by landiolol infusion. a Venn diagram associated with the 1259 up-regulated genes in CLP group and the 418 down-regulated genes in CLP plus landiolol group in males. The 226 common genes represent regulated genes with a characteristic V form, up-regulated in sepsis and back-regulated by landiolol infusion. From these 226 common genes, a gene ontology analysis with the DAVID Database revealed significant biological processes (P-Benjamini < 0. 05). A gene network diagram was performed using Cytoscape integrating the 226 genes (light grey circles) with their associated biological processes (dark grey rectangles).
Acknowledgments Transcriptomic experiments were performed at the  TGML Platform , supported by grants from  INSERM ,  GIS IBiSA, Aix-Marseille Univ  and  ANR-10-INBS-0009-10. We are grateful to  P. Rihet ,  L. Spinelli  and  Y. Labiad  for discussions on transcriptomic analysis and  A. Bergon  for help with computing tools.
IRS data reduction Spectra of comet 8P/Tuttle acquired with the IRS instrument were initially processed and calibrated with the Spitzer Science Center's IRS pipeline (version S17. 0. 4). We subtracted a shadow observation from each target observation to remove the sky background. Some residual background flux still remained in the 2D spectral images. Therefore, a second subtraction was performed using median-combined sky frames taken contemporaneously with the comet. This removes any zodiacal light or instrument background not fully accounted for in the shadow observations. Bad pixels were identified and replaced via nearest-neighbor interpolation, or ignored altogether. We extracted spectra from the 2D images using the Spitzer Science Center's SPICE software 3. Our synthetic apertures, centered on the peak of the source, used the default point source aperture widths, which vary with λ/λ 0 : 4.
MIPS data reduction The images acquired with MIPS were processed with the Spitzer Science Center's pipeline (version S18. 0. 2), producing individual basic calibrated data (BCD) frames. We subtracted a shadow observation from each target observation to remove the sky background. The BCD images were subsequently mosaicked in the rest frame of the comet with the MOPEX software (version 16. 3. 7). Bad pixels, that is those permanently damaged, or affected by cosmic rays, were ignored during the mosaicking step. Figure  1  shows an example of a calibrated image at 24 µm and 70 µm. The coma, dust tail and first Airy ring are visible in the 24 µm image, indicating a high nucleus to coma ratio in the central pixel. The extraction of the nucleus signal was performed using our standard method of fitting a parametric model of the expected surface brightness to the observed images, as implemented for instance to MIPS observation of comet 67P/Churyumov-Gerasimenko by  Lamy et al.