dataesr/scientific-paragraphs-categorization huggingface dataset:
Two rate laws were tested, a first order proposed by  Bessinger et al. (2012)  and a second law based on the work by  Heyes et al. (2006)  (Table  2 ) and which rate corresponds to a balance between both methylation and demethylation rates. The possible formation of complexes at the ferrihydrite surface is implemented, using capacity of ferrihydrite, using the  Dzombak and Morel (1990)  model and database. Numerical modelling uses PhreeqC-2 code  (Parkhurst and Appelo, 1999)  and the Thermoddem database  (Blanc et al. , 2012). The conceptual model is based on 1D-cartesian geometry, as displayed in Figure  4. A tracer test has been successfully simulated to verify the hydrodynamic set of parameters used.
Such increase happens during a period when calcite precipitates. It also corresponds to the precipitation of Mackinawite, observed in the experiments by  Hellal et al. (2015) , using Raman spectroscopy. From the reaction displayed in Table  2 , mackinawite precipitation happens to consumes protons which increases pH and can lead induce the precipitation of carbonates. For dissolved mercury (Figure  5 ), the total concentrations were correctly predicted. Methylmercury concentrations analyzed were somewhat bracketed by the calculation performed with the model proposed by  Bessinger et al. (2012)  and  Heyes et al. (2006)  (Model 1 and Model 2 in Figure  5 , and  from the thermodynamic dataset. In addition, it enhances possible connections between inorganic and organic dissolved carbon forms, from the point of view of methylation processes.
Stimulus generation and AEP recordings. A Tucker-Davies Technologies (TDT, Alachua, FL, USA) AEP workstation was used to generate sound stimuli and record AEP waveforms. TDT SigGen software was used to create sound stimuli with an RP2. 1 enhanced real-time processor, a PA5 programmable attenuator to control sound level, and a power amplifier before being sent to and emitted by the underwater speaker. Sound stimuli were tone bursts of 50 ms in duration gated with a Hanning window. The phase of the tone was alternated between presentations to minimize electrical artefacts from the recordings. Fifteen frequencies were presented to each fish: 50, 150, 300, 600, 900, 1200, 1500, 1800, 2100, 2400, 2700, 3000, 3300, 3600 and 4000 Hz. At each frequency, sound levels were presented up to 164 dB re 1 µPa and were attenuated in 6 dB steps until a threshold level was determined.
Evoked potentials recorded by the electrode were amplified (TDT HS4-DB4 amplifier, 10,000 gain), connected to an RP2. 1 enhanced real-time processor, routed into the computer and averaged by BioSig software. At each frequency and for each sound level, the signal was presented 500 times. Sound levels of the acoustic stimuli were calibrated with a Brüel and Kjaer 8101 hydrophone (Naerum, Denmark; sensitivity -164 dB re 1 V/µPa; bandwidth 0. 1 Hz to 200 kHz) placed in the steel tube at the previous position of the fish's head. The hydrophone was connected to a calibrated Brüel and Kjaer 2610 amplifier that gave the absolute pressure level of sound stimuli. Evoked responses were averaged and power spectra were calculated using a 4096-point Fast Fourier Transform (FFT). The spectra were analysed for the presence of peaks at twice the stimulus frequency with heights at least 3 dB above the background level.
Acknowledgements We thank  Zora Gabsi ,  Philippe Keith , and  Patrice Pruvost  ( MNHN, CNRS UMR 7208 ) for assistance and access to MNHN specimen loans. We are grateful to  Miguel Garcia Sanz  and  Patricia Wils  from the  AST-RX platform at MNHN  ( CNRS UMS 2700 ) for μCT scanning and training in Avizo. This study was supported by grants from  F. R. S. -FNRS  (no. T. 0101. 15 ). K. B. was funded by a  Marie-Skłodowska Curie fellowship  ( EU  project  625039 -EvoMorphASIS ). G. M. was funded by the  Fonds pour la formation à la Recherche dans l'Industrie et l' Agriculture (F. R. S. -FNRS ).
The recent European guidelines describe chemotherapy responses as being ''of short duration with a median overall survival rate of 9 months and high toxicity in elderly patients''  [10]. Avelumab is a human monoclonal antibody that binds and inhibits programmed death ligand 1. The use of immunotherapy in MCC is new and provides a distinct mechanism of action and adverse event profile compared with cytotoxic chemotherapy, which has been the standard treatment in these patients. The safety and efficacy of this immunotherapy was assessed in a phase 2 trial (JAVELIN Merkel 200; NCT02155647) in 88 patients with stage IV chemotherapy-refractory MCC and was associated with durable responses in 32% of patients  [11]. In addition, pembrolizumab, a programmed cell death receptor 1 (PD-1)-targeted monoclonal antibody, has also shown promise in patients with metastatic MCC treated in the first-line setting  [12].
These developments have supported immunotherapy as a new standard of care for patients with advanced and metastatic MCC. While the availability of new therapeutic options is welcome, there is a paucity of data available regarding the impact of MCC disease and its management on patients' health-related quality of life. Therefore, qualitative research was undertaken to provide a comprehensive overview of the impact of MCC and its management on patients' lives prior to diagnosis, at diagnosis, and after diagnosis, and to develop a disease model of adults with metastatic MCC. Qualitative exploratory interviews were conducted with the patients enrolled in the JAVELIN Merkel 200 clinical trial, at baseline before the start of the study treatment. In this manuscript, we report the methodology and findings of this qualitative research.
Study Design The single-arm, open-label, multicentre, international, phase 2 JAVELIN Merkel 200 trial was conducted to evaluate the efficacy and safety of avelumab in patients with stage IV, chemotherapy-refractory, histologically confirmed MCC (aged C 18 years), i. e. metastatic patients who had failed at least one line of chemotherapy (NCT02155647). Details of the design of the trial, including efficacy and safety endpoints, have been reported elsewhere  [11]. Upon recruitment, patients were invited to participate in optional qualitative interviews in all countries (Australia, Austria, Canada, France, Germany, Italy, Spain, Switzerland, and the USA), except Japan where interviews were viewed as culturally insensitive. Patients agreeing to participate were interviewed during the screening period, before first administration of the study treatment (baseline patient interviews).
Qualitative Analysis of Patient Interviews Interview transcripts were analysed by trained and experienced qualitative researchers (JL, IG), using the ATLAS. ti qualitative software package  [15, 16]  and a thematic analysis  [17]. JL, who is a male researcher holding a PhD in oncology, analysed all interviews; IG, a female researcher with many years of experience in qualitative research, analysed separately about two thirds of the transcripts (n = 11). Both researchers discussed their analyses and solved any conflicting points, before aggregating the results and drawing conclusions. The analysis consisted of the attribution of tags (a code made of one to two words) summarising the idea being conveyed to a word, a sentence, or a paragraph of each of the transcripts. A first specific tag was applied related to the time of reference (e.
Eligibility criteria and study design This was a retrospective study conducted on behalf of the Société Francophone de Greffe de Moelle et de Thérapie Cellulaire (SFGM TC), including all adults (≥18 years old) who received a clofarabine/busulfan based RIC allo-SCT for myeloid malignancies (AML, MDS, myeloproliferative syndrome (MPS)) and reported within the SFGM-TC registry. Data were obtained through PROMISE, an internet-based system shared by all European transplantation centers. All patients gave informed consent for collection of their personal data in this data base.
Funding This project has received funding from the  ECSEL JU  under grant agreement no. 692482. This JU receives support from the  European Union 's  H2020 research and innovation programme and France ,  Netherlands ,  Denmark, Belgium, Germany ,  Czech Republic , and  Spain. The authors are also grateful for the supports from  Region Centre  ( MEPS  project  2015-2018 ) and  National Research Agency  ( ANR-14-CE08-0010-01 ).
clinical Data collection Clinical data recorded at baseline were gender, age, number of daily new blisters (determined over a 3-day period), and BPDAI. BPDAI was calculated according to the International Pemphigoid Committee recommendations  (9). At baseline, BPDAI was recorded. The total BPDAI computes two scores: total BPDAI activity and total BPDAI damage. The total BPDAI activity score is the arithmetic sum of the three subcomponents-cutaneous blisters/erosions, cutaneous urticaria/erythema, and mucosal blisters/erosions. The total BPDAI damage score is the arithmetic sum of the items rated regionally for damage caused by more permanent features such as post-inflammatory hyperpigmentation, scarring, and other. BPDAI also takes into account lesion number and size thresholds and skin lesions are rated based on the regions affected.
Another weakness is the lack of investigations regarding biopsy specimens or BFs from oral mucous membrane for pathophysiological purpose. Unfortunately, recent intact oral blisters were rare and too transient for an effective, systematic sampling. To avoid biases, our present results were based on clinical or biological data which could systematically be collected in all consecutive patients. Although we observed that mucosal involvement also occurred in patients with mild or moderate disease, we here showed that mucosal involvement was more frequent in patients with severe BP according to the BPDAI score. Actually, in those severe BP patients, mucosal involvement could represent a severity criterion but not a clinical atypia. Considering all elements discussed above, further investigations should help defining the pathophysiological particularities of severe BP patients with autoantibodies against both the BP180 N-and C-terminal of the ectodomain was associated with the presence of mucosal lesions  (44).
The above data provide broad validation of the microarray datasets and suggest that they are appropriate for a search for uniquely enriched transcripts in E8. 5 NMPs. Nevertheless, no uniquely upregulated genes were detected in the CLE. Only four genes were upregulated specifically in the NSB. In situ hybridisation for those for which unique probes could be designed, Bhmt2 and Ccno, confirmed their specific localisation in the NSB (Fig. 2B ). However, their expression was confined to the ventral layer corresponding to the crown of the node, rather than to the NMP-containing dorsal layer. The levels of known NMP markers T and Sox2 correlated well with protein levels measured by immunofluorescence, underlining the accuracy of dissection  (Wymeersch et al. , 2016)  (Fig. 2D ). Specifically, levels of Sox2 correlated with neural fate in the sample, whereas levels of T reflected its high expression in the notochord and posterior streak, as well as anterior streak midline  (Wymeersch et al.
However, the enrichment of individual pathway members respected these domains. Moreover, the Nodal response genes Lefty1 and Lefty2, and the Hedgehog target Ptch1 were upregulated in the RN-NSB domain, whereas Fgf and Wnt target genes (Dusp6 and Axin2 respectively) were upregulated in NSB-CLE-St1. Bmp targets Id1, Id2 and Id3 were upregulated in St5, indicating that these signalling pathways have localised activation patterns (Fig. 3B ). To determine whether these patterns were specific to signalling pathways known to operate in primitive streak morphogenesis, or reflected more global patterns of gene expression, we analysed all DEGs at E8. 5 via hierarchical clustering and explored their function in the STRING online database  (Franceschini et al. , 2013)  (Fig. S3A ). This expanded analysis also grouped genes into the three major categories identified above, indicating that these domains contain cells with broadly similar transcriptomes.
5 and E10. 5 (n genes =160 and 42). A group of 139 genes peaked at E10. 5 and overlapped with those upregulated between E8. 5 and E10. 5. Further groups of 46, 43 and 98 genes showed variations of this pattern with slightly broader peaks, whereas 37 genes peaked at E13. 5. The lack of any other patterns indicates that changes between E8. 5 and E10. 5 constitute the major transcriptional diversity in NMPs over time. A further set of 46 members of transcription factor families or signalling pathways (Hox, Fox, Tbx, Pou, Wnt, Fgf, Notch and RA) was identified by correlation with the pattern of a typical profile for the 139 genes peaking at E10. 5, i. e. that of Wnt5a (Fig. S6B ; Table  S6 ). Combining these datasets generated a list of 313 genes upregulated between E8. 5 and E10. 5, the expression of which declined thereafter (Fig.
, 2015)  but information on the exact time of activation of these genes in mouse embryos is incomplete. We therefore examined our whole microarray dataset for patterns and timing of Hox activation and further upregulation. Hox genes can be broadly classified into anterior ( paralogous groups, PG1-3), central (PG4-8) and posterior (PG9-13) subgroups (reviewed by  Young and Deschamps, 2009) , with PG13 (here referred to as 'terminal') proposed to precipitate the decision to stop axis elongation  (Young et al. , 2009). After filtering out probes that did not show activation above background (Fig. S9I ), genes were grouped according to the above criteria (Fig. 6A ). PG1-3 genes were highly expressed in the E7. 5 headfold stage primitive streak. Their expression declined gradually after E9. 5 (Fig.
Microarray analysis RNA was isolated using the RNeasy Micro Kit (Qiagen) and labelled and amplified using the Illumina TotalPrep RNA Amplification Kit (Life Technologies). The sample concentrations and quality were determined using a 2100 bioanalyzer (Agilent). Samples were loaded on six MouseWG-6 v2. 0 Expression BeadChip arrays (Illumina). Data normalisation was performed using the lumi package in the R statistical environment  (Du et al. , 2008). Pre-processing steps consisted of a background adjustment, followed by Variance-Stabilizing Transformation (VST) and Robust Spline Normalization (RSN). A final quality control step was carried out to detect outliers, and probes that were not expressed in any samples were filtered (23,569 out of 45,281 probes; detection P-value<0. 01). ComBat analysis  (Chen et al.
, 2011)  was used to correct for any batch effects. DEGs were identified using the limma package ( parameters: BH with fold-change ≥1. 5 and FDR ≤0. 05;  Smyth, 2004). Marker expression in individual microdissected pieces has been shown previously  (Cambray and Wilson, 2007; Wymeersch et al. , 2016)  and is validated by qRT-PCR and in situ hybridisation here (Fig. S1 ; Fig. S2 ). Hierarchical clustering was performed using the Morpheus visualisation tool (software. broadinstitute. org/ morpheus). To assign genes of interest to a specific signalling pathway or cellular process, we used the Kyoto Encyclopedia of Genes and Genomes  (Kanehisa et al. , 2016)  and the STRING database  (Franceschini et al. , 2013).
Image analysis Whole-mount embryo images were taken on a Nikon AZ100 (Nikon) or Leica M165 FC microscope (Leica). A wide-field Olympus BX61 or Zeiss Observer microscope with fluorescence optics were used to capture images of immunostained cryosections. Confocal imaging was acquired on a Leica TCS SP8 platform (Leica). Image processing was carried out using Adobe Photoshop (Adobe Systems) and ImageJ software  (Schneider et al. , 2012).
Acknowledgements We thank  Sally Lowell ,  Anestis Tsakiridis ,  Guillaume Blin ,  James Briscoe ,  Alfonso Martinez-Arias ,  Donal O'Carroll  and all V. W. lab members for critical reading of the manuscript;  Carol Manson ,  John Agnew  and  Laura Borthwick  for help with animal maintenance;  Ron Wilkie  for technical assistance; and  Anne Wiblin  and Abcam for advice and reagents.
2014). At acceptably concentrations for humans, tamoxifen combined with fluconazole decreased brain fungal burden, and has demonstrated to inhibit the growth of C. neoformans within macrophages, which are not accessible by classical antifungal drugs. It has also the benefit to have a good oral bioavailability. Therefore, an open-label, phase II, randomised trial ("A randomised trial of tamoxifen combined with amphotericin B and fluconazole for cryptococcal meningitis", NCT03112031) will enrol 50 patients in Vietnam, comparing EFA according to the strategy between (amphotericin B plus fluconazole ± tamoxifen during the first two weeks).
Moreover, rivers may transport B. pseudomallei from sources in the watershed and thereby indicate the presence of B. pseudomallei in the catchment and act as carriers for its environmental dispersal. The aims of this pilot study were to investigate (i) the geographical distribution of B. pseudomallei in Laos and (ii) whether rivers are potential reservoirs and/or carriers for B. pseudomallei. For this purpose, we used two independent methods, conventional culture and PCR after enrichment, to detect B. pseudomallei in river water and, for the first time, in streambed sediments, and assessed the distribution data in an environmental context to explain spatiotemporal variations.
Acknowledgements We are grateful to the  Lao Department of Agricultural Land Management  and  Dr. B. Bounxouei  for facilitating this study at the  Mahosot Hospital  and in the field, to  Dr. M. Vongsouvath  and the staff of the  Mahosot Hospital Microbiology Laboratory ,  Dr. S. Dittrich ,  A. Rachlin ,  Dr. P. Nawtaisong ,  A. Chanthongthip ,  Dr. E. Rochelle-Newall ,  Prof M. Lehmann ,  Dr H. Niemann ,  Dr. T. Kuhn ,  J. Kobler-Waldis , and  R. Strunk  for their help with laboratory work, technical inputs or logistical support, to  V. Roth  and the  Centre for Development and Environment  for providing map shapefiles, and to the  Nam Theun 2 Power Company (NTPC)  for providing logistical support and access to their site. This study was funded by the  US Defence Threat Reduction Agency Cooperative Biological Engagement Programme  (contract  HDTRA-16-C-0017 ) (main funding), the  Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit  funded by the  Wellcome Trust of Great Britain  (Grant number  089275/H/09/Z ), the  French National Research Agency  ( TecItEasy  project,  ANR-13-AGRO-0007 ), and the  Institut de Recherche pour le Développement.
It has been suggested that anti-bubble agents, such as simethicone, given in a liquid form (80 mg to 600 mg), 20 minutes before capsule ingestion, may enhance mucosal visualization in SB-CE. However, these agents do not significantly increase the procedure's diagnostic yield  [4, 8 -13]. Moreover, validated methods to assess the amount of bubbles in CE recordings are lacking, which implies that data on anti-bubble agents are from low-quality evidence. Studies on SB cleaning scores suggest that grading scales should focus on quantitative rather than qualitative criteria to achieve better reproducibility. Therefore, we believe that an objective, reproducible score assessing the amount of bubbles in SB-CE is needed for both clinical practice and research purposes  [14]. The aim of this study was to develop and validate a computed method, which would allow assessment of the abundance of bubbles covering the surface of still images.
Image databases The first dataset was created using 200 SB-CE separate, nonconsecutive, and non-clustered still frames exported from 45 SB-CE video sequences. The dataset was divided into five groups consisting of 40 still frames each. Each group was cre-ated based on the surface of mucosa (in percentage) that could not properly be examined because it was covered with bubbles. This first analysis was performed by OP. Group A comprised still frames with less than 2 % bubbles, group B comprised still frames with 2 % to 10 % bubbles, group C comprised still frames with 10 % to 25 % bubbles, group D comprised still frames with 25 % to 50 % bubbles, and group E comprised still frames with 50 % to 100 % bubbles. ▶ Fig. 1  and ▶ Fig. 2  show the variety of bubble abundance on different still frames.
Computed algorithms Four different computed algorithms, recognizing circular patterns, were tested in terms of their ability to adequately categorize each still frame based on the amount of bubbles, lower or higher than 10 % (i. e. in the "scarce in bubbles" or "abundant in bubbles" groups) using a similar binary classification. These tests were performed using the MATLAB software (MathWorks, Natick, Massachusetts, United States). The four algorithms were divided into two groups, depending on the type of results generated. The first group included two feature-based methods, since the output of each method ("scarce in bubbles" or "abundant in bubbles") depended on a computed threshold, based on a particular characteristic of the image. The second group included two methods allowing quantification of the actual surface of the still frame presenting with bubbles.
Images a, b and c represent still frames with less than 2 % of bubbles. Images d, e and f represent still frames with 2 to 10 % of bubbles. of bubbles), comparable to the threshold used during the expert analysis. The first dataset (200 images) was analyzed, using the binary classification ("scarce in bubbles" or "abundant in bubbles" groups) produced by expert readers as reference. Calculation time, receiver operating characteristic (ROC) curve, area under ROC curve (AUROCC), as well as sensitivity (Se), specificity (Sp), ▶ Fig. 2  Set of still frames categorized in the "abundant in bubbles" group, according to expert analysis. Images a, b and c represent still frames with 10 to 25 % of bubbles. Images D, E and F represent still frames with 25 to 50 % of bubbles. Images g, h and i represent still frames with 50 to 100 % of bubbles.
Validation step Algorithms with the best operating point (i. e. , the highest sum of Se and Sp) were selected for further validation. Se, Sp, NPV and PPV values were calculated for the selected algorithms applied on the second dataset of 200 still frames (for cross-validation), using the binary classification ("scarce in bubbles" or "abundant in bubbles" groups) produced by two different expert readers (MC and INL) as reference. The primary endpoints for validation were κ = 1, Se ≥ 90 %, and Sp ≥ 85 %. The secondary endpoint was the calculation time by frame < 1 second.
Development step Concerning the first dataset, intraobserver correlation coefficients were κ = 0. 92 for XD and κ = 0. 97 for CF. The interobserver correlation coefficient was κ = 0. 96 for both expert analyses. The first analysis presented a discrepancy in 13 still frames (6. 5 %). Eventually, 90 still frames (45 %) were categorized as "scarce in bubbles" and 110 still frames (55 %) as "abundant in bubbles". The diagnostic capabilities of all four algorithms are provided in ▶ Table  1. All algorithms achieved a 1. 00 intraobserver correlation κ coefficient and a sensitivity of 100 %, but specificity varied substantially. The SURF detector strategy had the highest operating point yielding the following: Se of  94  ▶ Fig. 3  shows illustrations of the obtained outputs for algorithms 3 and 4 (whereas no visual illustration can be given for threshold-based algorithms 1 and 2).
Validation step In the second dataset, intraobserver correlation coefficients were κ = 0. 96 for both MC and INL. The interobserver correlation coefficient was κ = 0. 89 for the first analysis, and κ = 0. 88 for the second analysis. The first analysis presented a discrepancy in 68 frames (34 %). Eventually, 96 frames (48 %) were ca-▶ Table  1  Sensitivity, specificity, NPV, PPV, and AUROCC of the four algorithms used to evaluate bubble abundance in small bowel capsule endos- copy still frames. The calculation time by frame was significantly lower than that of the SURF detector strategy (0. 037 ± 0. 005 seconds [P < 10 -5 ]).