dataesr/scientific-paragraphs-categorization huggingface dataset:
, Santa Clara, CA, USA) according to the manufacturer's instructions. The presence of the intended mutation was verified by automated DNA sequencing (Eurofins Genomics, Germany). Thermostability assay. Thermostability of purified recombinant P-Etx-D250A was assessed by mixing purified protein (0. 25 mg ml -1 ) with 240× SYPRO Orange protein gel stain. Fluorescence was monitored using a QuantStudio™ 6 Real-Time PCR System (Applied Biosystems, USA) with a 1% thermal gradient from 25 °C to 99 °C. The fluorescence data obtained was analysed using the Protein Thermal Shift Software (Applied Biosystems, USA) to calculate the melting temperature (T m ) using the Boltzmann method. Cell culture. Super Dome (ATCC® CRL-2286 ™ ; American Type Culture Collection (ATCC), USA) cells, a canine epithelial-like cell line established by cloning from the MDCK (ATCC® CCL-34 ™ ) cell line, were routinely cultured in Dulbecco's modified Eagle's medium/Ham's F12 medium (DMEM/F12, HEPES; Life Technologies) with 2.
The solubilization yields for each detergent were determined by calculating the % of Etx pore in the supernatant relative to its amount in the total protein sample using Image Studio ver 5. 2 software (LI-COR Biosciences, Lincoln, USA). Epsilon pore purification. For DDM-extracted samples, solubilized Etx oligomers were bound to Ni-NTA resin (Qiagen), washed with 20 volumes of DPBS containing 20 mM imidazole and 0. 02% (w/v) DDM, transferred to a Bio-Rad gravityflow column, washed again with 20 volumes of DPBS containing 20 mM imidazole and 0. 02% (w/v) DDM, and eluted in three volumes of DPBS containing 200 mM imidazole and 0. 02% (w/v) DDM. Binding and oligomerization. Super Dome cells were grown to confluence in 6-well plates (1. 2 × 10 6 cells per well), and after washing cells three times with DPBS to remove residual trypsin, each well was incubated with 2 ml prewarmed DMEM-F12 medium containing trypsin-activated recombinant Etx wild-type, Etx-D250A or Etx-H162A (391 ng ml -1 , equivalent to 5× CT 50 dose of wild-type Etx) at 37 °C for 1 h to allow binding and/or oligomerization.
Antibodies were diluted in PBS containing 0. 1% Tween-20 and 3% skim milk. Immuno-reactive bands were detected using the Odyssey CLx infrared imaging system (LI-COR Biosciences, Lincoln, USA). Quantitative analyses were performed using the Image Studio ver 5. 2 software and the Housekeeping Protein Normalization Protocol (LI-COR Biosciences, Lincoln, USA). The oligomer yield for each Etx variant was determined by calculating the percentage of fluorescence intensity relative to wild-type toxin. Negative stain EM. Purified recombinant P-Etx variants were trypsin activated as described above. After activation, samples were diluted to 0. 02 mg ml -1 and 3 μl was added to freshly glow-discharged carbon-coated grids for 60 s before staining with 20 μl of 2% (w/v) aqueous uranyl acetate. Grids were then imaged on a Philips CM200 FEG transmission electron microscope operating at an accelerating voltage of 200 kV.
Images were recorded at a calibrated pixel size of 2 Å on a TVIPS F224HD CCD camera. Specimen preparation and data collection. Etx eluate fraction 4 (∼0. 04 mg ml -1 ) was diluted 3-fold in elution buffer (DPBS containing 20 mM imidazole and 0. 02% (w/v) DDM) and deposited on Quantifoil R1. 2/1. 3 grids overlaid with graphene oxide, as described in ref. 20. Grids were then blotted and plunge frozen using a custom-made device and stored in LN2 until further use. Data were collected on an FEI Titan Krios operating at an accelerating voltage of 300 kV. All datasets were collected on an FEI Falcon 3EC direct electron detector at a nominal magnification of ×75K (calibrated pixel size of 1. 07 Å) and a dose rate of 0. 6e-per pixel per second in counting mode over 60 s and 75 fractions. Conventionally defocused and phase plate datasets were collected using the EPU software (Thermo Fisher Scientific).
In brief, grid squares and suitable holes were selected and microscope alignments were performed. Just prior to data collection, the phase plate was inserted and the un-scattered beam was made parallel by observing the Ronchigram in the back focal plane of the objective lens over an empty specimen area. Condenser astigmatism was corrected by reducing the smearing of the Ronchigram near the blow-up point. Due to the extremely low screen current used (~0. 014 nA), the 150 μm C2 aperture was used to aid in this process and then switched back to the 50 μm aperture. Coma and astigmatism were corrected using AutoCTF. Defocused data were collected by defocusing between -2 and -3. 5 μm every 15 μm, and phase plate data between -0. 3 and -0. 8 μm with focusing at every hole. Image processing. All datasets were processed in Relion-3  52.
Micrographs were first corrected for large movements using MotionCorr2  53  and a 4 × 4 patch with no grouping. CTF parameters were estimated using GTCF  54. Autopicking was performed in Relion after creating references from manually picked particles. The processing procedure is summarized in Supplementary Fig. 4. The resolution was calculated using Gold-Standard 0. 143 criterion, resulting in a 4. 6 Å map for the defocused dataset and 3. 2 Å for the phase plate dataset. The variation in resolution in the map was calculated using the Relion local resolution implementation. Box sizes of 220 pixels were used for both the defocused and phase plate datasets. To ensure that high-resolution information was not lost by the high defocus values used for the former dataset, particles were re-extracted in 400 pixel boxes and subjected to 3D refinement.
No increase in resolution was observed for the larger box size particles. B-factor plots were calculated using the bfactor_plot. py scripts provided with Relion. Model building and refinement. A model was built into the 3. 2 Å map by initially docking the RBD of wild-type Etx crystal structure (PDB: 1UYJ) and then extending this using Coot. Refinement of the atomic coordinates was performed using Phenix  55  real space refine and re-iterating the model building-refinement procedure several times. Statistics. Data were analysed using the Prism v7 software (GraphPad Software Inc. , La Jolla, CA, USA). Data are expressed as the mean value ± SEM. Reporting summary. Further information on research design is available in the Nature Research Reporting Summary linked to this article.
Acknowledgements We thank  Professor Nicholas Harmer  and  Alice Cross ,  University of Exeter, UK  for assistance with the thermostability assay. We also wish to thank  Dr. Shaoxia Chen ,  Dr. Giuseppe Cannone ,  Dr. Greg McMullan ,  MRC Laboratory of Molecular Biology , Cambridge, UK;  Dr. Peter Moody ,  University of Leicester, UK ; and  Dr. Edmund Kunji ,  MRC Mitochondrial Biology Unit, Cambridge, UK  for helpful discussions and advice. This work was supported by grants from the  UK Medical Research Council  ( MC-A021-53019 ) and the  Wellcome Trust  ( WT089618MA ).
Data availability Data supporting the findings of this manuscript are available from the corresponding author upon reasonable request. A reporting summary for this Article is available as a Supplementary Information file. The cryo-EM maps of Etx pore have been deposited to the Electron Microscopy Data Bank under accession number EMD-4789 and the refined atomic coordinates have been deposited to the Protein Data Bank under accession number 6RB9. The source data for Fig. 1  and Supplementary Figs. 2, 12-15 are provided as a Source Data file.
Operation The code for the application is open-source and available on GitHub, which also includes a user guide. To run the application from a local machine, R needs to be installed with the Shiny package loaded. A single command can then be used to download the code for the application from GitHub and launch it in an interactive browser window. A demonstration version of the app is available at https://cathsmith57. shinyapps. io/HospMap/, which includes 'dummy' data that can be used to test the app. Extended data: Additional file 2  13  demonstrates the data import process: After selecting the file, a preview is displayed. The user must select the name of the column in the data set that represents each variable required to run the application. Pressing 'Run' then produces the interactive visualisations.
Ethical approval was not required for this study because it was undertaken as part of outbreak investigation and management, and personal identifiable information data were not used. Molecular characterisation. Samples were tested during the outbreak at the hospital's clinical virology laboratory by RT-qPCR directed at the ORF1/2 conserved region  15. A subset of specimens were then retrospectively analysed at the Virus Reference Department, Public Health England to confirm that norovirus RNA was still detectable, before further characterisation as described below. Detected norovirus strains were genotyped as previously described  16  , through analysis of nucleotide sequence representing the S-domain of the VP1 protein. For GII. 4 norovirus strains, further characterisation was performed through sequencing of the hypervariable P2 domain of the VP1 protein, as previously described  17.
This method has been shown to provide sufficient resolution to identify intra-genotypic variants, and to discriminate between strain transmission within an outbreak and separate introduction or events  18. Sequence analysis, generation of consensus sequences and pairwise alignments of sequences were performed using Bionumerics v6. 1 (Applied Maths, Kortijk, Belgium). MEGA software is an open access alternative that could also be used for this analysis. Epidemiological analysis. We described the age and sex distribution of cases. We classified cases as hospital-acquired if their first positive specimen was taken on or after the third day of admission and calculated the proportion of cases that met this definition. We plotted the cases according to genotype (and sub-strain for GII. 4 isolates) and sampling ward on a timeline.
This showed that the hospital-acquired infections were mostly diagnosed on the EC (elderly care) ward, with the remainder on the AAU (acute admissions unit). Adding community-acquired cases back on to the chart showed that additional community-acquired cases were diagnosed on the ID (infectious diseases) and oncology wards. The interactive timeline visualisation displays, in each row, a patient's duration of stay in the hospital (Extended data: Additional file 4  20  ; Figure  2b ). We used the options to order the patients in the timeline according to the date on which their positive sample was taken, and to colour code the timeline according to the ward that the patient was in on different days during their admission. This highlighted two clear groups of cases sampled around the same time on AAU and EC wards.
The availability of clinical samples that accurately represent all cases and epidemiological data accurately describing patient and staff movements during the outbreak may not be possible to collect in all incidences. Additionally, information on differences in severity of disease, duration of virus shedding, virus load and symptoms of disease may not always be collected and can be difficult to obtain retrospectively. However, together these factors are likely to have an important role in transmission during an outbreak. The main advantages of using the HospMapper software are its interactivity and flexibility. Although in this study we have used it to investigate an outbreak of norovirus, it could be used for any infection, with the capability to adjust parameters to appropriate values. It can also be used for any hospital or healthcare setting, as the depiction of wards is calculated automatically by the software.
The interactivity allows data to be explored quickly and without a priori hypotheses. It also means that the impact of assumptions about the data can be tested easily, for example, by adjusting the number of days of admission required for infections to be classified as hospital-acquired. A further advantage is the use of the open source R software and Shiny application framework. Knowledge of R is not required to run the application, but the code is free to download and could be customised or extended by users familiar with the software. The application also does not require complex computational infrastructure, and could therefore be used even in remote or decentralised healthcare settings. Shiny applications are run locally and do not require upload of any patient information to the internet, thereby ensuring that there are no issues with security of potentially-sensitive information.
(2018). Briefly, the test consisted of 180 • body rotations in response to visual stimuli which indicated the side of the rotation. The player started in an upright standing position with their feet placed in a parallel position. Two meters in front of the athlete was an electronic device, which displayed the visual stimulus, and 5 m behind the athlete was an arrival gate. Application software Virtools generated real-time 3D visual lights (Virtools Software Suite 3. 5, Copyright© 2006 Dassault Systemes, France). The lights were composed of three balls of green colors modeled in 3D. The balls were similar in size and lighted with the same intensity. The device showed the side of the rotation: when the left light turned red, the player performed a left rotation and conversely when the right light turned red, the player performed a right rotation.
Collecting Data As in the study of  Zouhal et al. (2019) , participants' reaction times (RT) were obtained using an accelerometer, which was attached to the players' chest and connected via Bluetooth to a computer. It recorded the time between signal appearance and the beginning of the player's movement (e. g. , first foot's movement detected). The participants' movement times (MT) were collected using four cameras (SANYO HD) that were placed around the test area  (Zouhal et al. , 2019). On the pitch, the first exercise was devoted to learn how to turn quickly and how to initiate the body rotation. For this purpose, hoops were used to train players where to put their first press-hold, and then corridors were formed with slats to make them turn in the right direction (Figure  1 ). In fact, it is well known that a good placement of the support leg could be the best way to teach players how to return, in order to optimize CoD performance.
Purpose: The purpose of this study was to assess, using an anthropomorphic digital phantom, the accuracy of algorithms in registering precontrast and contrast-enhanced computed tomography (CT) chest images for generation of iodine maps of the pulmonary parenchyma via temporal subtraction. Materials and methods: The XCAT phantom, with enhanced airway and pulmonary vessel structures, was used to simulate precontrast and contrast-enhanced chest images at various inspiration levels and added CT simulation for realistic system noise. Differences in diaphragm position were varied between 0 and 20 mm, with the maximum chosen to exceed the 95th percentile found in a dataset of 100 clinical subtraction CTs. In addition, the influence of whole body movement, degree of iodine enhancement, beam hardening artifacts, presence of nodules and perfusion defects in the pulmonary parenchyma, and variation in noise on the registration were also investigated.
12, 13 The phantom, based on ICRP Publication 89 data, is commonly used in imaging research due to the flexibility of its nonuniform rational basis spline (NURBS)-based surface primitives, variation in anatomy, motion, and variable spatial resolution, that can be simulated. The patient motion was modeled using 4D-tagged magnetic resonance imaging data (cardiac motion) and 4D high-resolution respiratory-gated CT data (respiratory motion). 12 These advantages also make it ideal for evaluation of registration algorithms. 13 he XCAT phantom allows for the specification of more than 200 parameters, including contrast administration comparable to clinical practice, patient and scan characteristics, and respiratory and cardiac phase. This allows manipulation of the voxel values representing different tissues with enhanced attenuation due to the presence of intravenous-iodinated contrast agent.
2. C. Image simulation The values of the voxels in the XCAT phantom represent linear attenuation coefficients at a specific user-defined x-ray energy. To generate realistic phantom images, phantom realizations for x-ray energies were generated from 10 to 100 keV, in 1 keV steps. Using the TASMICS software from Hernandez and Boone,  14  an x-ray spectrum with a tube potential of 100 kV and an added filter thickness of 17. 4 mm aluminum was generated, resulting in a first half value layer (HVL) of 8. 28 mm Al. This first HVL value was similar to measurements on the CT scanner in our radiology department (Aquilion ONE GENESIS edition, Canon Medical Systems, Otawara, Japan). The monoenergetic attenuation values of each voxel were used in a polychromatic simulation to generate realistic CT images.
Data collection A standardised questionnaire was administered to each participant by trained nurses, midwives or social workers (psychosocial agents). The questionnaire was administered in French, the official language of the country, but each participant has the possibility to ask for a translator and a witness to assist in case she was not able to read or understand French. This questionnaire allowed the collection of data on demographics (age, education, marital status, monthly income), awareness of cervical cancer (existence of the disease, risk factors and prevention) and personal history of cervical cancer screening (date, place, provider, screening method, number of screening conducted). Additional HIV data (date of HIV infection diagnosis, history of CD4 count measures, clinical stage at enrolment into HIV care and antiretroviral therapy use) were extracted from the electronic records of the respective HIV clinics.
Acknowledgements We would like to warmly thank  Pr François Dabis  for his advises and orientation when designing and implementing the study, as well as  Mr Azany Jean Claude  for his strong support in data management and study monitoring. Contributors BT and AJ designed the study. All authors supervised the study implementation and data collection. Statistical analysis was performed by BT, SB and AJ. Data interpretation and first draft of manuscript was done by BT, SB, JJK and AJ. Critical revision of the manuscript for important intellectual content was provided by all the coauthors who read and commented on the original manuscript and all agreed on the version finalised by BT, SB and AJ for submission. Funding The study was conducted under the  IeDEA West Africa collaboration grants  funded by the  National Cancer Institute (NCI) ;  Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) ;  National Institute of Allergy and Infectious Diseases (NIAID) ; Grant number:  5U01AI069919.
Search strategy and eligibility criteria Search methods for identification of relevant studies was conducted on 10, November 2018, using the below four electronic databases: Ovid MEDLINE(R) Epub Ahead of Print, In-Process and Other Non-Indexed Citations, Ovid MEDLI-NE(R) Daily and Ovid MEDLINE(R) 1946 to Present PubMed http://pubmed. gov Embase. com https://www. embase. com/#search Cochrane Library www. thecochranelibrary. com The search strategy principle was based on dividing the topic into three concepts: (1) economic burden, (2) surgical site infection, and (3) antimicrobial resistance. All searches were limited to human and English language with no restriction on age or publication date to ensure that search results include all published articles pertained to the topic. Ovid Medline was first searched to identify all the possible medical subject headings (MeSH) terms with their corresponding keyword equivalences to increase sensitivity of the search strategy.
After finalizing Medline strategy, the search terms were appropriately adapted into the three other databases. The obtained results were screened and studies were excluded if their primary objective was not solely the evaluation of the burden of surgical site infection. Further reading and screening articles showed that it is not possible to quantify the burden of SSI if the accuracy and reliability of data is questionable due to gaps in surveillance and epidemiology methods and it was also not possible to discuss AMR prevention without further highlighting the gaps in current SSI infection and prevention practices. Further search included articles through gray literature and organizational publications (i. e. National Institute for Health and Care Excellence, Centers for Disease Control and Prevention, World Health Organization and European Center of Disease Prevention and Control).
The three most common economic evaluation tools are cost-effectiveness analysis, cost-utility analysis, and cost-benefit analysis; they differ in the nature of the measured consequences. Of note, the cost-of-illness analysis does not measure the outcomes but only the related costs of the disease. This type of study is considered a baseline to inform health-economic analysis. Literature review shows the uses of different study designs  [53, 65, 69] , and inappropriate allocated type of healtheconomic analysis. (  9 ) Sources of data and methodology of data collection can be an important source of bias especially if not explicity described, if single-centered and collected retrospectively from hospital databases regardless if generated from high or LMICS. (  10 ) SSI is a time-dependent exposure.
The Chinese government is now prioritizing population health, and has made several considerable health investments and promotion actions, such as conditional approval of the nonavalent HPV vaccine following introduction of bivalent vaccine and quadrivalent vaccine in mainland China. 15 Understanding the burden of HPV-attributable cancer can boost not only programs of HPV vaccination but also HPV-based cancer screening in China, and can provide basic data for cost-effective evaluation of these intervention programs. Moreover, it is essential to monitor trends in HPV-attributable cancer incidence that might result from future increasing use of HPV vaccines and changes in cervical cancer screening practices. In this work, we calculated the cancer burden attributable to HPV infection for the year 2014 by cancer site, sex, geographical area and age.
| Data sources Age-specific rate of cancer cases and deaths was obtained from the annual report of Chinese cancer registry published in 2018. 16, 17 Since the typical population-based cancer registry has three years of time lags from cancer incident to data collection, the data we extracted was actually the cancer cases or deaths occurred in 2014. 16, 17 In 2014, 449 cancer registries (160 in urban areas and 289 in rural areas) from all 31 provinces in mainland China submitted cancer registry data to the National Central Cancer Registry. 16, 17 These cancer registries covered 346 million persons (176 males and 170 females), accounting for about 25. 27% of the national population. 16, 17 All submitted cancer registry data underwent quality control based on the criteria of "Guideline for Chinese Cancer Registration" and "Cancer Incidence in Five Continents Volume IX".