dataesr/scientific-paragraphs-categorization huggingface dataset:
Histological analysis was performed blind by a pathologist who was not aware of the clinical scores of the mice. Information on microscope image acquisition. Make and model of microscope: Zeiss Imager A1; Type, magnification, and numerical aperture of the objective lenses: Zeiss Plan-NEOFLUAR 56/0. 16 Zeiss Plan-NEOFLUAR 406/0. 75; Imaging medium: air; Camera make and model: Zeiss AxioCam ERc 5s (with 0. 5 adapter); Acquisition software: Zeiss AxioVision. Count of inflammatory foci. Inflammatory foci of approximately 20 cells were counted in each H&E stained section. When inflammatory infiltrates consisted of more than 20 cells, an estimate was made of how many foci of 20 cells were present. Estimation of demyelination. The demyelination score represents an estimate of the demyelinated area for each section as follows: 0 -no demyelination (less than 5% demyelinated area); 1-5 to 20% demyelinated area; 2-20 to 40% demyelinated area; 3-40 to 60% demyelinated area; 4-60 to 80% demyelinated area; 5-80 to 100% demyelinated area For Luxol fast blue stained slides, the size of the demyelinated area was estimated based on less intense blue staining of myelin.
This is similar to what is seen in standard MOG35-55/CFA-induced EAE and is not observed in IFA controls (data not shown). Demyelination is considered difficult to estimate in brain sections of mice with EAE, demyelination levels are usually not assessed in brains of mice with standard MOG35-55-induced EAE. Since this MSRV-Env model is novel, an attempt was nonetheless made to estimate the demyelination in the brain sections. Between 3 and 8 inflammatory foci were found in each analyzed section for both mice. In the Luxol fast blue stained sections, demyelination score was 1 to 3 in areas of inflammation. In H&E stained sections we estimated the percent of inflamed areas with interruption of normal structure, with pallor and vacuolation consistent with edema and demyelination (Cf. Figures S10 to S21 in File S1).
Apoptotic cells were also found in 4 of 6 of these sections (4 to 9 apoptotic cells/section). Inflammatory infiltrates consisted predominantly of mononuclear cells. Demyelination was detected in both H&E and Luxol fast blue stained sections. The number of inflammatory foci, the number of apoptotic cells and the severity of demyelination were consistent with the clinical scores (for detailed Tables, see section II and annexed raw data of File S1). Such histological aspects of the lesions in the spinal cords and brains of Env-induced EAE mice were not different from the findings typical of standard EAE. In addition, brain lesions with marked demyelination were readily detectable in MSRV-Env induced EAE. Similar histological analysis was performed on an additional case, mouse 2-5, which had significant weight loss during the first 2 weeks after immunization but which did not develop clinically detectable paralysis during the study period, in order to address potential lesions in a sub-clinical phase of EAE.
Our data demonstrate that mice injected with MSRV-Env in the presence of MOG 35-55 peptide clearly developed EAE. Demyelinating neuroinflammation in the CNS was confirmed by neurohistological analysis. In addition, significant inflammatory and autoimmune responses against the MOG35-55 peptide were revealed. The body weight changes suggest that this new model of EAE may be remitting-relapsing, with the first wave of EAE being subclinical. Similar clinical observations are often made in SJL mice, in which some mice develop a very mild, barely detectable first wave of EAE (with only a single day of clinically detectable paralysis, with a score of 0. 5), but go on to develop a significant relapse 10-15 days later, with a score of 2. 0 or greater  [6, 9]. The body weight changes and histological analysis suggest that in addition to the mice with clear, clinical signs of EAE, additional mice developed CNS inflammation which was not detected in the clinical examination during the time limits of the present study.
Acknowledgments We thank  Vanessa Cingala  and  Arthur Derour-Corthe  for providing support,  Sylvain Buffet  for designing the phylogenetic tree and providing sequence analysis, and  Hubert Lepidi  for performing immunohistochemical analysis. Dr Mahamat  is an infectious diseases physician and head of the infection control unit at the  General Hospital of Cayenne, French Guiana. His research interests include emerging disease surveillance, outbreak reports and quasi-experimental studies using times series analysis.
We tested this by digesting the purified material with several different proteases. ). These results confirmed the peptidic nature of the Vel-specific 18 kDa band. In contrast, this 18 kDa band appeared to be largely resistant to trypsin (Fig 2C, lane 9), which explained a posteriori the failure of our previous attempts to identify the Vel antigen carrier protein by mass spectrometry analysis after in-gel trypsin digest. Hence, we digested the purified 18 kDa band with chymotrypsin prior to mass spectrometry analysis. Disappointingly, analysis of the mass spectrometry data using the standard program SEQUEST  (Eng et al, 1994)  did not yield a positive identification for the 18 kDa band. Given the relatively small size of the protein carrying the Vel antigen, we had anticipated that its identification would ultimately be determined by relatively few chymotryptic peptides.
We had therefore collected the mass spectra for both precursor and fragment ions in a high resolution orbitrap mass spectrometer as this would facilitate de novo peptide sequencing if standard analysis programs were to fail. We initiated de novo peptide sequencing of our mass spectra using the program PepNovo  (Frank & Pevzner, 2005)  setting the parameters to identify six residue sequence tags. We manually subjected the top 25 PepNovo-identified hexamer tags to a BLAST search  (Altschul et al, 1990)  and found that 19 of these hexamer tags were consistent with their mapping to autocatalytic chymotryptic peptides (Supporting Information Table  S1 ). However, three of the six remaining hexamer tags (GKLGIA, ESHVHY and PQESHV) were consistent with their mapping to the uncharacterized protein LOC388588 (Supporting Information Table  S1 ).
Manual de novo extension mapped these three hexamer tags to three individual, distinct peptides of different precursor masses that covered the following amino acids of LOC388588: CTGKLGIAM, PQESHVHY and MQPQESHVHY. Of note, although the hexamer tags ESHVHY and PQESHV overlap, they originated from entirely different tandem mass spectra resulting from chymotryptic digestion yielded both peptides PQESHVHY and MQPQESHVHY. spectrum and de novo annotations for the peptide PQESHVHY; the exquisite resolution of the orbitrap mass spectrometer gave less than 1 part per million (PPM) mass accuracy for both parent and identified daughter ions. LOC388588 was initially identified by the MGC Program Team  (Strausberg et al, 2002)  as a hypothetical protein predicted to be a single-pass membrane protein  (Fig 3B).
These obstacles were overcome first thanks to a potent anti-Vel, which we succeeded to use for Western blot analysis. All our attempts with other anti-Vel were unsuccessful. Secondly, the fortuitous observation that SMIM1 runs at distinctly different molecular weights under reducing and non-reducing conditions provided the basis for a unique purification strategy. Several attributes of purified SMIM1, however, made its identification refractory to standard mass spectrometry workflows: (i) SMIM1 was nearly untouched by trypsin, the workhorse enzyme in bottom-up proteomics; (ii) SMIM1 is small and even the few possible chymotryptic peptides were not identified by a standard proteomic search algorithm in spite of the good fortune that SMIM1 (i. e. LOC388588) was indeed in the proteomic database that we searched; (iii) SMIM1 would not have been identified without the non-standard acquisition of high resolution MS/MS data and manual de novo peptide sequencing.
For tryptic peptides, precursor scans (360-1600 m/z) were conducted in the orbitrap followed by 10 data-dependent MS/MS spectra in the linear ion trap. Chymotryptic peptides were analyzed similarly except that all data were acquired in the orbitrap. Dynamic exclusion was enabled with a repeat count of three and a repeat cycle of 180 s. Lock mass was enabled and set to calibrate on the mass of a polydimethylcyclosiloxane ion  ([(Si(CH 3 )   (Eng et al, 1994)  were conducted as described previously  (Ballif et al, 2008)  except that dynamic carbamidomethylation of cysteine was permitted and for chymotryptic searches no specific enzyme specificity was required. De novo sequencing was initiated with the program Pepnovo  (Frank & Pevzner, 2005)  by loading RAW files to the University of California at San Diego's Center for Computational Mass Spectrometry Pepnovo server where the following selections were made: high accuracy instrument, methionine oxidation, cysteine carbamidomethylation, no protease, parent ion tolerance of 0.
Genomic DNA sequencing and data analysis The full-length SMIM1 gene was amplified with primers LOC388588-1 and LOC388588-6 (Supporting Information Table  S2 ) from genomic DNA isolated from whole blood using the Wizard Genomic DNA Purification Kit (Promega). The corresponding PCR product was purified with SureClean Plus (Bioline) and sequenced by ABI BigDye terminator chemistry (GATC Biotech) with primers LOC388588-7 and LOC388588-4, and LOC388588-5 in case of heterozygosity for the deletion c. 64_80del17. Of note, the two coding exons of SMIM1 can be amplified with primers LOC388588-3 and LOC388588-6, and sequenced with LOC388588-4 and LOC388588-5. Sequencing data were analyzed with DNA Workbench software (CLC bio) and Mutation Surveyor software (SoftGenetics). Mutation numbering relates to the reference sequence of SMIM1 mRNA (NM_001163724.
Acknowledgements We thank  Sylvie Poupel ,  Sirandou Tounkara ,  Dominique Gien  and  Ngone Camara  for their technical help, as well as all the other present and past members of the  CNRGS  for identifying and cryopreserving VelÀ blood samples. This study was supported in part by the  INTS, Inserm and Paris Diderot University  (Paris 7). B. A. B. was supported by the  Vermont Genetics Network  through  NIH  Grant  8P20GM103449  from the  INBRE program  of the  NCRR/NIGMS.
Library Trusted evidence. Informed decisions. Better health. Cochrane Database of Systematic Reviews exacerbation of chronic obstructive pulmonary disease (COPD); or an upper ARI including common cold, rhino-sinusitis, pharyngitis, tonsillitis, or otitis media. We also included people with sepsis and suspected ARIs in the analyses. We excluded trials if they focused exclusively on children or used PCT to escalate antibiotic therapy. We made no exclusions based on language of reports or clinical setting. We included trials from primary care, emergency departments, and medical and surgical ICUs.
Electronic searches We updated the searches for this review in February 2017, running the search across all databases from the date of inception to 10 February 2017. We screened all new references identified by the search. We searched the following databases for published studies: • The Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 1), part of the Cochrane Library, which includes the Cochrane Acute Respiratory Infections Group's Specialised Register, www. cochranelibrary. com/ (accessed 10 February 2017) (Appendix 1); • MEDLINE Ovid (1966 to 10 February 2017) (Appendix 2); • Embase. com (1980 to 10 February 2017) (Appendix 3). We used the search strategy in Appendix 4 to conduct searches for the 2012 version of this review (Schuetz 2012). We also searched for ongoing and completed trials in the following trial register: • US National Institutes of Health Ongoing Trials Register ClinicalTrials.
Results of the search A er removal of duplicates, we identified 998 records that we further assessed based on title and abstracts, excluding 919 records. We obtained 79 full-text study reports, and following assessment excluded 39 that did not meet our inclusion criteria. Eight studies were ongoing trials. Cochrane Database of Systematic Reviews participant data meta-analysis (see Figure  1 ). We did not obtain individual participant data for four trials, and two trials did not include participants with confirmed ARIs. The sensitivity aggregate analysis includes all 32 trials. We included a total of 26 studies involving 6708 participants in the main individual participant data meta-analysis. Study characteristics are presented in Table  1.
Ongoing studies Our searches of the trial register identified seven ongoing studies that we will assess for inclusion for the next review update (Ongoing studies). These studies focus on the utility of PCT in people with pneumonitis (NCT02862314), pulmonary embolism (NCT02261610), lower respiratory infection (NCT02130986), heart failure (NCT02787603), and intraoperative positive-end expiratory pressure optimisation (NCT02931409). Two trials are antibiotic e icacy trials (NCT02332577; NCT02440828).
Library Trusted evidence. Informed decisions. Better health. Cochrane Database of Systematic Reviews (adjusted coe icient -2. 45 days, 95% CI -2. 86 to -2. 05) contributed to the lower overall exposure in the emergency department setting. Length of hospital stay and ICU stay were similar in both groups with no evidence for di erent e ects in subgroups (P for interaction > 0. 05).
Interventions Guiding antibiotic decisions in ICU patients with proven bacterial infection Algorithm used in this study: All participants received antibiotic therapy. For the control group, stopping antibiotic therapy was at the discretion of the attending physician. For the intervention group, physicians were guided by the PCT protocol to stop antibiotic treatment. The protocol stated 2 conditions: 1) PCT dropped more than 90% from the peak level, or 2) an absolute value < 0. 5 ng/mL was reached. Follow-up time: Data were recorded from 2 days before the bacteraemia (when applicable), with day 0 defined as the day sepsis was diagnosed, until 14 days after or at ICU discharge, whichever came first. Registration: NCT01494675.
Cochrane Database of Systematic Reviews Algorithm used in this study: Procalcitonin levels were measured via outsourcing to SRL (Tokyo, Japan); the results were obtained 2 or 3 days after admission. In the PCT group, if the PCT levels upon admission were < 0. 5 ng/mL, 0. 5 to 1. 0 ng/mL, or > 1. 0 ng/mL, the duration of antibiotic therapy was determined to be 3, 5, or 7 days, respectively. If the PCT level upon admission was 45. 0 ng/mL, antibiotic treatment was continued until it was less than 10% of the peak PCT level reached. In the control group, antibiotic therapy followed the recommendations of the Japanese Respiratory Society guideline for management of community-acquired pneumonia in adults. Antibiotic therapy was discontinued if 3 of the following 4 criteria were met: fever declined (body temperature < 37.
Interventions Guiding antibiotic decisions in people with severe exacerbations of COPD Algorithm used in this study: On admission, all patients received a 3-day course of antibiotics (either amoxicillin plus clavulanate or quinolones) according to 2005 international guidelines. Procalcitonin levels were measured on hospital admission, on day 1, and on day 2. On day 2 each eligible patient was randomly assigned to 1 of the 2 treatment plans. quote "Participants randomised to the standard group continued antibiotic therapy for 10 days, whereas participants randomised to the PCT group either continued treatment for 10 days or stopped on day 3, depending on their PCT levels, according to previously recommended cut-o values. Specifi- Cochrane Database of Systematic Reviews cally, participants continued antibiotic treatment for 10 days if 1 or more of the PCT values on the first 3 days of hospitalisation were 0.
Library Trusted evidence. Informed decisions. Better health. Cochrane Database of Systematic Reviews Methods Randomised, single-centre, single-blinded, controlled clinical trial in the Beijing Luhe Hospital, China Participants Inclusion criteria: Patients with AECOPD who were 40 years of age, had sound understanding and language abilities, and who had a PCT level < 0. 1 ng/mL were included. Exclusion criteria: Fever (38°C), tracheal intubation within 24 h after hospital admission, a PCT level of 0. 1 ng/mL on admission, pneumonia, chronic renal failure, history of malignant disease, immunosuppressive therapy, and refusal to participate Included in this study: 194 randomised participants. 191 finished the 30-day follow-up.
Cochrane Database of Systematic Reviews In addition, based on referee comments during the initial editorial process of the initial review (Schuetz 2012), we added further sensitivity analyses to investigate the robustness of our results. Specifically, we performed sensitivity analyses excluding trials with low adherence to PCT algorithms (< 70%) or not reporting adherence. We also performed sensitivity analyses with respect to methodological quality criteria (allocation concealment and blinded outcome assessment). We further performed a sensitivity analysis excluding trials with a follow-up time for mortality di erent than one month. We conducted meta-analyses with aggregated data of included trials to further investigate heterogeneity (inconsistency measure I 2 statistic and Cochran Q test) of intervention e ects and trial subgroups based on adherence to PCT algorithms.
proportion of participants receiving antibiotics at day 5 post randomisation • death at day 5, at ICU discharge, and at hospital discharge • proportion of participants started on antibiotics post randomisation • duration of antibiotic exposure • SOFA score at day 3 and day 5 proportion of participants with infection acquired between randomisation and day 3, day 5, and ICU discharge • ICU and hospital length-of-stay Notes Funding: Research grant partly by Thermo Fisher B•R•A•H•M•S France. The sponsor had no input in study design, conduct, or reporting. Follow-up time: Until hospital discharge or 30 days' post randomisation, whichever came first Registration: NCT01025180.
Schuetz P, Chiappa V, Briel M, Greenwald JL. Procalcitonin algorithms for antibiotic therapy decisions: a systematic review of randomized controlled trials and recommendations for clinical algorithms. Archives of Internal Medicine 2011;171(15):1322-31. Cochrane Database of Systematic Reviews procalcitonin concentrations in addition to symptoms and signs to predict pneumonia in patients presenting to primary care with acute cough: diagnostic study. BMJ 2013;346:f2450.
Cochrane Database of Systematic Reviews PCT guidance with an allocation ratio of 1:1:1:1 by use of a central randomisation web server. Randomisation was stratified by study centre, sex, and sepsis severity" Research grant from the Départment à la Recherche Clinique et au Développement, Assistance Publique-Hopitaux de Paris (PHRC AOR06019), France. B•R•A•H•M•S, Germany (manufacturer of PCT assay) provided all assay-related materials free of charge for the study (Kryptor machines if not already available on-site and kits and maintenance required for study-related measurements). 300/685 screened patients were eligible for the study, of whom 151 were randomised to the intervention group and 149 to the non-intervention group In the standard care group standard-of-care testing (bacterial and viral cultures of respiratory samples, hospital influenza/RSV duplex PCR, and urine Legionella antigen analysis) were obtained on admission and antibiotic decisions were made by the attending physician.
All patients with suspected AE-IPF admitted to the respiratory department were assessed for eligibility from January 2009 to December 2011. Acute exacerbation of idiopathic pulmonary fibrosis was defined according to the criteria established by the Idiopathic Pulmonary Fibrosis Clini-Cochrane Database of Systematic Reviews raphy with new bilateral ground-glass; (4) abnormality and/or consolidation superimposed on a background reticular or honeycomb pattern consistent with usual interstitial pneumonia pattern; (5) no evidence of pulmonary infection by endotracheal aspirate or bronchoalveolar lavage; (6) exclusion of le heart failure, pulmonary embolism, and identifiable cause of acute lung injury. Exclusion criteria: Patients treated with antibiotics during the previous 2 weeks were excluded.
Cochrane Database of Systematic ReviewsOutcomes• antibiotic use, expressed as rate of antibiotic prescriptions in percentage and relative risk of antibiotic exposure • measures of treatment success • length of hospital stay • clinical, laboratory, and spirometry outcomes at discharge • results of spirometry at the 12-month follow-up examination, as well as the results of the Asthma Control Test, the results of the Asthma Quality of Life Questionnaire at the 12-month follow-up visit • clinical events during the 12-month follow-up period, including numbers of asthma exacerbations, ED visits, hospitalisations, and need for systemic corticosteroid use for treatment of asthma Notes Funding: The study was sponsored by a grant from the Shanghai Fi h People's Hospital Science Foundation and Minhang District Natural Science Foundation of Shanghai.
Cochrane Database of Systematic Reviews 2. have undergone oro-tracheal intubation for a coma (Glasgow Coma Score ≤ 8) 3. with mechanical ventilation initiated in the first 48 hours following hospital admission Experimental: Optimal PEEP patients submitted to general anaesthesia and open radical cystectomy and urinary diversion (20 participants) will be submitted an alveolar recruitment maneuver using the sustained airway pressure by the CPAP method, applying 30 cmH 2 O PEEP for 30 seconds followed by a decremental PEEP titration procedure directed by static pulmonary compliance (Cstat). During PEEP titration procedure, PEEP will be decreased from 14 cmH 2 O by 2 cmH 2 O every 4 minutes, until a final PEEP of 6 cmH 2 O. Optimal PEEP is considered to be a PEEP value resulting the highest possible Cstat measured by ventilator.
•• proportion of participants receiving antibiotics at day 5 post randomisation • death at day 5, at ICU discharge, and at hospital discharge • proportion of participants started on antibiotics post randomisation • duration of antibiotic exposure • SOFA score at day 3 and day 5 proportion of participants with infection acquired between randomisation and day 3, day 5, and ICU discharge • ICU and hospital length-of-stay Notes Funding: Research grant partly by Thermo Fisher B•R•A•H•M•S France. The sponsor had no input in study design, conduct, or reporting. Follow-up time: Until hospital discharge or 30 days' post randomisation, whichever came first Registration: NCT01025180.
Cochrane Library Trusted evidence. Informed decisions. Better health. Cochrane Database of Systematic Reviews Long 2014 {published data only} Stolz 2007 {published data only} Long W, Li LJ, Huang GZ, Zhang XM, Zhang YC, Tang JG, et Stolz D, Christ-Crain M, Bingisser R, Leuppi J, Miedinger D, al. Procalcitonin guidance for reduction of antibiotic use Muller C, et al. Antibiotic treatment of exacerbations of COPD: a in patients hospitalized with severe acute exacerbations of randomized, controlled trial comparing procalcitonin-guidance asthma: a randomized controlled study with 12-month follow-up. Critical Care 2014;18(5):471. with standard therapy. Chest 2007;131(1):9-19. De Jong 2016 {published data only} De Jong E, van Oers JA, Beishuizen A, Vos P, Vermeijden WJ, Stolz 2009 {published data only} Maravić-Stojković 2011 {published data only} Maravić-Stojković V, Laušević-Vuk L, Jović M, Ranković A, Borzanović M, Marinković J.