dataesr/scientific-paragraphs-categorization huggingface dataset:
The strength of this study is that it is the largest to date to assess the association between ART and cardiometabolic risk in SSA using IPD. In addition, we defined cardiometabolic risk factors according to clinically relevant cut-offs. Our findings may therefore be relevant for the clinical care of patients. Further, use of IPD enabled a more comprehensive adjustment for potential confounders including BMI and socio-demographic factors, as well as behavioural risk factors at the individual level. Importantly, the study assessed data on the class of ART thereby shedding more light on the impact of ART drug class on lipids, which is relevant to HIV patient treatment and care. However, the study has some limitations. First, the majority of the studies included in the pooled analysis were crosssectional.
Acknowledgements The authors are grateful to the study participants and the research teams of the studies included in these analyses for their effort in generating these data. The authors are also grateful to the colleagues at the  Global Health and Population Sciences Group, University of Cambridge , for their useful comments. MS, KE, EY and PK are part-funded by the  African Partnership for Chronic Disease Research (Medical Research Council  UK partnership grant number  MR/ K013491/1 ). KE is supported by an  Islamic Development Bank Cambridge International Scholarship. MS is supported by the  National Institute for Health Research Cambridge Biomedical Research Centre (UK).
Background and study aims Colon capsule endoscopy (CCE) does not possess an objective and reliable scoring system to assess the quality of visualization of the colon mucosa. The aim of this study was to establish a colonic computed assessment of cleansing (CAC) score able to discriminate "adequately cleansed" from "inadequately cleansed" CCE still frames. Patients and methods Twelve normal and complete CCEs, using the Pillcam Colon 2 system (Medtronic, Minnesota, United States), were prospectively selected amongst a database. A CAC score, defined as the ratio of color intensities red over green (R/G ratio), and red over brown (R/(R + G) ratio) was calculated for each extracted colonic frame. After sorting and random selection, two sets of still frames representative of the range of these ratios were obtained.
Capsule image computerized analysis and selection For every CCE2 video sequence, each still frame was individualized and de-identified. Color intensities in the red (R), green (G) and blue (B) channels of each individual frame were identified using MATLAB R2014a software (MathWorks, Natick, USA) running on a commercially available solid-state hard drive (8 Go RAM, 2. 9 GHz Intel Core Processor). Our hypothesis, similar to that of Van Weyenberg et al. [15]  at the tissue color bar level, was that a still frame showing good-quality preparation is associated with high values of red intensity and low values of green intensity (higher R/G ratio), whereas a still frame with poorquality preparation is associated with low values of red intensity and high values of green intensity (lower R/G ratio).
584. Distribution of the ratio values was determined, and based on the range between the lowest and highest ratio value, equal intervals were created (▶ Fig. 1 ). Eighteen intervals of a 0. 05 value were created for the R/G ratios. Sixteen intervals of a 0. 01 value were created for the R/(R + G) ratios. Twelve still frames per interval per CCE2 procedure were then randomly selected and included in the datasets. All in all, 216 still frames were included in the R/G set and 192 in the R/(R + G) set.
For instance, in 2011, Van Weyenberg et al. [15]  published the first study using a computed quantitative scale to assess mucosal visibility dur- ▶ Fig. 1  Colon capsule still frame computed assessment of cleansing (CAC) score distributions, for red over green (R/G ratio), and for red over brown R/(R + G) ratio. ▶ Table  1  Results of the experts' readings and agreement of the two datasets of colon capsule still frames. R/G, ratio of red over green; R/(R + G), ratio of red over brown ▶ Table  2  Diagnostic performance of computed assessment of cleansing score, according to cut-off values of R/G and R/(R + G) ratios. ing SB-VCE. The results suggested that a computed scoring system based on color intensities in the red and green channel of the tissue color bar could be used to assess quality of cleansing.
A sensitivity analysis will be conducted in the population of patients for whom the criteria of switching from NIV to spontaneous breathing, or conversely, are not strictly verified. Ethics and dissemination The protocol has been approved by the Comité de Protection des Personnes (CPP) Sud-Ouest & Outre-Mer IV (ref CPP17-049a/2017-A01830-53) and will be carried out in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. A trial steering committee will oversee the progress of the study. Findings will be disseminated through national and international scientific conferences, and publication in peer-reviewed journals. trial registration number NCT03406572.
Protocol feasibility We will undertake a preliminary pilot study in five centres before conducting the full-scale research project. This preparatory phase will last 5 months (including an enrolment period of about 3 months) and seek to recruit approximately 24 patients. We aim to address current uncertainties regarding the feasibility of performing the assessments for switching between NIV and SB according to the study protocol. The outcomes to assess feasibility are described in box 4. The key criterion for evaluating the success of the pilot study is that at least 90% of patients will have valid and complete VFDs data. Failure to reach these criteria does not necessarily indicate unfeasibility; rather, it underlines modifications to be made in the protocol. Data from the pilot phase will be included into the final analysis if no modification has been made in the assessment of the VFDs.
Sample size calculation The most recent large study dataset on hypercapnic respiratory failure patients comes from the EchoICU trial. 10 n that study, mean duration of NIV was 5. 2 days. Fifteen per cent of patients failed NIV and required intubation. A total sample size of 242 patients (121 in each group) was determined necessary to detect as statistically significant a decrease of 40% of ventilator support duration in the HFHO group, with a power of 90% and an alpha risk of 0. 05. The sample size calculation was based on the following assumptions: mean number of VFDs between day 0 and day 28 of 21. 3 in the standard O 2 group, which is congruent with EchoICU trial data  8  ; mortality rate at day 28 of 10%  11  and equal in both groups; a loss to follow-up rate of approximately 10%.
Statistical analysis Data will be analysed using SAS software (V. 9. 4 or higher). A flow chart will describe the number of eligible patients, the number of patients effectively included in the study and in each of the two groups. Demographic and clinical characteristics of the study patients at baseline and at each follow-up visit will be reported with frequencies and percentages for categorical variables, and with mean, SD, median and IQR for continuous variables. This description will be performed for all patients and for each group. All analysis for the primary and secondary outcomes will be performed in the intention-to-treat population. All tests will be two-sided with a statistical significance of 5%.
Patient and public involvement The research question was developed thanks to our patients' input and experience with NIV and nasal high flow. Patients are regularly questioned on the benefits of these techniques regarding comfort and tolerance. Patients' constant feedback during routine care therefore helped us assess the burden of the intervention and establish the study design. For example, our initial design of the study included evaluation of patients' respiratory parameters and interruption of NIV during night time. Based on the patients' feedbackthat it would be best for their own comfort, not to be woken up for the assessment-we modified the study protocol, so as to preserve their sleep. Results of the trial will be made available to all participants via ClinicalTrials. gov as well as by email notification.
data collection and quality control The persons responsible for the quality control of clinical matters will take all necessary precautions to ensure the confidentiality of information relating to the study participants. These persons, as well as the investigators themselves, are bound by professional secrecy. During or after the research, all data collected about the participants and sent to the sponsor by the investigators (or any other specialised collaborators) will be anonymised. Under no circumstances should the names and addresses of the subjects involved be shown. In any case of premature withdrawals and exits, the investigator must document their reason(s) and try to collect primary endpoint, secondary endpoints and safety assessment, if the participant agrees. If a participant exits the study prematurely or withdraws consent, any data collected prior to the date of premature exit may still be used, excepted if the participant refuse in writing.
A data monitoring committee (DMC) is not required for this research with minimal risks for the following reasons: (1) the devices have been used in routine for many years, and so we have enough perspective regarding their safety; (2) none of the three international experts who reviewed the protocol during the funding application process stressed the need for a DMC and (3) according to the French law, research with 'minimal risks' does not require a DMC. The research data will be collected and monitored using an eCRF through CleanWEB Electronic Observation Book and will be centralised on a server hosted by the AP-HP Operations Department. This research is governed by the CNIL 'Reference Method for processing personal data for clinical studies' (MR-001, amended). AP-HP, the sponsor, has signed a declaration of compliance with this 'Reference Method'.
20 Taken together, these data suggest that patients with hypercapnic ARF could also benefit from this technique. strengths and limitations This is the largest prospective multicentre RCT comparing standard O 2 to HFHO in the field of hypercapnic ARF. Very strict criteria to initiate, stop and resume NIV will be used to ensure that all centres will apply the technique similarly. A consensus on these criteria has been reached through a two-round Delphi survey. A pilot study will assess the feasibility of these criteria for the trial. Regarding the blinding, because of the nature of the study and the devices evaluated, it is not possible to blind patients nor the investigators to the allocation group. However, all the analyses will be carried out in a blinded manner. In conclusion, the 'High Flow-ACRF' trial is an investigator-initiated RCT empowered to test the hypothesis that HFHO in comparison to standard O 2 in-between breaks of NIV sequences may increase the number of VFDs in patients with hypercapnic ARF.
Furthermore, the duration of benefit associated with 'salvage' chemotherapy for progression decreases with each subsequent line of treatment. 8, 9 here remains an unmet need for effective and well-tolerated long-term maintenance treatment options for patients with recurrent ovarian cancer to maintain quality of life and delay the need for further chemotherapy, particularly after response. Olaparib (Lynparza™), a poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitor, is approved (tablet formulation) for treatment in the maintenance setting for patients with platinumsensitive relapsed ovarian cancer, irrespective of BRCA1/2 mutation (BRCAm) status. 10, 11 e have previously reported data from Study 19 (NCT00753545), a Phase II trial that assessed the efficacy and safety of olaparib maintenance monotherapy in platinum-sensitive, recurrent high-grade serous ovarian cancer patients, and showed a significant improvement in PFS with maintenance olaparib vs placebo (hazard ratio (HR) 0.
Study design and population Study 19 was a Phase II, randomised, double-blind, placebocontrolled trial (NCT00753545). Eligible patients were at least 18 years old, with recurrent ovarian, fallopian tube or primary peritoneal cancer with high-grade serous histology and were platinum sensitive. Patients had received two or more prior courses of platinum-based chemotherapy and were in complete or partial response to their most recent regimen (Supplementary Methods). Additional eligibility criteria have been described previously. 5 Known BRCAm status was not required but was established retrospectively by germline or tumour testing for patients with appropriate samples available who provided consent (Supplementary Methods).
Assessments Tumour assessments were conducted every 12 weeks until week 60, and every 24 weeks thereafter, until objective disease progression or withdrawal of consent. Response Evaluation Criteria in Solid Tumours (RECIST) data were not collected after the primary DCO (30 June 2010). The primary endpoint of the study was PFS, for which data have been reported previously. 5 OS was a secondary endpoint and we report the final analysis for this outcome here. Patients were monitored for OS with follow-up every 12 weeks after treatment discontinuation. Exploratory analyses of time to first and second subsequent therapy or death (TFST, TSST) were also conducted. Safety and tolerability were assessed throughout the study by recording adverse events (AEs; graded using CTCAE v3. 0), physical examination results, vital signs and laboratory findings.
ACKNOWLEDGEMENTS Medical writing support during the development of this manuscript was provided by  Elin Pyke , MChem from  Mudskipper Business Ltd  and was funded by  AstraZeneca. M. F. is supported by an  NHMRC   Program Grant , ID:  APP1092856. G. has received grants and personal fees from  AstraZeneca, Tesaro and Nucana , grants from  Novartis  and  Aprea , personal fees from  Clovis ,  Roche  and  Foundation One , and has a patent issued ( PCT/US2012/040805 ) and patents pending ( PCT/ GB2013/053202 ,  1409479. 1, 1409476. 7 and 1409478. 3). A. dB. has received personal fees from  Roche ,  AstraZeneca ,  Tesaro, Pharmamar  and  Pfizer. I. V. has received personal fees from  GCI Health, Oncoinvent AS, Roche NV, Genmab A/S, Advaxis Inc. , Morphotek Inc. , F Hoffmann-La Roche Ltd, Cerulean Pharma Inc.
An initial coding of the data relating to the areas in each country was performed, where data extracts describing regulations and PAEHR systems in each area were labeled with a few describing terms. A cross-country analysis was then performed, comparing initial codes from all countries and combining them into themes. The themes were later aggregated into categories of regulatory and PAEHR system approaches as presented in the findings section below. Several rounds of review were conducted in which coauthors examined the interim themes and approaches and provided corrections and feedback. Note that while we base our analyses on vast amounts of documentation, extensive field-level engagement and personal experience from the development in each country, systematic data was lacking in several areas.
Access through a patient portal where patients used a unique static username and password, that was prompted for change three times a year  [62]. US Healthcare provider organizations authenticated patients to establish an account on their portal in several different ways. For example, some required patients to come in person with forms of identification in order to establish an account. Others required patients to answer authentication questions online that were drawn from public records databases of property ownership, car registration, etc. After the patient had been authenticated and an account was established, login usually required a static username and password  [63]. a AU =Australia, NL=Netherlands, NZ=New Zealand, US=United States of America.
Indel analyses identified 258 indels, out of which 191 were found in coding regions and 67 in non-coding regions. Our phylogenetic analyses based on SNP dataset revealed that both serovars are closely related but showed distinct spatial clustering. However, likelihood ratio test of the indel data statistically confirmed the presence of a frameshift mutation within a homopolymeric tract of lic12008 gene (related to LPS biosynthesis) in all the L. interrogans serovar Icterohaemorrhagiae strains but not in the Copenhageni strains. Therefore, this internal indel identified can genetically distinguish L. interrogans serovar Copenhageni from serovar Icterohaemorrhagiae with high discriminatory power. To our knowledge, this is the first study to identify global sequence variations (SNPs and Indels) in L.
Culture, Genomic DNA Extraction, and Sequencing The Leptospira strains were cultured in liquid Ellinghausen-McCullough-Johnson-Harris (EMJH)  (Johnson and Harris, 1967 ) media incubated at 29 • C with moderate shaking at 100 rpm. DNA was extracted from late-log phase cultures using the Maxwell 16 cell DNA purification kit along with the Maxwell DNA extraction system (Promega). The quality and concentration of DNA was measured by spectrophotometry using the NanoDrop system (Thermo Scientific, DE, USA) and by fluorometic assay using the Quanti-iT PicoGreen dsDNA assay kit (Invitrogen). Genomes were sequenced for all 67 strains described in this study and corresponding datasets were recruited for further analyses. Genomic sequencing was done at the J. Craig Venter Institute (JCVI) using an Illumina/Solexa Genome Analyzer II, and at the Yale Center for Genome Analysis (YCGA) using the Illumina HiSeq 2000.
Sequence Analysis Pipeline Reads were mapped to the L. interrogans serogroup Icterohaemorrhagiae serovar Copenhageni L1-130 strain reference genome  (Nascimento et al. , 2004 ) (Accession numbers: NC005823 and NC005824) using Stampy tool  (Lunter and Goodson, 2011). The replicated alignment removal and local realignment were done using Samtools  (Li et al. , 2009). The processed mapping results were further analyzed for SNP calling using Samtools. Called SNPs were filtered to have a quality score cut-off >30. CLC Genomics workbench (CLC Genomics 6. 0. 4) was used to call Indels, and those with coverage lower than 5x were filtered. The Samtools pipeline exhibited better rates of consistency for SNPs calling while CLC was consistent for Indel calling (Figure  1 , Tables  S2, S3 ). In our reference-guided approach, we subsequently analyzed the un-mapped reads and did not detect any plasmids or misplaced contigs.
Bootstrap analysis (1,000 replicates) was used to calculate the statistical support of the tree branches. Bayesian trees were also inferred including the years and country of isolation in the tree construction parameters using BEAST v. 1. 8 package  (Drummond and Rambaut, 2007). For this dataset, we only included the 57 sequences that presented complete data from year and country of isolation (Table  S1 ). The models tested were the strict molecular clock with constant population size prior and the relaxed molecular clock using the constant population size, Bayesian Skyline Plot (BSP), Skyride and exponential growth priors. The parameters for each model were estimated using the Monte Carlo Markov Chain (MCMC) method (50,000,000 generations with sampling every 5,000 generations). The tested models were compared calculating the Bayes Factor (BF).
Using TreeAnnotator v1. 4. 8, included in the BEAST package  (Drummond and Rambaut, 2007) , the maximum clade credibility tree was summarized from the posterior tree distribution after a 50% burn-in, for each dataset  (Drummond and Rambaut, 2007). MacClade was used to identify the frequency of unambiguous changes among various countries from where isolates originated in the tree  (Maddison and Maddison, 1989).
Pipeline for Whole-Genome Mapping In this study, a total of 67 strains were sequenced, out of which 55 strains belonged to L. interrogans serovar Copenhageni and 12 strains belonged to L. interrogans serovar Icterohaemorrhagiae (Table  S1 ). Greater number of L. interrogans serovar Copenhageni sequences were included in this study as this serovar is more prevalent than serovar Icterohaemorrhagiae and has greater number of isolates. All the 67 strains that were included in this study were confirmed by MAT using polyclonal sera for confirmation of Icterohaemorrhagiae serogroup (serogrouping) and monoclonal sera for differentiating Icterohaemorrhagiae and Copenhageni serovars. Serogrouping and serotyping by MAT (data not shown) confirmed the relatedness of the isolates to serogroup Icterohaemorrhagiae, and their identity to serovars Copenhageni or Icterohaemorrhagiae (Table  S1 ).
Stampy and Samtools were used for read mapping and SNP identification, respectively. Indels for both mapping and identification were analyzed using the CLC genome workbench. The pipeline used for identification of SNPs and indels was validated in this study by re-sequencing seven Leptospira isolates. Sequences from each of the seven isolates were analyzed and the selection of the best pipeline was made based on identification of the highest overlap percentage of SNPs and/or indels found in both sequences (Figure  1 , Tables  S2, S3 ). The information related to reads and assembly quality for these sequenced genomes can be found in Table  S4. L. interrogans serovar Copenhageni strain Fiocruz L1-130, sequenced using shotgun technology, was used as the reference genome (Accession numbers: NC005823 and NC005824)  (Nascimento et al.
, 2004). Comparison of genome of L. interrogans serovar Copenhageni strain Fiocruz L1-130 strain re-sequenced using Illumina technology with the previously published genome sequence resulted in identification of 66 SNPs and 62 indels. Of these, 45 SNPs and 46 indels had a distribution frequency of 97% or higher in all the 132 Copenhageni strains sequenced by our group (55 included in this study and 77 from a different study) (data not shown). This higher distribution frequency of SNPs and INDELs in all the above strains might be attributed to the propagation of sequencing errors from the reference L. interrogans Fiocruz L1-130 sequence. In order to avoid those mutations with high frequency from the reference L. interrogans Fiocruz L1-130 sequence we excluded them from our analysis. For this manuscript, we used a reference-guided approach to identify the basic differences between the genomes.
FUNDING Draft genome sequences used in this study are part of a project which was funded with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services under contract number HHSN272200900007C. This project has also been partially funded by the following grants: R01AI052473 (AK), U01AI088752 (AK), R25TW009338 (AK), R01TW009504 (AK), and R01AI121207 (AK). LS was supported by Programa Ciências sem fronteiras Conselho Nacional de Desenvolvimento Cientifico e Tecnológico (CNPq) of Brazil and Brasil Sem Miséria Program of the Coordenação de Aperfeiçoamento de Pessoal de Nível Superios (Capes) of Brazil.
The minor groove of DNA helix acts as a preferred target for small molecules as closer vicinity of strands allows more intimate contact in surface area and therefore, get tightly bind with best tting. 67  The planarity of ancillary N,N-donor ligands are compatible for strong p-p stacking interactions of aromatic moieties present in ligands and also for better match of complexes inside ct-DNA strands. The energetically most favorable docked pose revealed that complexes 1-3 interact in the intercalative sites of DNA helix or at the curve contour in narrow and slightly deeper C-G rich region of minor groove of the targeted DNA (Fig. 11 (a) and S10 †). Docking studies were also performed with tRNA (PDB ID: 6TNA) to corroborate our spectroscopic results. tRNA consists of well dened 3D structure with regions like D arm, T arm, c loop, acceptor stem and anticodon arm which participate directly or indirectly to the target for specic recognition process.