dataesr/scientific-paragraphs-categorization huggingface dataset:
HPLC analysis of saponin extracts Analytical HPLC was performed on a Shimadzu chromatographic system (Kyoto, Japan) at 210 nm. HPLC saponins profiles were carried out on a reversed phase column Symmetry Shield, 250 mm x 4. 7 mm, 5µm (Waters, Milford, MA). All data were acquired and processed with a Shimadzu CLASS-VP (Version 4. 3) HPLC spectrophotometer at two simultaneous wavelengths 210nm and 254nm. Saponins were detected exclusively at 210nm, and 254nm wavelength was used for detection of eventual contaminations like phenolic compounds. The HPLC binary eluting system consisted in two HPLC pumps Shimadzu AT delivering a linear gradient of two solvents in withdrawn ionisation method i. e. with 0. 1% ortho-phosphoric acidic solutions (pH 3): solvent A (sA): acetonitrile (0. 1% ortho-phosphoric acid) and solvent B (sB): 0.
Mass spectrometry MALDI-TOF MS analyses were performed on a Bruker Ultraflex III instrument (BRUKER Daltonik GmbH) equipped with an UV Nd:YAG 200 Hz laser ( = 355 nm). A solution (10 mg/mL) of -cyano-4 hydroxycinnamic acid (Sigma) was prepared in a 1:1 (v/v) 0. 1% TFA/CH3CN (Chromasolv Sigma Aldrich). 10 μL of sample was mixed with 10 μL of matrix. This mixture (1 μL) was spotted on MTP 384 target plate ground steel and air-dried. The data were obtained in positive ions reflectron TOF mode. Each spectrum represents the sum of 1 000 laser shots. External calibration was performed using Polyethylene glycol average M. W. 600 (Aldrich) as calibrant. Results are presented in Figure  S3  and Table  S3.
(Marty et al. 2017)al started in 2014 (by Merck Sharpe and Dohme Corps) was completed at the end of 2016 (Clin-icalTrials. govIdentifier:NCT02137772), and published in 2017(Marty et al. 2017). Letermovir significantly reduced the rate of clinically significant infection at week 24 post graft (end-organ disease or initiation of anti-HCMV pre-emptive therapy based on viremia). And was overall well tolerated. Under the name of Prevymis, letermovir has been recently approved (august 2017) by the US Food and Drug Administration as a new molec-.
(Marty et al. 2017)al started in 2014 (by Merck Sharpe and Dohme Corps) was completed at the end of 2016 (Clin-icalTrials. govIdentifier:NCT02137772), and published in 2017(Marty et al. 2017). Letermovir significantly reduced the rate of clinically significant infection at week 24 post graft (end-organ disease or initiation of anti-HCMV pre-emptive therapy based on viremia). And was overall well tolerated. Under the name of Prevymis, letermovir has been recently approved (august 2017) by the US Food and Drug Administration as a new molec- ular entity for prophylaxis of cytomegalovirus infection and disease in adult CMV-seropositive recipients of an allogeneic hematopoietic stem cell transplant (www. accessdata. fda. gov, Reference ID 4179078). As transplant recipients receive antivirals coadministered with cyclosporine A (CsA) or tacrolimus (TAC) as immunosuppressants, clinical trials investigated the poten- tial for letermovir-immunosuppressant interactions.
The MIC/MBC determinations reveal that more peptide is required for bacterial death when higher bacterial inocula are used. This difference is significant for E. coli, for a Theoretical molecular mass was calculated using GPMAW version 8. 10. b Experimental molecular mass was determined from the MS spectra shown in Fig. S1b. c Peptide purity was estimated by peak integration of the analytical HPLC chromatograms shown in Fig. S1a. d ACN gradient over 15 min used to run the analytical HPLC. Range indicates the initial and final ACN concentrations. e Percentage of ACN corresponding to the eluted peptide, calculated from the gradient used and the retention time. f Protein Data Bank accession code of Ctn: 2MWT.
Time-resolved peptide uptake and bacterial death Changes in membrane permeabilization and peptide uptake were monitored by a time-resolved flow cytometry assay, which allows a more accurate study of the kinetics of peptide effect, compared with kinetic studies based on end-point sampling. We studied the membrane permeabilization of E. coli using SYTOX Green dye right after Ctn or Ctn(15-34) addition, monitoring the changes from negative to positive gates for 90 min. Fig. 3 (a  and b ) shows time-course results and negative and positive controls (for the whole acquisition, see Movies S1a and S1b for Ctn and Ctn(15-34), respectively). As detailed under "Experimental procedures," data from the FCA histograms were used to generate the kinetic curves on Fig. 3c. Data were fitted using the two-state kinetic model described previously for other AMPs  (34) , assuming that peptide-bacteria interaction consists of an initial binding step, followed by permeabilization of the membrane.
Membrane permeabilization induced by RhB-labeled peptides Samples for FCA were prepared as described above. Data were acquired on a BD FACSAria III cell sorter (BD Biosciences) using blue (488-nm) and yellow-green (561-nm) lasers and emission filters BP530/30 (LP505) and BP586/15 to detect SYTOX Green and RhB, respectively. 5000 events corresponding to bacterial population as previously defined by forward scatter and side scatter were recorded. Experiments were performed in triplicate.
In the normal confocal mode, ϫ0. 6 zoom images were recorded at 1024 ϫ 1024 resolution. In the Airyscan superresolution mode, 5. 5ϫ zoom was applied to select one single bacteria cell, and the optimal resolution was selected. ZEN software was used for image acquisition and Airyscan image processing. Fiji software was used for background subtraction and brightness and contrast adjust (identically for compared image sets). At least 12 total images were acquired in three independent replicates.
This work was supported by  Agence Nationale de la Recherche  Grant  ANR-12-PDOC-0028 -Project  Apicolipid; the  Centre National de la Recherche Scientifique Atip-Avenir  and  Finovi  programs; and the  Laboratoire d'Excellence Parafrap Grant   ANR-11-LABX-0024. C. Y. B. is a  Centre National de la Recherche Scientifique Atip-Avenir Fellow.
Partnerships between researchers and policymakers can improve uptake and integration of scientific evidence. This article describes the research-policy partnership between the international epidemiology Databases to evaluate AiDS (ieDeA) (www. iedea. org) and the world Health Organization (wHO), which was established in 2014. ieDeA is an international research consortium, which analyses data on almost 2 million people living with Hiv under care in routine settings in 46 countries in Asia-Pacific, the Caribbean, Central and South America, North America and sub-Saharan Africa. Five multiregional analyses were identified to inform the wHO on progress towards the second and third 90s of the 90-90-90 targets in adults and children: (i) trends in CD4 cell counts at the start of antiretroviral therapy (ART); (ii) delays from enrolment in Hiv care to ART initiation; (iii) the impact of ART guideline changes; (iv) retention in care, mortality and loss to follow-up; and (v) viral suppression within the first 3 years after initiating ART.
Results from these analyses were contributed to the 2015 and 2016 wHO global Hiv progress reports, will contribute to the 2018 report, and were published in academic journals. The partnership has been mutually beneficial: discussion of wHO policy agendas led to more policy-framed, relevant and timely ieDeA research, and the collaboration provided the wHO with timely access to the latest data from ieDeA, as it was shared prior to peer-review publication.
This article summarises the process, output and challenges of a research-policy partnership between the international epidemiology Databases to evaluate AiDS (ieDeA) and the wHO that aims to formalise and facilitate uptake and integration of ieDeA scientific evidence into wHO ART progress reporting and Hiv health policy development. The International epidemiology Databases to Evaluate AIDS (IeDEA) ieDeA (www. iedea. org) is an international research consortium of Hiv cohorts funded by the National institutes of Health (NiH) since 2006  [18] [19] [20]. ieDeA pools existing clinical and epidemiological data on people living with Hiv under care in routine settings as a cost-effective way of generating large data sets to address high priority and evolving research questions in Hiv/ AiDS treatment and care.
The seven regions included in ieDeA are: Asia-Pacific; the Caribbean, Central and South America (CCASA); North America; and four regions in Africa (Figure  1 ). Across these regions, ieDeA has individual-level data on over 1. 7 million patients from over 480 clinic and research centres in and 90% of all people receiving ART are virally suppressed by 2020  [27]. These fast-track targets aimed to improve the Hiv cascade of care with the goal of ending the AiDS epidemic as a public health threat by 2030  [27]. in the following year, wHO released the 'treat all' guideline update, recommending immediate ART for all people living with Hiv, eliminating prerequisites for initiating treatment  [28]. The collaboration commenced with a face-to-face meeting at the wHO headquarters in Geneva, Switzerland in November 2014, where four members of the wHO Department of Hiv/AiDS and four investigators of the ieDeA Southern Africa team based in Bern, Switzerland, discussed potential collaborative work.
Four video conference calls were subsequently held in early February 2015 to discuss analyses that the ieDeA consortium could undertake to support the wHO 2015 global Hiv progress report. each call had between 10 and 12 participants from the seven ieDeA regions, the NiH-funding institutions and the wHO. Later that month, during the ieDeA Scientific Symposium at the Conference on Retroviruses and Opportunistic infections (CROi), attended by more than 20 ieDeA investigators representing every ieDeA region, the ieDeA consortium agreed to undertake this collaboration with the wHO, and identified five core multiregional cascade analyses and the teams that would undertake them. These cascade analyses aimed to inform the wHO on progress towards the 90-90-90 targets, guideline implementation and trends in the epidemic, using routinely collected ieDeA programme data (Table  1 ).
ieDeA-wHO analyses Cohorts cannot provide information on the number of people living with Hiv or the number who know their status in their settings, so the collaboration is unable to assess the first 90 (percentage knowing their status). The ieDeA collaboration can, however, examine how quickly patients are started on ART after linkage to care and enrolment at their clinics, and how many of those who start ART have stopped treatment (the second 90 target), while those cohorts that collect routine viral load data can also assess the third 90 target. with more than 15 years of ieDeA collects routine data from both urban and rural settings, in primary through tertiary care facilities, and from small private clinics to large programmes run by national health systems. Patient information, clinic visit history, laboratory measurements, medications and clinical outcomes are some of the data collected by ieDeA regional cohorts.
The IeDEA-WHO collaboration The ieDeA-wHO collaboration was launched at the end of 2014, after more than a decade of ad hoc work between ieDeA and the wHO. The wHO was seeking to formally collaborate with ieDeA so that up-to-date ieDeA data and analyses could contribute in a predictable and sustainable way to wHO annual global Hiv progress reporting and guideline development. The wHO wanted to rapidly assess implementation of new Hiv policy recommendations, and identify and characterise gaps in the response, which randomised control trials and observational studies based on outdated data cannot address. The ieDeA Southern Africa region was awarded an NiH grant supplement to fund a part-time project manager to initiate, plan and develop a formal collaboration between the ieDeA consortium and the wHO.
At that time, UNAiDS had just released ambitious 90-90-90 fast-track targets: 90% of all people living with Hiv know their status, 90% of people diagnosed with Hiv are on sustained ART, Analysis of delays from enrolment in Hiv care to ART initiation and the influence and impact of ART guideline changes among adults and children  [32, 33]  All seven ieDeA regions Analysis of retention in care, mortality and loss to follow-up among Hiv-infected children and adults on ART  [34]  All seven ieDeA regions Third 90: 90% of all people receiving ART are virally suppressed Analysis of routine viral load data to assess viral suppression among adults and children within the first 3 years after initiating ART  [35]  All seven ieDeA regions months from data collection. Over the years, these analyses have supported three wHO global progress reports.
Project organisation and management More than 65 ieDeA regional investigators across the seven ieDeA regions, 10 representatives of the NiH funding institutions, and nine wHO staff members have been involved with this collaboration since its inception. The collaboration project manager liaised between the ieDeA network and the wHO, and provided updates on work and progress in monthly ieDeA working group conference calls and by email. ieDeA held project debriefs to discuss and evaluate the process and work of the collaboration following publication of the annual wHO progress reports. ieDeA multiregional data are only available after review and approval of a concept proposal by the ieDeA executive Committee. This committee is composed of principal investigators from the seven ieDeA regions and representatives of the NiH funding institutions, including the National institute of Allergy and infectious Diseases, the eunice Kennedy Shriver institute on Child Health and Human Development, the National Cancer institute, the National institute of Mental Health and the National institute on Drug Abuse.
For each iteration of the above analyses, ieDeA, in consultation with the wHO, drafted new concept proposals that were reviewed by the ieDeA Strategic Data working Group (wG) prior to submission to the executive Committee. The Strategic Data wG holds monthly conference calls to promote and guide ieDeA multiregional research conducted in collaboration with external partners, and consists of representatives from each ieDeA region and programme staff from the NiH and the wHO. Following executive Committee approval, the concept proposal teams worked with the ieDeA Data Harmonization wG, comprised of ieDeA regional data managers and analysts, to clarify data elements and organise data transfer. To help navigate, streamline and facilitate ieDeA procedures, a timeline was drafted, outlining deliverables and deadlines to ensure research occurred in a timely manner and aligned with the timeline for the development of annual wHO Progress Reports.
ieDeA also undertook efforts to synchronise and increase the frequency of data collection to ensure that the most up-to-date data were available for these purposes. longitudinal data and accompanying facility information, ieDeA can monitor and examine temporal trends in patient care uptake and outcomes, and the impact of Hiv guideline changes. Progress towards the second 90 target was evaluated by two multiregional ieDeA-wHO analyses that focused on the pre-ART care cascade, and assessed delays from linkage to and enrolment in Hiv care to ART initiation and the influence and impact of ART guideline changes among adults and children, separately  [32, 33]. The ieDeA west Africa data centre undertook the multiregional analysis that focused on children, and the ieDeA Central Africa data centre performed the multiregional analysis on adults.
These analyses were undertaken in 2015, 2016 and 2017. The ieDeA Central Africa team additionally collaborated with the wHO to collect historical data on country-level ART guideline expansions by searching the internet for national ART policies and contacting ieDeA and wHO in-country experts. A third ieDeA-wHO analysis described retention in care, mortality and loss to follow-up among children and adults living with Hiv on ART, and compared outcomes under different ART eligibility guidelines to examine whether people who start ART remain on ART  [34]. This multiregional analysis was performed at the ieDeA Southern Africa data centre in 2015, 2016 and 2017. A fourth ieDeA-wHO analysis assessed outcomes in younger (10-14 years of age) and older (15-19 years of age) adolescents to provide insights into long-term retention for the mixed population of perinatally and behaviourally infected youth.
The ieDeA Asia-Pacific data centre undertook this analysis in 2016. The last core multiregional analysis of the collaboration used ieDeA routine viral load data to assess viral suppression (<1000 copies/mL) among adults and children within the first 3 years after initiating ART  [35]. This multiregional analysis was undertaken in 2015 and 2017 by the ieDeA Asia-Pacific data centre. Additionally, one analysis took advantage of South Africa's National Population Register, with nearly complete enumeration of deaths and extensive long-term follow-up data of patients on ART, to assess advances in life expectancy over time  [36]. The ieDeA Southern Africa data centre performed this analysis in 2015 using data from South African cohorts. Since the ieDeA-wHO collaboration began, ieDeA has produced 12 multiregional analyses and one region-specific analysis -an average of four analyses per year using newly reported ieDeA data.
Reports and publications The results from the ieDeA-wHO collaboration analyses were presented in two wHO reports and several academic publications. The Global health sector response to HIV, 2000-2015: focus on innovations in Africa was the 2015 wHO global Hiv progress report released in November of that year  [3]. The report relied on evidence produced by the ieDeA-wHO collaboration to highlight gaps between Hiv diagnosis and treatment initiation. evidence on over 800,000 adults from 10 African countries enrolled in ieDeA clinics from 2004 to 2014 showed that about 22% of adults were lost to follow-up before initiating ART. Despite this shortfall, ieDeA data indicated a steady shift towards earlier enrolment in Hiv care as illustrated in a graph showing increasing median CD4 cell count at enrolment in Hiv care across ieDeA programmes from 2004 to 2014.
Despite these challenges, the report found people have been starting ART earlier and at higher CD4 cell counts, as illustrated in a figure showing increasing median CD4 cell count at ART initiation at ieDeA clinics up to 2015 (Figure  3 ). This report also highlighted another collaboration analysis as evidence that a high level of viral suppression can be achieved, even in resource-limited settings. At present, the collaboration is undertaking four multiregional cascade analysis updates to assess the impact of recent guideline changes and progress towards the 90-90-90 targets across all age groups, to support the 2018 wHO global progress report that is currently under development for release at the end of 2018. Beyond supporting wHO, these analyses have also generated 14 abstracts presented at international research conferences, including the international workshop on Hiv and Hepatitis Observational Databases (iwHOD), CROi, the international AiDS Society conferences, and Australian Hiv and AiDS conferences.
Discussion Over the past 4 years, ieDeA has produced 13 analyses based on ieDeA multiregional cohort data to support wHO Hiv guideline development and ART progress reporting. evidence from ieDeA contributed to the 2015 and 2016 wHO global Hiv progress reports and two wHO Hiv guideline updates. Research evidence from these analyses also informed audiences outside of the wHO. Fourteen oral abstract presentations and posters were presented at international Hiv conferences and workshops. The five core analyses and the one regional analysis have also resulted in five peer-reviewed publications  [32] [33] [34] [35] [36]. The ieDeA-wHO collaboration is an example of a research-policy partnership overcoming barriers that often hinder the rapid uptake and integration of research evidence into policy development  [12, 14, 16, 38].
increased interaction and regular communication strengthened links between ieDeA and wHO, as each became more aware of how ieDeA could be a resource to wHO and vice versa. Opportunities for discussion of upcoming wHO policy agendas led to more policy-framed, relevant and timely ieDeA research. The science has also been strengthened through this opportunity for the wHO and ieDeA research teams to communicate on the strengths and weaknesses of reporting indicators. The collaboration also provided the wHO with more timely access to the latest ieDeA scientific evidence, as it was shared with them prior to peer-review publication. efforts to synchronise and accelerate data extraction in ieDeA resulted in more timely and up-to-date data that benefited the collaboration work as well as other multiregional research.
The collaboration timelines ensured ieDeA procedures were navigated efficiently, allowing analyses to be completed annually. This research-policy partnership provided a unique opportunity for the wHO to monitor current implementation progress of their action-oriented guidelines and for ieDeA to produce more innovative policy-relevant observational research evidence. Although ieDeA successfully produced and shared multiregional analyses with wHO, combining large volumes of data from such a wide range of settings on tight timelines can present a number of challenges. issues of missing data on key variables, and varying definitions and data collection protocols, led to a duplication of time-consuming data cleaning efforts undertaken simultaneously by research teams. inconsistent data distribution and a large variability in the volume of data across regions, due to the uneven burden of disease and temporal trends, limited the ability to provide region-specific and age-specific stratified estimates, complicating the interpretation of findings.
Service delivery models, clinical protocols, standards of care, monitoring schedules and efforts in place to trace patients lost to follow-up also vary widely. The tight timeline dictated by the wHO publication schedule increased and concentrated the workload of ieDeA regional data managers responsible for preparing and transferring data for up to five separate research proposals requesting varying data elements and eligibility criteria within the same timeframe, and alongside other regional and multiregional data requests, each year. However, engagement with wHO also highlighted areas where ieDeA and its data workflows could be improved or made more efficient. Data and structural challenges experienced in this collaboration with wHO propelled ieDeA to develop and implement improvements to expand and increase data collection and analytic capacity.
The Strategic Data wG was established in the second year of the collaboration to facilitate regular dialogue between the ieDeA network and the wHO through monthly teleconference calls. Data harmonisation improvements were undertaken to ensure ieDeA data standards were up-to-date and met current multiregional research needs. The ieDeA data exchange standard (www. ieDeADeS. org) was translated from paper format to an online research electronic data capture (ReDcap) database to simplify, coordinate and accelerate updates across multiple platforms, and enable faster and better data exchange and collaborative research  [39]. in response to the growing number and frequency of multiregional concept proposals, ieDeA developed an online review hub to simplify, streamline and expedite the concept proposal review and approval process for multiregional research.