dataesr/scientific-paragraphs-categorization huggingface dataset:
Our study showed that the risk of death in patients diagnosed DM tended to be higher after 4 years of follow-up, a finding similar to that reported by a previous study in Thailand  [34]. Although causes of death were not available, we hypothesized that the increasing risk of death with DM may have been related to cardiovascular and renal complications as well as HIV infection itself. A limitation of our study is that the NAP database has been primarily designed for overall monitoring of the program with missing data not systematically tracked as in clinical studies. Importantly, the NAP database represents a unique source of information that likely reflects the actual DM burden in the HIV infected population. Also, the lack of systematic FPG assessments in some patients may have led to an underestimation of DM incidence.
Acknowledgments We would like to thank the  NHSO, Thailand  for providing the data, in particular  Winai Sawasdivorn ,  Jadej Thammatacharee ,  Yongyuth Pongsupap ,  Yolsilp Suchonwanich ,  Sinchai Tawwuttanakidgul ,  Suchada Chaivooth ,  Chirod Narkpaichit ,  Artit Pusamang ,  Sumitra Daengprasert ,  Sumalee Hiranmongkholkul ,  Traithep Fongthong ,  Kanjana Sirigomon , and  Jutatip Thungthong.
Toxocara cati Table  4  presents the risk factors used for the T. cati model and their effects on T. cati infection status. The likelihood of T. cati infection was higher (B = 0. 98, df = 1, P < 0. 0001) for cats living outdoors in comparison to those living indoors (c. 2. 7 times, 95% CI: 1. 7-4. 1), although no significant difference was noted between owned and stray cats. Similarly, a 1. 3-fold higher (95% CI: 1-1. 7) probability for T. cati infection was recorded for female cats, which, though, was not statistically significant (B = -0. 25, df = 1, P = 0. 081). Regarding co-infections, cats infected with Cystoisospora spp. were 1. 4 times (95% CI: 1-1. 9) more likely to be infected with T. cati when compared to non-infected ones (B = -0. 31, df = 1, P = 0. 086). The model provided a good fit to the data with the H-L test being insignificant (χ 2 = 1.
5 96. 6 96. 3 Giardia spp. infection status Uninfected 1126 0 100 907 0 100 219 0 100 Infected 26 0 0 18 0 0 8 0 0 Accuracy rate 97. 7 98. 1 96. 5 rate of the full dataset, the training (80%) and the holdout sample (20%) of Toxocara cati, Cystoisospora spp. , Ancylostomatidae, Aelurostrongylus abstrusus and Giardia spp. models a Infection status refers to Toxocara cati, Cystoisospora spp. , Ancylostomatidae, Aelurostrongylus abstrusus and Giardia spp. predicted infection status in accordance to the observed infection status of the aforementioned parasite species equal to 0. 65 (P < 0. 0001). Cox and Snell R 2 -value and Nagelkerke R 2 -value were 0. 039 and 0. 066, respectively.
FUNDING  ANR-DFG  Joint Grant [HTRNAMod to Y. M. , M. H. ;  ANR-13-ISV8-0001/HE 3397/8-1 ];  DFG Grants  [ DA 592/5-1  to A. D. , HE  3397/9-1 ,  HE 3397/ 13-1  ( SPP1784 ) to M. H. ]. Funding for open access charge:  Johannes Gutenberg-University.
ACKNOWLEDGMENTS The authors thank  Rahel Klein ,  Ulrike Herian ,  Uta Haselmann  and  Jutta Mohr  for excellent technical assistance and  Vibor Laketa  for microscopy support. We are grateful to the  Electron Microscopy Core Facility of the University of Heidelberg  for providing access to their equipment and thanks to  Dr. Charlotta Funaya  and  Dr. Stefan Hillmer  for technical support in EM work. A plasmid encoding TLR3 was a kind gift from  T. Espevik ,  NTNU, Trondheim, Norway. In addition, we thank  Daniel Lamarre  for helpful discussions.
Expression vectors Cloning of nef alleles into the bi-cistronic CMV promoter-based pCG expression vector coexpressing the enhanced green fluorescent protein (eGFP) or blue fluorescent protein (BFP) was described previously  [6, 67]. In brief, nef genes were amplified by PCR with flanking primers introducing XbaI and MluI restriction sites for cloning into the pCG IRES eGFP or BFP vectors. Mutant Nef variants (SIVcol Y86F, Y87F Nef) were generated by mutating TAT (Tyr86) to TTC (Phe) and TAC (Tyr87) to TTC (Phe). Sequence of tetherin from Colobus guereza kikuyuensis was obtained from the public database and synthesized. Internal Mlul restriction site was removed without changing the protein amino acid sequence (GCG to GCC). Colobus tetherin was cloned into pCG expression vector co-expressing BFP as described  [60]  and confirmed by sequence analysis.
qRT-PCR PBMCs were obtained from the same donors as used in the PBMC kinetic described above. Cells were cultured for 3 days in RPMI 1640 medium with 10% fetal calf serum and antibiotics, containing either phytohemagglutinin (2 μg/ml), 10 ng/ml interleukin-2 (IL-2) or both. RNA was isolated using RNeasy Plus Mini Kit (Qiagen 74136) and reverse transcribed with Prime Script RT reagent kit (Takara #RR037A). Gene expression was measured using TaqMan Fast Universal PCR Master Mix (ThermoFisher #4352042) and the following TaqMan probes: SER-INC5 (ThermoFisher #Hs00968169_m1) and as a normalization control, GAPDH (Thermo-Fisher #Hs99999905_m1). Ct data was processed relative to the GAPDH control and further normalized to control cells cultured in the absence of IL-2 and PHA from the same donor.
Acknowledgments We thank  Kerstin Regensburger  for technical assistance,  Massimo Pizzato  and  Heinrich Go  ¨ttlinger for reagents, and  Thomas Hoffmann  and  Johannes Do ¨scher  ( HNO, University Clinic Ulm ) for providing tonsils. TZM-bl cells were obtained through the  NIH AIDS Reagent Program, Division of AIDS, NIAID, NIH : TZM-bl from  Dr. John C. Kappes ,  Dr. Xiaoyun Wu  and  Tranzyme Inc.
Cryo-electron microscopy of HIV-1 virions Cell culture supernatants containing HIV particles were fixed in 8% paraformaldehyde (EM grade) solubilized in a 4% cacodylate buffer. Virus particles were pelleted by ultracentrifugation in an SW32Ti rotor (Beckman) for 3 h at 17,000 rpm together with 10 l of colloidal gold particles (Aurion, GaR 10) to better localize the pellet. Virus pellets were suspended in 50 l of 50 mM Tris, pH 8, and 2. 5 l was applied to Quantifoil R2/2 holey carbon grids, which were then plunged frozen into liquid ethane using a Vitrobot instrument (Thermo Fisher Scientific). For data acquisition, grids were transferred to the Polara electron microscope equipped with a Falcon I camera, and images were acquired at 300-kV acceleration voltage under low dose conditions at Ϫ6 m defocus.
Structures and structure factors have been deposited in the PDB database with codes 4LH4 (IN CCD TT) (15), 5OI3 (IN CCD AA), 5OI2 (IN CCD TT ϩ MUT-A), 5OI5 (IN CCD TT ϩ MUT-A03), 5OI8 (IN CCD AA ϩ MUT-A), and 5OIA (IN CCD AA ϩ MUT-A03).
Acknowledgments-We thank  Stephane Huguet  for support;  Juliette Nguyen ,  Roxane Beauvoir , and  Elodie Drocourt  for assistance in virology; Frederic  Le Strat  for fruitful discussions; and the  National Institutes of Health  AIDS research repository for primary isolates. We thank  Nicolas Le  ´vy and  Vincent Olieric  for help in X-ray data collection on beamline X06DA (PXIII) at the  Swiss Light Source ,  Paul Scherrer Institute, Villigen, Switzerland. We thank  Alastair McEwen  for help in X-ray data collection at the home source.
This work was supported in part by  Biodim Mutabilis  under Authorization Number  DUO 2145 , assigned by the  French Ministry of Research  for work with genetically modified organisms, by Grants  EU FP7  (to Biodim,  S. Emiliani , A. S. , and A. Z. ) under the  HIVINNOV  Consortium, Grant Agreement 305137, and by  Eurostars Grant ResistAids  (to Biodim), Grant Agreement E!10239. 3Supported by the  French National Research Agency against AIDS (ANRS)  and SIDACTION. 4Supported by  French Infrastructure for Integrated Structural Biology (FRISBI)  Grant  ANR-10-INSB-05-01  and by Instruct-ERIC. 5 Supported by the  French National Association for Research and Technology (ANRT).
Overview This MAIC analysis was conducted according to the National Institute for Health and Care Excellence (NICE) Technical Support Document (TSD) guidance  [21]  for a robust, population-adjusted ITC. This required the identification of randomised controlled studies of IL-5Rα/anti-IL-5 treatments with similar study methods. Studies were identified through systematic review. We then applied stringent requirements for MAIC analysis, which required narrowing the selection of trials, as described below. To perform matching of the benralizumab population to the comparator treatment populations, we used several steps to identify variables that were known to modify treatment effects. Data from patients in the benralizumab population were then weighted to reflect the treatment-effect-modifying characteristics in the comparator populations.
Study selection and data extraction Further details on the methods for the systematic review are detailed in appendix 1. The systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement  [22] , and the requirements of health technology appraisal organisations in the UK, Germany, France and the USA. MEDLINE, EMBASE, MEDLINE In-Process and CENTRAL databases were searched using a combination of medical subject headings and free-text terms to identify English-language articles of relevant studies of biologics in moderate to severe uncontrolled asthma. Searches were conducted from database inception to August 2016 (search date). Conference abstracts were included and identified via EMBASE or hand searching of the relevant conference website.
All studies included the following outcomes, which were chosen to reflect their clinical significance in severe asthma, inclusion as primary endpoints in severe asthma trials and availability of data across trials: annual rate of clinically significant exacerbations, annual rate of exacerbations requiring emergency department (ED) visit or hospitalisation, and pre-bronchodilator forced expiratory volume in 1 s (FEV1). Because definitions of exacerbation might differ, we included only trials in which the definition of exacerbation included worsening of asthma symptoms leading to use of systemic corticosteroids and an urgent care/ED visit or hospitalisation. Citations identified through literature searches were screened for inclusion on the following prospectively defined criteria: randomised controlled trials comparing IL-5Rα/anti-IL-5 treatments with placebo for patients with severe, uncontrolled asthma receiving medium-or high-dosage ICS plus an additional controller medication.
Data analysis Exacerbation rate outcomes were estimated as rate ratios (RR) for monoclonal antibody treatments versus placebo. Change in FEV1 was estimated as the mean difference between monoclonal antibody treatments and placebo. Studies were evaluated in detail for differences in study methods, presence of potential treatment-effect-modifying patient characteristics, and availability of variables and outcomes of interest in the treatment comparisons. Variables that we believed made findings uninterpretable because of between-trial variability were identified through elicitation of opinion from asthma experts, a literature review, and univariate and multivariate analyses of  SIROCCO [9]  and CALIMA data  [11]. Eligibility criteria were then refined to increase the face validity of comparisons.
Data for benralizumab were obtained by pooling the individual patient data from the SIROCCO and CALIMA trials ( patients who received FP ⩾880 µg•day -1 for the mepolizumab comparison and patients who received FP ⩾500 µg•day -1 for the reslizumab comparison). Aggregate data for mepolizumab were pooled from the clinical study reports for MENSA and DREAM (mepolizumab 75-mg data pooled from MENSA and DREAM; mepolizumab 100-mg data from MENSA). Aggregate results for reslizumab came from publications of Study 3082 and Study 3083  [10]. Study details for benralizumab, mepolizumab and reslizumab are presented in appendix 2, table  S4.
Benralizumab versus reslizumab comparison For the benralizumab versus reslizumab comparison, the following variables were selected for matching: mean baseline eosinophil count, mean number of exacerbations in the previous 12 months, sex and maintenance OCS use (table  5 ). Matching the benralizumab SIROCCO/CALIMA dataset to the reslizumab population resulted in a 99% reduction in the ESS, from 1668 to 20 (table  6 ), indicating very little overlap in the treatment characteristics of the patient populations. The small ESS of 20 patients was not sufficient to support a robust MAIC between benralizumab and reslizumab.
When methods differ between studies, the placebo effect size can also differ. For example, the placebo group's annual exacerbation event rate was greater in the pooled MENSA/DREAM data than in the pooled SIROCCO/CALIMA data (2. 0 and 1. 27 events per year, respectively). This difference might have been caused by procedural differences between studies, such as permitted concomitant treatments. However, when the SIROCCO/CALIMA data were matched to the MENSA/DREAM patient population characteristics in our MAIC analysis, the placebo group's annual exacerbation event rate in SIROCCO/CALIMA increased from 1. 27 to 1. 63 (appendix 2), suggesting that at least part of this difference in the placebo effects for benralizumab versus mepolizumab was because of patient population differences. Inspection of patient baseline characteristics in each pooled dataset (table 1) also suggests that patients taking mepolizumab had somewhat more severe asthma than patients taking benralizumab, as indicated by differences in baseline eosinophil count, prior exacerbations and the percentage of patients using OCS at baseline.
Acknowledgements: The authors thank  Lance Brannman ,  Sarang Rastogi  and  Ian Hirsch  of  AstraZeneca  for conceptual input in the early stages of this work and  Pragya Shukla  of  PARAXEL International  for contributions to the design and conduct of the analyses. Editorial support was provided by  Ellen Stoltzfus  and  Francis John Golder  of  JK Associates, Inc. , and  Michael A. Nissen  of  AstraZeneca. This support was funded by  AstraZeneca.
2A peptide mediates a co-translational cleavage at its own C-terminus and is proposed to cause the ribosome to skip the synthesis of a specific peptide bond, producing a discontinuity in the peptide backbone  [21]. For some proteins, wild-type sequence (TB Database, www. tbdb. org) has been conserved, deleted or mutated. The first fusion Rv2626/T2A/Ag85B was constituted by the full-length Rv2626 (full length wild type sequence) protein followed by a GSG linker and fused to the T2A peptide from Thosea asigna virus and the residues 33 to 325 of Ag85B polypeptide (wild type sequence without a part of signal peptide). The second fusion, CFP10/ESAT6, was constituted by the full-length CFP10 protein fused to the full-length ESAT6 protein separated by a linker composed of residues 149 to 162 of the Mtb protein Rv1827.
Immunogenicity of MVATG18598 Although IFNγ is not recognized per se as being a correlate of protection in TB infection, it is believed to be an important contributor to the control of mycobacterial replication  [32]. ELI-Spot analysis was performed one week after naïve mouse immunization to investigate the specific IFNγ response induced by the MVATG18598. Immune responses specific to each expressed Mtb antigen were evaluated in two different inbred mouse strains, BALB/c (H-2 d ) and C57BL/6 (H-2 b ). Regardless of the mouse strain, a typically robust IFNγ response specific to the MVA was detected in the MVATGN33. 1 control group as well as the MVATG18598vaccinated group (>800 spots/10 6 cells, data not shown). In BALB/c mice, Ag-specific IFNγ-producing T cells were detected for 6 out of the 10 Ag expressed by MVATG18598 (Fig  2A ).
4 (130 spots/10 6 cells) and, in contrast to observations in BALB/c mice, for Rv0287 (173 spots/10 6 cells). To assess which functional T cell subsets contribute to the MVATG18598-induced response, we investigated co-expression of the Th1 cytokines, IL2 and TNFαin addition to We investigated whether the T cells elicited following MVATG18598 vaccination display cytotoxicity in vivo. In vivo cytotoxic T cell (CTL) assays were performed in hybrid CB6F1 mice immunized twice with vaccine using target cells pulsed with pools of antigen-specific peptides. Mice immunized with either the MVATG18598 or the control vector generated a strong CTL killing response to the MVA peptide-pulsed targets (80-90%, data not shown). Interestingly, MVATG18598-immunized mice developed a CTL killing response specific to 8 out of 10 antigens covering the different phases of the disease and notably commonly referred to active, latency and resuscitation (Fig  2C ).
1 after antibiotic therapy (3-4 log 10 ), higher amounts of antibodies were induced in mice vaccinated with MVATG18598 (4-6 log 10 ) regardless of the positioning and route of vaccination. Among the described latent antigens, Rv2626 is the only antigen for which antibody response was measured, higher levels of antibodies being detected in MVATG18598 vaccinated mice, regardless of kinetics and routes of vaccination. No antibodies directed against RpfB-RpfD were detected. Overall, MVATG18598 vaccination led to a sustained significant higher level of antibodies which were poorly or not induced in control mice. Injection route or vaccine positioning did not impact antibody detection. No correlation between CFU counts and antibody levels was demonstrated using Spearman correlation test (data not shown).
We evaluated MVATG18598 therapeutic activity in this model using the optimal route and schedule of administration identified previously. Global protocol scheme is outlined in Fig 5A. Mice were infected with a low dose aerosol and treated with an isoniazid and rifapentine regimen from Week 6 to 16 post-infection. MVATG18598 was given through subcutaneous route 3 times at 3-week intervals starting at Week 9 post-infection. As a negative control, a subset of infected mice was vaccinated with the empty MVATGN33. 1 virus. Bacterial burden in vaccinated mice was assessed 7 weeks after therapy completion (Week 23) and compared to the control group treated with antibiotics only. Two independent experiments using 12 mice per group were run. Unexpectedly, technical issues were encountered during the in vitro mycobacterial culture phase resulting in incomplete CFU data for some animals.
Only results of exploitable individual mice data from the two pooled experiments were used for statistical comparison between groups. A total of 16, 7 and 10 mice for the PH, MVATGN33. 1 and MVATG18598 groups, respectively, were counted (Fig 5B  and Table 3 ). All mice relapsed, as expected. Lung CFU counts reached the expected level in the antibiotic control group (4. 3 ± 0. 1 log 10 ). While vaccination with MVATGN33. 1 did not impact bacterial burden, a statistically significant reduction in CFU count was measured in mice vaccinated with MVATG18598 (0. 7 ± 0. 3 log 10 reduction, Fig 5B and Table  3 ). This result is in agreement with the impact of MVATG18598 vaccination on CFU counts in BALB/c mice. We monitored specific immune responses in vaccinated C57BL/6 mice at the end of each independently-run experiment.
1 (12/24 mice, 0. 8 log 10 ) suggesting that the MVA virus might have boosted specific antibody response through innate immunity. Of note, Rv2626-specific antibodies were significantly measured in MVATG18598-vaccinated C57BL/6 mice (1. 5 log 10 ) in comparison with control groups. No antibodies specific of Rv3407, Rv1813 and RpfB-RpfD was detected except sporadically. Although high antigen-specific T and B cell responses were mounted in vaccinated mice, no correlation could be found with the lung bacterial burden (data not shown). Overall, the protective efficacy of MVATG18598 against Mtb regrowth (approx. 1 log 10 CFU mean reduction) was confirmed using two post-exposure mouse models. In both models, MVATG18598 vaccination triggered a sustained Ag-specific memory response (T and B cells) directed at multiple antigens.
Acknowledgments The authors thank all employees of both  Plateau de Biologie Experimentale de la Souris in Lyon  and the animal facility at  Johns Hopkins University Center for Tuberculosis Research in Baltimore. We are thankful to  Dominique Villeval  for the purification of the MVA vaccines. Our special acknowledgment to  Mr Alain Me  ´rieux for his constant support through the performance of the  MVA-TB-based program.
The project described was supported in part by  Award Number   R01-AI098911  from the  National Institute of Allergy and Infectious Diseases  (http://www. niaid. nih. gov). The content is solely the responsibility of the authors and does not necessarily represent the official views of the  National Institute of Allergy and Infectious Diseases  or the  National Institutes of Health. This project has received funding from the  European Union 's  Horizon 2020 research and innovation programme  under grant agreement No  643381  (https://ec. europa. eu/programmes/horizon2020). The content is solely the responsibility of the authors and does not necessarily represent the official views of the Commission. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Variables and definitions Data recorded from medical files included WHZ or BMIZ scores, puberty onset (defined as a child reaching stage 2 of the Tanner classification  [23] ), WHO stage at ART initiation and therapeutic history, CD4 cell counts and viral load (undetectable defined as HIV RNA < 40 copies per milliliter), total cholesterol, LDL cholesterol and triglycerides. Dyslipidemia was defined as total cholesterol and/or isolated HDL and/or triglycerides abnormalities. Clinical and laboratory variables were those collected just prior to the lipodystrophy assessment visit (< 3 and < 6 months, respectively).
Data analysis The primary outcomes investigated were fat redistribution (any form) and lipoatrophy. Children characteristics including, age, sex, puberty onset, nutritional status, WHO stage at ART initiation, stavudine, zidovudine and PI treatments and durations, CD4 count, virologic suppression and lipid profiles were compared with the primary outcomes. For each ART drug, recent drug treatment (defined as current treatment or treatment ending within the previous six months), any treatment (defined as drug ever used) and exposure duration were included as separate variables. Associations from univariable analyses were assessed using the Kruskal-Wallis and Wilcoxon rank-sum tests, Chi-square and Fisher's exact, and univariable logistic regression, as appropriate. Risk factors for the primary outcomes were identified using a stepwise multivariable logistic regression.
Explanatory variables with P < 0. 25 in univariable analysis were included in the multivariable models and exited by the stepwise procedure at P ≥ 0. 20. Continuous explanatory variables were categorized before entering the models. Continuous variables are expressed as median with interquartile range (IQR). Odds ratios (OR) and adjusted OR (aOR) are given with their 95% confidence interval (CI) in univariable and multivariable analyses, respectively. Differences were considered statistically significant at P < 0. 05. All statistical analyses were performed in SAS version 9. 3 (SAS Institute, Cary, North Carolina, USA).
Acknowledgments We would like to thank all the participating children and their caregivers. The  ANRS 12279 MAGGSEN Cohort Study Group. Study sites: Centre Hospitalier National d'Enfants Albert Royer, Dakar, Senegal: Haby, Sy Signate ;  Aminata, Diack; Helene, Mbodj; Ndeye Fatou, Diallo; Aissata, Ba; Aicha, Dia; Ndeye Ngone, Have; Astou, Dieye; Oumy, Fall; Rosine, Sonko. Synergie pour l'Enfance/Centre Hospitalier Roi Baudouin, Guediawaye, Senegal: Ngagne, Mbaye; Baly, Ouattara; Abdou, K, Niang; Alhadji, B, Diom; Adama, Ndour; Bigue, Badiane. Study Coordination: Institut de Recherche pour le Développement, Montpellier, France: Cecile, Cames; Lea, Pascal; Philippe, Msellati; Caroline, Desclaux Sall; Suzanne, Izard. Centre de Recherche et de Formation à la Prise en Charge Clinique, Dakar, Senegal: Amady, Ndiaye; Ousseynou, Ndiaye; Binta, Seck.