Modeling dengue immune responses mediated by antibodies: A qualitative study

Dengue fever is a viral mosquito-borne infection and a major international public health concern. With 2.5 billion people at risk of acquiring the infection around the world, disease severity is influenced by the immunological status of the individual, seronegative or seropositive, prior to natural infection. Caused by four antigenically related but distinct serotypes, DENV-1 to DENV-4, infection by one serotype confers life-long immunity to that serotype and a period of temporary cross-immunity (TCI) to other serotypes. The clinical response on exposure to a second serotype is complex with the so-called antibody-dependent enhancement (ADE) process, a disease augmentation phenomenon when pre-existing antibodies to previous dengue infection do not neutralize but rather enhance the new infection, used to explain the etiology of severe disease. In this paper, we present a minimalistic mathematical model framework developed to describe qualitatively the dengue immunological response mediated by antibodies. Three models are analyzed and compared: (i) primary dengue infection, (ii) secondary dengue infection with the same (homologous) dengue virus and (iii) secondary dengue infection with a different (heterologous) dengue virus. We explore the features of viral replication, antibody production and infection clearance over time. The model is developed based on body cells and free virus interactions resulting in infected cells activating antibody production. Our mathematical results are qualitatively similar to the ones described in the empiric immunology literature, providing insights into the immunopathogenesis of severe disease. Results presented here are of use for future research directions to evaluate the impact of dengue vaccines.A.S, H.F., and E.S. E.S. has received funded from the Indonesian RistekBrin Grant No. 122M/IT1.C02/TA.00/2021, 2021 (previously RistekDikti 2018-2021). M.A. received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No 792494

Modeling Dengue Immune Responses Mediated by Antibodies: Insights on the Biological Parameters to Describe Dengue Infections

Dengue fever is a viral mosquito-borne disease, a significant global health concern, with more than one third of the world population at risk of acquiring the disease. Caused by 4 antigenically distinct but related virus serotypes, named DENV-1, DENV-2, DENV-3, and DENV-4, infection by one serotype confers lifelong immunity to that serotype and a short period of temporary cross immunity to other related serotypes. Severe dengue is epidemiologically associated with a secondary infection caused by a heterologous serotype via the so-called antibody-dependent enhancement (ADE), an immunological process enhancing a new infection. Within-host dengue modeling is restricted to a small number of studies so far. With many open questions, the understanding of immunopathogenesis of severe disease during recurrent infections is important to evaluate the impact of newly licensed vaccines. In this paper, we revisit the modeling framework proposed by Sebayang et al. and perform a detailed sensitivity analysis of the well-known biological parameters and its possible combinations to understand the existing data sets. Using numerical simulations, we investigate features of viral replication, antibody production, and infection clearance over time for three possible scenarios: primary infection, secondary infection caused by homologous serotype, and secondary infection caused by heterologous serotype. Besides, describing well the infection dynamics as reported in the immunology literature, our results provide information on parameter combinations to best describe the differences on the immunological dynamics of secondary infections with homologous and heterologous viruses. The results presented here will be used as baseline to investigate a more complex within-host dengue model.Marie Skłodowska-Curie grant agreement No 79249

Birkhoff type decompositions and the Baker-Campbell-Hausdorff recursion

We describe a unification of several apparently unrelated factorizations arisen from quantum field theory, vertex operator algebras, combinatorics and numerical methods in differential equations. The unification is given by a Birkhoff type decomposition that was obtained from the Baker-Campbell-Hausdorff formula in our study of the Hopf algebra approach of Connes and Kreimer to renormalization in perturbative quantum field theory. There we showed that the Birkhoff decomposition of Connes and Kreimer can be obtained from a certain Baker-Campbell-Hausdorff recursion formula in the presence of a Rota-Baxter operator. We will explain how the same decomposition generalizes the factorization of formal exponentials and uniformization for Lie algebras that arose in vertex operator algebra and conformal field theory, and the even-odd decomposition of combinatorial Hopf algebra characters as well as to the Lie algebra polar decomposition as used in the context of the approximation of matrix exponentials in ordinary differential equations.Comment: accepted for publication in Comm. in Math. Phy

Estimating the inelasticity with the information theory approach

Using the information theory approach, in both its extensive and nonextensive versions, we estimate the inelasticity parameter $K$ of hadronic reactions together with its distribution and energy dependence from $p\bar{p}$ and $pp$ data. We find that the inelasticity remains essentially constant in energy except for a variation around $K\sim 0.5$, as was originally expected.Comment: 14 pages, 8 figures. Misprints correcte

PREDICT-GTN 1: Can we improve the FIGO scoring system in gestational trophoblastic neoplasia?

Gestational trophoblastic neoplasia (GTN) patients are treated according to the eight-variable International Federation of Gynaecology and Obstetrics (FIGO) scoring system, that aims to predict first-line single-agent chemotherapy resistance. FIGO is imperfect with one-third of low-risk patients developing disease resistance to first-line single-agent chemotherapy. We aimed to generate simplified models that improve upon FIGO. Logistic regression (LR) and multilayer perceptron (MLP) modelling (n = 4191) generated six models (M1-6). M1, all eight FIGO variables (scored data); M2, all eight FIGO variables (scored and raw data); M3, nonimaging variables (scored data); M4, nonimaging variables (scored and raw data); M5, imaging variables (scored data); and M6, pretreatment hCG (raw data) + imaging variables (scored data). Performance was compared to FIGO using true and false positive rates, positive and negative predictive values, diagnostic odds ratio, receiver operating characteristic (ROC) curves, Bland-Altman calibration plots, decision curve analysis and contingency tables. M1-6 were calibrated and outperformed FIGO on true positive rate and positive predictive value. Using LR and MLP, M1, M2 and M4 generated small improvements to the ROC curve and decision curve analysis. M3, M5 and M6 matched FIGO or performed less well. Compared to FIGO, most (excluding LR M4 and MLP M5) had significant discordance in patient classification (McNemar's test P < .05); 55-112 undertreated, 46-206 overtreated. Statistical modelling yielded only small gains over FIGO performance, arising through recategorisation of treatment-resistant patients, with a significant proportion of under/overtreatment as the available data have been used a priori to allocate primary chemotherapy. Streamlining FIGO should now be the focus

Measurements of long-range near-side angular correlations in sNN=5\sqrt{s_{\text{NN}}}=5TeV proton-lead collisions in the forward region

Two-particle angular correlations are studied in proton-lead collisions at a nucleon-nucleon centre-of-mass energy of $\sqrt{s_{\text{NN}}}=5$TeV, collected with the LHCb detector at the LHC. The analysis is based on data recorded in two beam configurations, in which either the direction of the proton or that of the lead ion is analysed. The correlations are measured in the laboratory system as a function of relative pseudorapidity, $\Delta\eta$, and relative azimuthal angle, $\Delta\phi$, for events in different classes of event activity and for different bins of particle transverse momentum. In high-activity events a long-range correlation on the near side, $\Delta\phi \approx 0$, is observed in the pseudorapidity range $2.0<\eta<4.9$. This measurement of long-range correlations on the near side in proton-lead collisions extends previous observations into the forward region up to $\eta=4.9$. The correlation increases with growing event activity and is found to be more pronounced in the direction of the lead beam. However, the correlation in the direction of the lead and proton beams are found to be compatible when comparing events with similar absolute activity in the direction analysed.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2015-040.htm

Evidence for the strangeness-changing weak decay Ξb−→Λb0π−\Xi_b^-\to\Lambda_b^0\pi^-

Using a $pp$ collision data sample corresponding to an integrated luminosity of 3.0~fb$^{-1}$, collected by the LHCb detector, we present the first search for the strangeness-changing weak decay $\Xi_b^-\to\Lambda_b^0\pi^-$. No $b$ hadron decay of this type has been seen before. A signal for this decay, corresponding to a significance of 3.2 standard deviations, is reported. The relative rate is measured to be ${{f_{\Xi_b^-}}\over{f_{\Lambda_b^0}}}{\cal{B}}(\Xi_b^-\to\Lambda_b^0\pi^-) = (5.7\pm1.8^{+0.8}_{-0.9})\times10^{-4}$, where $f_{\Xi_b^-}$ and $f_{\Lambda_b^0}$ are the $b\to\Xi_b^-$ and $b\to\Lambda_b^0$ fragmentation fractions, and ${\cal{B}}(\Xi_b^-\to\Lambda_b^0\pi^-)$ is the branching fraction. Assuming $f_{\Xi_b^-}/f_{\Lambda_b^0}$ is bounded between 0.1 and 0.3, the branching fraction ${\cal{B}}(\Xi_b^-\to\Lambda_b^0\pi^-)$ would lie in the range from $(0.57\pm0.21)\%$ to $(0.19\pm0.07)\%$.Comment: 7 pages, 2 figures, All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2015-047.htm