StochKit-FF: Efficient Systems Biology on Multicore Architectures

The stochastic modelling of biological systems is an informative, and in some cases, very adequate technique, which may however result in being more expensive than other modelling approaches, such as differential equations. We present StochKit-FF, a parallel version of StochKit, a reference toolkit for stochastic simulations. StochKit-FF is based on the FastFlow programming toolkit for multicores and exploits the novel concept of selective memory. We experiment StochKit-FF on a model of HIV infection dynamics, with the aim of extracting information from efficiently run experiments, here in terms of average and variance and, on a longer term, of more structured data.Comment: 14 pages + cover pag

Modeling viral coevolution: HIV multi-clonal persistence and competition dynamics

The coexistence of different viral strains (quasispecies) within the same host are nowadays observed for a growing number of viruses, most notably HIV, Marburg and Ebola, but the conditions for the formation and survival of new strains have not yet been understood. We present a model of HIV quasispecies competition, that describes the conditions of viral quasispecies coexistence under different immune system conditions. Our model incorporates both T and B cells responses, and we show that the role of B cells is important and additive to that of T cells. Simulations of coinfection (simultaneous infection) and superinfection (delayed secondary infection) scenarios in the early stages (days) and in the late stages of the infection (years) are in agreement with emerging molecular biology findings. The immune response induces a competition among similar phenotypes, leading to differentiation (quasi-speciation), escape dynamics and complex oscillations of viral strain abundance. We found that the quasispecies dynamics after superinfection or coinfection has time scales of several months and becomes even slower when the immune system response is weak. Our model represents a general framework to study the speed and distribution of HIV quasispecies during disease progression, vaccination and therapy.Comment: 20 pages, 10 figure

Catheter-Related Late Complications in Cancer Patients During and After the COVID-19 Pandemic: A Retrospective Study

Background: Peripherally Inserted Central Catheters (PICCs) and midline catheters are crucial for chemotherapy and supportive care in cancer patients. Their use requires ongoing monitoring to prevent late complications such as infections, dislodgements, and replacements. The COVID-19 pandemic challenged healthcare systems, potentially increasing these complications due to reduced outpatient services and limited specialized personnel. Objectives: This study compared the incidence of late complications associated with PICCs and midline catheters in cancer patients during and after the COVID-19 pandemic. Methods: A retrospective observational study was conducted at a Cancer Center in Italy from March 2020 to April 2024. Catheter-related complications were divided into two cohorts: during the pandemic (March 2020-March 2022) and post-pandemic (April 2022-April 2024). The primary outcome was the incidence of late complications requiring device removal, categorized as infections, dislodgements, and replacements. Statistical analyses included the Chi-squared test for categorical variables and the Kruskal-Wallis test for continuous variables. Results: Of 4104 PICC and midline catheter placements, 2291 removals were recorded, with 550 (24%) due to late complications-404 during the pandemic and 146 post-pandemic (p < 0.001). Suspected infections were the most frequent complication, significantly higher during the pandemic (p < 0.001). Dislodgements and replacements also decreased markedly post-pandemic. Limited outpatient services and disrupted healthcare workflows likely contributed to higher complication rates during the pandemic. Conclusions: The COVID-19 pandemic negatively impacted catheter management in cancer patients, increasing late complications. The post-pandemic decline highlights the importance of consistent care, infection prevention, remote monitoring, and stronger healthcare resilience to reduce risks in future crises

An integrated modelling approach for R5-X4 mutation and HAART therapy assessment

We have modelled the within-patient evolutionary process during HIV infection using different methodologies. New viral strains arise during the course of HIV infection. These multiple strains of the virus are able to use different coreceptors, in particular the CCR5 and the CXCR4 (R5 and X4 phenotypes, respectively)influence the progression of the disease to the AIDS phase. We present a model of HIV early infection and CTLs response which describes the dynamics of R5 quasispecies, specifying the R5 to X4 switch and effects of immune response. We illustrate dynamics of HIV multiple strains in the presence of multidrug HAART therapy. The HAART combined with X4 strain blocker drugs might help to reduce infectivity and lead to slower progression of disease. On the methodology side, our model represents a paradigm of integrating formal methods and mathematical models as a general framework to study HIV multiple strains during disease progression, and will inch towards providing help in selecting among vaccines and drug therapies. The results presented here are one of the rare cases of methodological cross comparison (stochastic and deterministic) and a novel implementation of model checking in therapy validation

Monocytes Contribute to Differential Immune Pressure on R5 versus X4 HIV through the Adipocytokine Visfatin/NAMPT

Background: The immune system exerts a diversifying selection pressure on HIV through cellular, humoral and innate mechanisms. This pressure drives viral evolution throughout infection. A better understanding of the natural immune pressure on the virus during infection is warranted, given the clinical interest in eliciting and sustaining an immune response to HIV which can help to control the infection. We undertook to evaluate the potential of the novel HIV-induced, monocyte-derived factor visfatin to modulate viral infection, as part of the innate immune pressure on viral populations. Results: We show that visfatin is capable of selectively inhibiting infection by R5 HIV strains in macrophages and resting PBMC in vitro, while at the same time remaining indifferent to or even favouring infection by X4 strains. Furthermore, visfatin exerts a direct effect on the relative fitness of R5 versus X4 infections in a viral competition setup. Direct interaction of visfatin with the CCR5 receptor is proposed as a putative mechanism for this differential effect. Possible in vivo relevance of visfatin induction is illustrated by its association with the dominance of CXCR4-using HIV in the plasma. Conclusions: As an innate factor produced by monocytes, visfatin is capable of inhibiting infections by R5 but not X4 strains, reflecting a potential selective pressure against R5 viruses. © 2012 Van den Bergh et al.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Apparent fractal dimensions in the HMF model

We show that recent observations of fractal dimensions in the space of N body Hamiltonian systems with long range interactions are due to finite N and finite resolution effects. We provide strong numerical evidence that, in the continuum Vlasov limit, a set which initially is not a fractal e.g. a line in 2D remains such for all finite times. We perform this analysis for the Hamiltonian Mean Field HMF model, which describes the motion of a system of N fully coupled rotors. The analysis can be indirectly confirmed by studying the evolution of a large set of initial points for the Chirikov standard ma