Raluca Eftimie

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Verified

Raluca verified their affiliation via an institutional email.

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• PhD
• Professor (Full) at University of Franche-Comté

In this study we review the current state of the art for Dupuytren's disease (DD), while emphasising the need for a better integration of clinical, experimental and quantitative predictive approaches to understand the evolution of the disease and improve current treatments. We start with a brief review of the biology of this disease and current tre...

Brain-related experiments are limited by nature, and so biological insights are often limited or absent. This is particularly problematic in the context of brain cancers, which have very poor survival rates. To generate and test new biological hypotheses, researchers have started using mathematical models that can simulate tumour evolution. However...

The specific structure of the extracellular matrix (ECM), and in particular the density and orientation of collagen fibres, plays an important role in the evolution of solid cancers. While many experimental studies discussed the role of ECM in individual and collective cell migration, there are still unanswered questions about the impact of nonloca...

Transport-dominated partial differential equation models have been used extensively over the past two decades to describe various collective migration phenomena in cell biology and ecology. To understand the behaviour of these models (and the biological systems they describe) different analytical and numerical approaches have been used. While the a...

Background/Objectives: Misdiagnosing skin disorders leads to the administration of wrong treatments, sometimes with life-impacting consequences. Deep learning algorithms are becoming more and more used for diagnosis. While many skin cancer/lesion image classification studies focus on datasets containing dermatoscopic images and do not include keloi...

Transport-dominated partial differential equation models have been used extensively over the past two decades to describe various collective migration phenomena in cell biology and ecology. To understand the behaviour of these models (and the biological systems they describe) different analytical and numerical approaches have been used. While the a...

This study considers a non-local mathematical model for normal and abnormal wound healing described by four equations: an ordinary differential equation for the dynamics of extracellular matrix, and three partial differential equations for the dynamics of growth factors, fibroblasts, and macrophages. Two of these equations include non-local (integr...

Understanding effector and memory immune responses against influenza A virus (IAV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and re-infections is extremely important, given that they are now endemic in the community. The goal of this study is to investigate the role of memory cells and antibodies in the immune resp...

Pattern formation in biological aggregations is a topic of great interest, due to the complex spatial structure of various aggregations of cells/bacteria/animals that can be observed in nature. While many such aggregations look similar at the macroscopic level, they might differ in their microscopic spatial structure. However, the complexity of the...

This paper presents a critical analysis of the literature and perspective research ideas for modeling the epidemics caused by the SARS-CoV-2 virus. It goes beyond deterministic population dynamics to consider several key complexity features of the system under consideration. In particular, the multiscale features of the dynamics from contagion to t...

We consider a one-dimensional nonlocal hyperbolic model introduced to describe the formation and movement of self-organizing collectives of animals in homogeneous 1D environments. Previous research has shown that this model exhibits a large number of complex spatial and spatiotemporal aggregation patterns, as evidenced by numerical simulations and...

Malaria is an infectious and communicable disease, caused by one or more species of Plasmodium parasites. There are five species of parasites responsible for malaria in humans, of which two, Plasmodium Falciparum and Plasmodium Vivax, are the most dangerous. In Djibouti, the two species of Plasmodium are present in different proportions in the infe...

In this study we propose a novel agent-based model to reproduce and propose new hypotheses on the biological mechanisms of cell-cell interactions and cell migration from data obtained during scratch assay with healthy and keloid fibroblasts. The advantage of the agent-based model we propose in this paper lies in its simplicity: only three governing...

Cell segregation caused by collective cell migration (CCM) is crucial for morphogenesis, functional development of tissue parts, and is also an important aspect in other diseases such as cancer and its metastasis process. Efficiency of the cell segregation depends on the interplay between: (1) biochemical processes such as cell signaling and gene e...

Cell segregation caused by collective cell migration (CCM) is crucial for morphogenesis, functional development of tissue parts, and is an important aspect in other diseases such as cancer and its metastasis process. Efficiency of the cell segregation depends on the interplay between: (1) biochemical processes such as cell signaling and gene expres...

Significance Glioblastoma (GBM) is a rare but deadly form of brain tumor with a low median survival rate of 14.6 months, due to its resistance to treatment. An independent simulation of the INtraoperative photoDYnamic therapy for GliOblastoma (INDYGO) trial, a clinical trial aiming to treat the GBM resection cavity with photodynamic therapy (PDT) v...

This paper deals with the modeling and simulation of the in-host dynamics of a virus. The modeling approach was developed according to the idea that mathematical models should go beyond deterministic single-scale population dynamics by taking into account the multiscale, heterogeneous features of the complex system under consideration. Here, we con...

Methicillin-Resistant Staphylococcus Aureus (MRSA) infection can occur alongside or following COVID-19, which is a concern in healthcare settings. The effectiveness of antiviral treatments for COVID-19 depends on a functioning immune response, but antibiotics used for bacterial infections like MRSA can disrupt the immune response and reduce the eff...

Keloids are fibroproliferative disorders described by excessive growth of fibrotic tissue, which also invades adjacent areas (beyond the original wound borders). Since these disorders are specific to humans (no other animal species naturally develop keloid-like tissue), experimental in vivo/in vitro research has not led to significant advances in t...

Epithelial cancer is the one of most lethal cancer type worldwide. Targeting the early stage of disease would allow dramatic improvements in the survival of cancer patients. The early stage of the disease is related to cancer cell spreading across surrounding healthy epithelium. Consequently, deeper insight into cell dynamics along the biointerface...

Cancer invasion through the surrounding epithelium and extracellular matrix (ECM) is the one of the main characteristics of cancer progression. While significant effort has been made to predict cancer cells response under various drug therapies, much less attention has been paid to understand the physical interactions between cancer cells and their...

The movement of cells during (normal and abnormal) wound healing is the result of bio-mechanical interactions that combine cell responses to growth factors as well as cell-cell and cell-matrix interactions (adhesion and remodelling). It is known that cells can communicate and interact locally and non-locally with other cells inside the tissues, thr...

Tissue surface tension is one of the key parameters that govern tissue rearrangement, shaping, and segregation within various compartments during organogenesis, wound healing, and cancer diseases. Deeper insight into the relationship between tissue surface tension and cell residual stress accumulation caused by collective cell migration can help us...

Poster presented at the 2023 STEM for Britain finals at the House of Commons. The research is simulating the treatment of glioblastoma with PDT using MCRT methods.

The keloids are fibroproliferative disorders described by an excessive growth of fibrotic tissue, which also invades adjacent areas (beyond the original wound borders). Since these disorders are specific to humans (no other animal species naturally develop keloid-like tissue), the experimental in vivo/in vitro research has not lead to significant a...

The last few decades have been dominated by the need for digital control of various processes in biology and medicine. Advances in artificial intelligence (AI) over the last few years, and data being generated at extremely high rates and being analyzed and interpreted with the help of AI, have led to new approaches in medicine that include also opt...

The last few decades have been dominated by the need for digital control of various processes in biology and medicine. Advances in artificial intelligence (AI) over the last few years, and data being generated at extremely high rates and being analysed and interpreted with the help of AI, have led to new approaches in medicine that include also opt...

Non Small Cell Lung Cancer (NSCLC) is the most common type of lung cancer, and represents the leading cause of cancer-related deaths worldwide. Experimental studies have shown that these solid cancers are heavily infiltrated with macrophages: anti-tumour M1 macrophages, pro-tumour M2 macrophages, and macrophage subtypes sharing both M1 and M2 prope...

Many SARS-CoV-2 variants have appeared over the last months, and many more will continue to appear. Understanding the competition between these different variants could help make future predictions on the evolution of epidemics. In this study we use a mathematical model to investigate the impact of three different SARS-CoV-2 variants on the spread...

The COVID-19 pandemic has placed a particular burden on hospitals: from intra-hospital transmission of the infections to reduced admissions of non-COVID-19 patients. There are also high costs associated with the treatment of hospitalised COVID-19 patients, as well as reductions in revenues due to delayed and cancelled treatments. In this study we i...

In this study we investigate computationally tumour-oncolytic virus (OV) interactions that take place within a heterogeneous extracellular matrix (ECM). The ECM is viewed as a mixture of two constitutive phases, namely a fibre phase and a non-fibre phase. The multiscale mathematical model presented here focuses on the nonlocal cell-cell and cell-EC...

Rheumatoid arthritis (RA) is a chronic inflammatory disorder that causes pain, swelling and stiffness in the joints, and negatively impacts the life of affected patients. The disease does not have a cure yet, as there are still many aspects of this complex disorder that are not fully understood. While mathematical models can shed light on some of t...

Cancer invasion of the surrounding tissue is a multiscale process of collective cell movement that involves not only tumour cells but also other immune cells in the environment, such as the tumour-associated macrophages (TAMs). The heterogeneity of these immune cells, with the two extremes being the pro-inflammatory and anti-tumour M1 cells, and th...

Cancer cell mutations occur when cells undergo multiple cell divisions, and these mutations can be spontaneous or environmentally-induced. The mechanisms that promote and sustain these mutations are still not fully understood. This study deals with the identification (or reconstruction) of the usually unknown cancer cell mutation law, which lead to...

In this study we investigate computationally tumour-oncolytic virus(OV) interactions that take place within a heterogeneous ExtraCellular Matrix (ECM). The ECM is viewed as a mixture of two constitutive phases, namely a fibre phase and a non-fibre phase. The multiscale mathematical model presented here focuses on the nonlocal cell-cell and cell-ECM...

Cancer cell mutations occur when cells undergo multiple cell divisions, and these mutations can be spontaneous or environmentally-induced. The mechanisms that promote and sustain these mutations are still not fully understood. This study deals with the identification (or reconstruction) of the usually unknown cancer cell mutation law, which lead to...

Brain-related experiments are limited by nature, and so biological insights are often restricted or absent. This is particularly problematic in the context of brain cancers, which have very poor survival rates. To generate and test new biological hypotheses, researchers started using mathematical models that can simulate tumour evolution. However,...

We propose and study computationally a novel non-local multiscale moving boundary mathematical model for tumour and oncolytic virus (OV) interactions when we consider the go or grow hypothesis for cancer dynamics. This spatio-temporal model focuses on two cancer cell phenotypes that can be infected with the OV or remain uninfected, and which can ei...

Collective migration of cells and animals often relies on a specialised set of “leaders”, whose role is to steer a population of naive followers towards some target. We formulate a continuous model to understand the dynamics and structure of such groups, splitting a population into separate follower and leader types with distinct orientation respon...

Macrophages’ role in the evolution of solid tumours is a well accepted fact, with the M1-like macrophages having an anti-tumour role and the M2-like macrophages having a pro-tumour role. Despite the fact that some clinical studies on lung tumours have emphasised also the presence of macrophages with mixed M1 and M2 phenotypes in addition to macroph...

Cancer invasion of the surrounding tissue is a multiscale process that involves not only tumour cells but also other immune cells in the environment, such as the tumour-associated macrophages (TAMs). The heterogeneity of these immune cells, with the two extremes being the pro-inflammatory and anti-tumour M1 cells, and the anti-inflammatory and pro-...

Collective migration of cells and animals often relies on a specialised set of "leaders", whose role is to steer a population of naive followers towards some target. We formulate a continuous model to understand the dynamics and structure of such groups, splitting a population into separate follower and leader types with distinct orientation respon...

The success of oncolytic virotherapies depends on the tumour microenvironment, which contains a large number of infiltrating immune cells. In this theoretical study, we derive an ODE model to investigate the interactions between breast cancer tumour cells, an oncolytic virus (Vesicular Stomatitis Virus), and tumour-infiltrating macrophages with dif...

Healthcare associated transmission of viral infections is a major problem that has significant economic costs and can lead to loss of life. Infections with the highly contagious SARS-CoV-2 virus have been shown to have a high prevalence in hospitals around the world. The spread of this virus might be impacted by the density of patients inside hospi...

Invasion of the surrounding tissue is one of the recognised hallmarks of cancer [32], which is accomplished through a complex heterotypic multiscale dynamics involving tissue-scale random and directed movement of the population of both cancer cells and other accompanying cells (including here, the family of tumour-associated macrophages) as well as...

Oncolytic virus (OV) therapy is a promising treatment for cancer due to the OVs selective ability to infect and replicate inside cancer cells, thus killing them, without harming healthy cells. In this work, we present a new non-local multiscale moving boundary model for the spatio-temporal cancer-OV interactions. This model explores an important do...

Healthcare associated transmission of viral infections is a major problem that has significant economic costs and can lead to loss of life. Infections with the highly contagious SARS-CoV-2 virus have been shown to have a high prevalence in hospitals around the world. The spread of this virus might be impacted by the density of patients inside hospi...

Collective behaviours in animal communities are the result of inter-individual communication. However, communication signals are not fixed; they evolve to ensure more effective interactions between the emitter and receiver of these signals. In this study, we use a mathematical approach and investigate the effect of changes in communication signals...

Progress in shortening the duration of tuberculosis (TB) treatment is hampered by the lack of a predictive model that accurately reflects the diverse environment within the lung. This is important as TB has been shown to produce distinct localisations to different areas of the lung during different disease stages, with the environmental heterogenei...

The heterogeneity and plasticity of macrophages have become a topic of great interest, due to their role in various diseases ranging from cancer to bacterial infections. While initial experimental studies assumed an extreme polarisation situation, with the (anti-tumour) M1 and (pro-tumour) M2 macrophages representing the two extreme cell phenotypes...

Replicating oncolytic viruses provide promising treatment strategies against cancer. However, the success of these viral therapies depends mainly on the complex interactions between the virus particles and the host immune cells. Among these immune cells, macrophages represent one of the first line of defence against viral infections. In this paper,...

Macrophages are one of the most important immune cell populations that can be found inside solid tumours. For a long time, it was thought that these cells have an anti-tumour role, but relatively recent research has shown that they can have both anti-tumour and pro-tumour roles as determined by their phenotypes. Due to the heterogeneity and plastic...

Rheumatoid arthritis is a chronic autoimmune disease that is a major public health challenge. The disease is characterised by inflammation of synovial joints and cartilage erosion, which lead to chronic pain, poor life quality and, in some cases, mortality. Understanding the biological mechanisms behind the progression of the disease, as well as de...

Progress in shortening the duration of tuberculosis (TB) treatment is hampered by the lack of a predictive model that accurately reflects the diverse environment within the lung. This is important as TB has been shown to produce distinct localisations to different areas of the lung during different disease stages, with the environmental heterogenei...

Oncolytic viral therapies is one of the new promising strategies against cancer, due to the ability of oncolytic viruses to specifically replicate inside cancer cells and kill them. There is increasing evidence that a sub-class of viruses that contain fusion proteins (triggering the formation of syncytia) can lead to better oncolytic results. Since...

Rheumatoid arthritis is a chronic autoimmune disease that is a major public health challenge. The disease is characterised by inflammation of synovial joints and cartilage erosion, which leads to chronic pain, poor life quality and, in some cases, premature mortality. Understanding the biological mechanisms behind the progression of the disease, as...

Over the last few years, oncolytic virus therapy has been recognised as a promising approach in cancer treatment, due to the potential of these viruses to induce systemic anti-tumour immunity and selectively killing tumour cells. However, the effectiveness of these viruses depends significantly on their interactions with the host immune responses,...

Two mathematical models described by simple ordinary differential equations are developed to investigate the Hong Kong influenza epidemic during 2017–2018 winter, based on overall epidemic dynamics and different influenza subtypes. The first model, describing the overall epidemic dynamics, provides the starting data for the second model which diffe...

Oncolytic viruses (OV) are viruses that can replicate selectively within cancer cells and destroy them. While the past few decades have seen significant progress related to the use of these viruses in clinical contexts, the success of oncolytic therapies is dampened by the complex spatial tumour-OV interactions. In this work, we present a novel mul...

In this study we start by reviewing a class of 1D hyperbolic/kinetic models (with two velocities) used to investigate the collective behaviour of cells, bacteria or animals. We then focus on a restricted class of nonlocal models that incorporate various inter-individual communication mechanisms, and discuss how the symmetries of these models impact...

The collective movement of animals occurs as a result of communicationbetween the members of the community. However, inter-individual communication can be affected by the stochasticity of the environment, leading to changes in the perception of neighbours and subsequent changes in individual behaviour, which then influence the overall behaviour of...

Tumours consist of heterogeneous populations of cells. The sub-populations can have different features, including cell motility, proliferation and metastatic potential. The interactions between clonal sub-populations are complex, from stable coexistence to dominant behaviours. The cell–cell interactions, i.e. attraction, repulsion and alignment, pr...

Anti-cancer therapies based on oncolytic viruses are emerging as important approaches in cancer treatment. However, the effectiveness of these therapies depends significantly on the interactions between the oncolytic viruses and the host immune response. Macrophages are one of the most important cell types in the anti-viral immune responses, by act...

Background: Early cancer diagnosis is one of the most important challenges of cancer research, since in many cancers it can lead to cure for patients with early stage diseases. For epithelial ovarian cancer (which is the leading cause of death among gynaecologic malignancies) the classical detection approach is based on measurements of CA-125 biom...

Purpose: Explore the heterogeneity in dynamics of tumour response to vemurafenib, dabrafenib and trametinib using routinely collected clinical trial imaging data. Methods: Time-series imaging data from the phase III studies of vemurafenib, dabrafenib and trametinib were collected through a data repository. A mathematical model based on basic mec...

Anti-cancer therapies based on oncolytic viruses are emerging as important approaches in cancer treatment. However, the effectiveness of these therapies depends significantly on the interactions between the oncolytic viruses and the host immune response. Macrophages are one of the most important cell types in the anti-viral immune responses, by act...

While numerical approaches are a very important step in investigating the patterns exhibited by the hyperbolic and kinetic models discussed in the previous chapters, they could be slow and might not offer a full understanding of the models’ dynamics due to the very large parameter space associated with some models. In contrast, stability theory cou...

One-dimensional (1D) models are simple enough to be investigated analytically and numerically. However, they are not very biological realistic since the majority of behaviours observed in nature occur in 2D or 3D. In this chapter we review different types of 2D kinetic models derived to investigate the movement and local/nonlocal interactions of in...

Due to the complexity of hyperbolic and kinetic models discussed in the previous chapters, it is difficult to gain much understanding of the behaviour of the models only from analytical results. As we have already seen throughout this study, numerical approaches are critical when trying to unravel the patterns exhibited by these models. There are a...

The one-equation advection models that are being used to describe the movement of various animal populations have been extensively investigated over the last decades. Since the theory behind these equations is well known (and can be found in any textbook on hyperbolic conservation laws), our goal here is to give the reader a brief review of this th...

The aim of this study was to review some of the local and nonlocal kinetic and hyperbolic models derived over the last few years to investigate movement and pattern formation across different biological communities. The emphasis was on the modelling of various self-organised behaviours for cell/animal aggregations, and the analytical and numerical...

Local hyperbolic systems have been first introduced to describe the movement of a population formed of left-moving and right-moving individuals, in response to the local density of their neighbours. These types of models (also called discrete-speed kinetic models, since they incorporate individual-level information regarding the movement direction...

The first step in the investigation of transport models for aggregation and movement, is represented by the study of one-equation models. To emphasise the complexity of these models, we start with a variety of hyperbolic models for car traffic and pedestrian traffic (since the models for collective movement of pedestrians are a natural extension of...

More and more experimental studies show that nonlocal interactions play a role in the majority of biological aggregations. In this chapter we describe a few classes of hyperbolic models that include nonlocal interactions among cells/bacteria/animals, which can influence (1) their turning behaviour, (2) their speeding behaviour, or (3) both turning...

The directed motion of cell aggregates toward a chemical source occurs in many relevant biological processes. Understanding the mechanisms that control this complex behavior is of great relevance for our understanding of developmental biological processes and many diseases. In this paper, we consider a self-propelled particle model for the movement...

Cells adhere to each other and to the extracellular matrix (ECM) through protein molecules on the surface of the cells. The breaking and forming of adhesive bonds, a process critical in cancer invasion and metastasis, can be influenced by the mutation of cancer cells. In this paper, we develop a nonlocal mathematical model describing cancer cell in...

In this paper, we develop a non-local mathematical model describing cancer cell invasion and movement as a result of integrin-controlled cell–cell adhesion and cell–matrix adhesion, and transforming growth factor-beta (TGF-β) effect on cell proliferation and adhesion, for two cancer cell populations with different levels of mutation. The model cons...

Molecular heterogeneity in tumours leads to variability in drug response both between patients and across lesions within a patient. These sources of variability could be explored through analysis of routinely collected clinical trial imaging data. We applied a mathematical model of tumour growth to analyse both within and between patient variabilit...

It is generally accepted that tumour cells can be eliminated by M1 anti-tumour macrophages and T cells. However, experimental results over the past 10-15 years have shown that B16 mouse melanoma cells can be eliminated by the T cells alone (either Th1 or Th2 sub-types), in the absence of T cells. In some studies, elimination of B16 melanoma was ass...

Despite mounting evidence that oncolytic viruses can be effective in treating cancer, understanding the details of the interactions between tumour cells, oncolytic viruses and immune cells that could lead to tumour control or tumour escape is still an open problem. Mathematical modelling of cancer oncolytic therapies has been used to investigate th...

Despite mounting evidence that oncolytic viruses can be effective in treating cancer, understanding the details of the interactions between tumour cells, oncolytic viruses and immune cells that could lead to tumour control or tumour escape is still an open problem. Mathematical modelling of cancer oncolytic therapies has been used to investigate th...