Primary pleural leiomyosarcoma with rapid progression and fatal outcome: a case report

Introduction

Leiomyosarcomas are neoplasms of smooth muscles that most commonly arise from the uterus, gastrointestinal tract, or soft tissue. Primary pleural leiomyosarcoma is extremely rare. To the best of our knowledge, only nine cases have been published to date. Because of the rarity of pleural leiomyosarcoma and its similarity (clinical and histological) to other pleural neoplasms, particularly sarcomatous mesothelioma, diagnosis is often difficult.

Case presentation

A 58-year-old North African man was admitted with complaints of dyspnea and chest pain to our hospital. Chest computed tomography revealed right pleural effusion and pleural thickening. A transthoracic needle biopsy yielded a diagnosis of leiomyosarcoma, and tumor cells were strongly and uniformly positive for vimentin, a smooth muscle actin at immunohistochemical analysis. A general examination did not show any metastatic lesions in other areas. One month after diagnosis, the tumor grew rapidly, with pulmonary invasion, and therefore he was treated only by palliative care. He died from respiratory failure one month later. Because no organ of origin of the leiomyosarcoma, other than the pleura, was detected, this case was diagnosed as a primary pleural leiomyosarcoma.

Conclusions

Although leiomyosarcoma originating from the pleura is rare, this entity is increasingly described. The purpose of presenting this case report is to raise awareness among clinicians to consider this clinical entity as a differential diagnosis when a pleural mass is identified.     

Spatiotemporal receptive fields: a dynamical model derived from cortical architectonics

We assume that the mammalian neocortex is built up out of some six layers which differ in their morphology and their external connections. Intrinsic connectivity is largely excitatory, leading to a considerable amount of positive feedback. The majority of cortical neurons can be divided into two main classes: the pyramidal cells, which are said to be excitatory, and local cells (most notably the non-spiny stellate cells), which are said to be inhibitory. The form of the dendritic and axonal arborizations of both groups is discussed in detail. This results in a simplified model of the cortex as a stack of six layers with mutual connections determined by the principles of fibre anatomy. This stack can be treated as a multi-input-multi-output system by means of the linear systems theory of homogeneous layers. The detailed equations for the simulation are derived in the Appendix. The results of the simulations show that the temporal and spatial behaviour of an excitation distribution cannot be treated separately. Further, they indicate specific processing in the different layers and some independence from details of wiring. Finally, the simulation results are applied to the theory of visual receptive fields. This yields some insight into the mechanisms possibly underlying hypercomplexity, putative nonlinearities, lateral inhibition, oscillating cell responses, and velocity-dependent tuning curves.     

Smoking epidemic eradication in a eco-epidemiological dynamical model

Smoking is perceived as a major epidemic with regard to mortality. Modelling is a major tool used to obtain insight in the dynamics and possible solutions to decrease or even eradicate this epidemic. Most models on smoking consider the epidemiological context explicitly, in which smoking is regarded as an ‘infectious disease’, in which individuals ‘infect’ each other. However, the population dynamics are often ignored, while these occur at roughly the same timescale as smoking, and hence should explicitly be considered in the modelling of smoking. We present a simple but dynamical eco-epidemiological model. The model formulation consists of a resource-population dynamic part coupled to an epidemiological part resembling a SIR type model for the three compartments: non-smokers, smokers and ex-smokers. The coupling is via birth of non-smokers and death of the three classes with different death rates. The final four-dimensional system of ordinary differential equations are studied using brute force simulations for the short term dynamics and bifurcation analysis for the long-term dynamics. Due to a feed-back mechanism of the two coupling terms there is a codim-two tangent-transcritical bifurcation. This leads to bi-stability of one smoker endemic interior equilibrium and a smoker free boundary equilibrium. Changing parameters beyond the emerging tangent bifurcation leads on the short term to eradicating smoking. We consider the Netherlands in this paper for parametrization, but the modelling approach may be generally applicable.     

A dynamical model for a co-operative enzyme.

Proteins partially immersed in the hydrophobic portion of a lipid bilayer interact by means of London-van der Waals non-bonding dispersion forces. Moreover, in certain organelles, enzymes are structured in a lattice or ordered matrix. These conditions may facilitate the establishment of long-range correlations between proteins. We studied the dynamical properties of a model for an enzyme endowed with a highly co-operative conformational transition between two reactive states. Two cases were considered, a closed system and an open system. In the closed system for different degrees of interaction among the proteins, it was found that for a substrate concentration greater than a certain threshold an abrupt change of enzymatic activity occurs. This biphasic behavior has been observed in the enzymatic activity of crystalline mitochondrial aspartate aminotransferase and for some other crystalline enzymes. In the analysis of the open system, for a specific input rate of the substrate, two different dynamics were found depending on the selected degree of interaction. For a certain value of a parameter phi, representing the degree of interaction among the reacting units, three steady states co-exist. This multiplicity confers excitable properties to the model. For larger values of phi, limit cycle type solutions were obtained. Thus, a sustained oscillatory product formation of the enzymatic reaction is observed. These results are compared with experimental observations of enzyme extracts detected by NMR.     

A dynamical model of communities and a new species-abundance distribution

It is known to many field biologists that biosurveys of natural communities tend to produce a J-shaped curve when the numbers of species are plotted against abundance. In other words, when the number of species of abundance k is plotted against k (running from 1 to some large number), the resulting distribution peaks at the lowest abundance, then forms a concave ramp as it approaches zero at the far end of the abundance axis. Does this distribution represent a single formula operating behind the scenes, or does it represent several formulas, appropriate for different types of community? Or does it represent no particular formula at all? The research reported here has three components: (1) The analysis of a new dynamical system that simulates multispecies communities (producing J-curves in the process) and the derivation of the "logistic-J" distribution, as the underlying community equilibrium curve; (2) the summary of a general theory of sampling as a bridge between natural communities and samples of them; (3) the evaluation of extant proposals for species-abundance distributions by application of a general theory of sampling or by cross-comparison via 100 biosurveys randomly selected from the literature.     

Cadherin-dependent cell morphology in an epithelium: constructing a quantitative dynamical model

Cells in the Drosophila retina have well-defined morphologies that are attained during tissue morphogenesis. We present a computer simulation of the epithelial tissue in which the global interfacial energy between cells is minimized. Experimental data for both normal cells and mutant cells either lacking or misexpressing the adhesion protein N-cadherin can be explained by a simple model incorporating salient features of morphogenesis that include the timing of N-cadherin expression in cells and its temporal relationship to the remodeling of cell-cell contacts. The simulations reproduce the geometries of wild-type and mutant cells, distinguish features of cadherin dynamics, and emphasize the importance of adhesion protein biogenesis and its timing with respect to cell remodeling. The simulations also indicate that N-cadherin protein is recycled from inactive interfaces to active interfaces, thereby modulating adhesion strengths between cells.     

Rouleau formation of erythrocytes: A dynamical model

A model is presented for the nonBrownian motion of living erythrocytes suspended in their own plasma as observed by Rowlands et al. On the basis of this model, the formation of rouleaux (contractile fibrils among interacting erythrocytes) can be described in terms of an organization of the molecules (mainly fibrinogen) present in blood plasma; this organization is sustained by the nonlinear propagation of electric vibrations generated by red blood cells (coherent electric vibrations of the Fröhlich type).A number of peculiar experimental features otherwise unexplained can also be taken into account in the framework of the model.     

The dynamical Matryoshka model: 3. Diffusive nature of the atomic motions contained in a new dynamical model for deciphering local lipid dynamics

In accompanying papers [Bicout et al., BioRxiv https://doi.org/10.1101/2021.09.21.461198 (2021); Cissé et al., BioRxiv https://doi.org/10.1101/2022.03.30.486370 (2022)], a new model called Matryoshka model has been proposed to describe the geometry of atomic motions in phospholipid molecules in bilayers and multilamellar vesicles based on their quasielastic neutron scattering (QENS) spectra. Here, in order to characterize the relaxational aspects of this model, the energy widths of the QENS spectra of the samples were analyzed first in a model-free way. The spectra were decomposed into three Lorentzian functions, which are classified as slow, intermediate, and fast motions depending on their widths. The analysis provides the diffusion coefficients, residence times, and geometrical parameters for the three classes of motions. The results corroborate the parameter values such as the amplitudes and the mobile fractions of atomic motions obtained by the application of the Matryoshka model to the same samples. Since the current analysis was carried out independently of the development of the Matryoshka model, the present results enhance the validity of the model. The model will serve as a powerful tool to decipher the dynamics of lipid molecules not only in model systems, but also in more complex systems such as mixtures of different kinds of lipids or natural cell membranes.     

Estimating a predator-prey dynamical model with the parameter cascades method

Summary .   Ordinary differential equations (ODEs) are widely used in ecology to describe the dynamical behavior of systems of interacting populations. However, systems of ODEs rarely provide quantitative solutions that are close to real field observations or experimental data because natural systems are subject to environmental and demographic noise and ecologists are often uncertain about the correct parameterization. In this article we introduce "parameter cascades" as an improved method to estimate ODE parameters such that the corresponding ODE solutions fit the real data well. This method is based on the modified penalized smoothing with the penalty defined by ODEs and a generalization of profiled estimation, which leads to fast estimation and good precision for ODE parameters from noisy data. This method is applied to a set of ODEs originally developed to describe an experimental predator–prey system that undergoes oscillatory dynamics. The new parameterization considerably improves the fit of the ODE model to the experimental data sets. At the same time, our method reveals that important structural assumptions that underlie the original ODE model are essentially correct. The mathematical formulations of the two nonlinear interaction terms (functional responses) that link the ODEs in the predator–prey model are validated by estimating the functional responses nonparametrically from the real data. We suggest two major applications of "parameter cascades" to ecological modeling: It can be used to estimate parameters when original data are noisy, missing, or when no reliable priori estimates are available; it can help to validate the structural soundness of the mathematical modeling approach.     

Candida Sepsis: a New Entity?

Despite progress in the field of biological sciences, a definitive diagnosis of Candida sepsis remains an elusive target. Candida, which is frequently found in non-immunocompromised patients in intensive care units, causes severe sepsis, septic shock, and multiple-organ failure in a similar fashion as bacteria. Despite its imprecision, the blood and/or sterile-site culture is still the gold standard for diagnosis, although new biological markers are becoming available for earlier and more accurate diagnosis of invasive candidiasis. Mortality remains high due to a number of factors, and early initiation of appropriate antifungal therapy is a critical factor in positive outcomes. Echinocandins are the drug of choice for severe Candida infections in hospitalized patients. Antifungal stewardship programs may decrease the likelihood of resistance strains, and preventive measures are becoming available to lower the rate of fungal infections in intensive care units.     

On the dynamical properties of a model of cell differentiation

One of the major challenges in complex systems biology is that of providing a general theoretical framework to describe the phenomena involved in cell differentiation, i.e., the process whereby stem cells, which can develop into different types, become progressively more specialized. The aim of this study is to briefly review a dynamical model of cell differentiation which is able to cover a broad spectrum of experimentally observed phenomena and to present some novel results.     

A dynamical model for phospholipid-calcium binding

A model for an isothermal gel-liquid crystalline transition induced by ionic binding is proposed. A Ginsburg-Landau functional was used to describe the long-range order that spontaneously arises during the transition. By calculation of the corresponding chemical potential we obtain the mass current of phospholipids in gel-phase described by an order parameter. In the conservation of mass equation the kinetics of the phospholipids-calcium interaction is introduced, together with the flux divergency. A circular membrane is considered for the analysis, so that the model can be studied in polar coordinates. A solution approximated to first order shows an heterogeneous distribution of domains of phospholipids in gel and liquid crystalline phases. These spatial domains have been detected experimentally by diverse methods in vesicles and cellular membranes. Spatial heterogeneities may cause destabilization of the membrane in the boundaries between domains. This may explain the enhanced vesicle fusion observed in the presence of Ca2+.     

Delayed information induces oscillations in a dynamical model for infectious disease

During disease outbreak,it has been observed that information about the disease prevalence induces the individuafs behavioral changes.This information is usually assumed to be generated by the density of infective individuals and active mass media.The delay in reporting of these infective individuals may have its impact on generated information.Hence,to study the impact of delay on information generation,and therefore on the disease dynamics,a delay differential equation model is proposed and analyzed.The dynamics of information with delay effect is also modeled by a separate rate equation.Model analysis is performed and a unique infected equilibrium is obtained when the basic reproduction number(R0)is greater than one,whereas the disease free equilibrium always exists.When R0<1,the disease free equilibrium is found to be locally stable independent of delay effect.The unique infected equilibrium is found to be locally stable till delay reaches a threshold value.The global stability of the unique infected equilibrium is also established under some parametric conditions by constructing a suitable Lyapunov function.The occurrence of Hopf bifurcation is observed when the delay in information crosses the threshold value.Analytically,the direction and stability of bifurcating periodic solutions is established.Further,we observed the occurrence of Hopf-Hopf bifurcation at two different delays.At first delay threshold,the endemic equilibrium loses its st ability and produces periodic oscillations via Hopf bifurcation.It further regains its stability at second delay threshold via another Hopf bifurcation.Hence,the delay effect on information shows possibility of stability switches.Numerical experiments are carried out to support the obtained analytical results.Our study infers that the disease will show persistent oscillations if there is a significant time lag in reporting of infective after the disease outbreak.Thus,the delay in dissemination of information shows rich and complex dynamics in the model and provides important insights.We also observe numerically that the saturation in information plays a significant role on stability of infected equilibrium in presence of delay.     

Bayesian denoising framework of phonocardiogram based on a new dynamical model

In this paper, we introduce a model-based Bayesian denoising framework for phonocardiogram (PCG) signals. The denoising framework is founded on a new dynamical model for PCG, which is capable of generating realistic synthetic PCG signals. The introduced dynamical model is based on PCG morphology and is inspired by electrocardiogram (ECG) dynamical model proposed by McSharry et al. and can represent various morphologies of normal PCG signals. The extended Kalman smoother (EKS) is the Bayesian filter that is used in this study. In order to facilitate the adaptation of the denoising framework to each input PCG signal, the parameters are selected automatically from the input signal itself. This approach is evaluated on several PCGs recorded on healthy subjects, while artificial white Gaussian noise is added to each signal, and the SNR and morphology of the outputs of the proposed denoising approach are compared with the outputs of the wavelet denoising (WD) method. The results of the EKS demonstrate better performance than WD over a wide range of PCG SNRs. The new PCG dynamical model can also be employed to develop other model-based processing frameworks such as heart sound segmentation and compression.     

The dynamical implications of human behaviour on a social-ecological harvesting model

The dynamic aspects of human harvesting behaviour are often overlooked in resource management, such that models often neglect the complexities of dynamic human effort. Some researchers have recognized this, and a recent push has been made to understand how human behaviour and ecological systems interact through dynamic social-ecological systems. Here, we use a recent example of a social-ecological dynamical systems model to investigate the relationship between harvesting behaviour and the dynamics and stability of a harvested resource, and search for general rules in how relatively simple human behaviours can either stabilize or destabilize resource dynamics and yield. Our results suggest that weak to moderate behavioural and effort responses tend to stabilize dynamics by decreasing return times to equilibria or reducing the magnitude of cycles; however, relatively strong human impacts can readily lead to human-driven cycles, chaos, long transients and alternate states. Importantly, we further show that human-driven cycles are characteristically different from typical resource-driven cycles and, therefore, may be differentiated in real ecosystems. Given the potentially dramatic implications of harvesting on resource dynamics, it becomes critical to better understand how human behaviour determines harvesting effort through dynamic social-ecological systems.     

Self-thinning and community persistence in a simple size-structured dynamical model of plant growth

This paper presents a size-structured dynamical model of plant growth. The model takes the form of a partial differential-integral equation and includes the effects of self- shading by leaves. Closed form solutions are presented for the equilibrium size density distribution. Analytic conditions are derived for community persistence, and the self-thinning exponent is obtained as a function of species characteristics and environmental conditions.     

Sepsis leads to thyroid impairment and dysfunction in rat model

Sepsis was a systemic response to a local infection. Apoptosis was observed in the experimental sepsis. In this study, cecal ligation and puncture (CLP)-induced sepsis was established in rats. We found that sepsis decreased thyroid hormone levels, including triiodothyronine (T3), thyroxine (T4), free T3 (fT3), and free T4 (fT4). Besides, we detected the increasing expression level of Caspase-3 and increasing ratio of TUNEL positive cells in the thyroid after sepsis. Furthermore, a series of pathological ultrastructural changes were observed in thyroid follicular epithelial cells by CLP-induced sepsis. This study established a sepsis animal model and provided the cellular and molecular basis for decoding the pathological mechanism in thyroid with the occurrence of sepsis.