Biology subjects

Camara, O.

Publications and source records attributed to Camara, O..

8 recordsLinked to original sources

bioRxiv2026

Characterization of Fetal Cortical Development Using Spectral Analysis of Gyrification (SPANGY)

The prenatal period of human brain development is critical for mental health and cognition across the entire lifespan. During this period, the cortex undergoes a dramatic transformation from a smooth lissencephalic surface into an elaborately folded structure, a process whose precise characterization is essential for understanding neurodevelopmental trajectories. This study represents the first application of Spectral Analysis of Gyrification (SPANGY) to a large multi-centric fetal brain MRI dataset (635 subjects, 20-38 weeks gestational age). SPANGY characterizes geometric variations on a surface based on the wavelength of folds, hence, providing a quantitative local description of gyrification at the individual level. Using rigorous normative modeling (GAMLSS) and statistical harmonization (ComBat-GAM), we established age-specific reference trajectories for multi-scale gyrification features (spectral frequency bands). We provide the first ever quantification of the temporally-ordered emergence of cortical folding in successive waves: the earliest-emerging low frequency, deep fissures are progressively superseded by the accelerating expansion of higher frequency folds. The normative curves provide the first step in taking prenatal neurodevelopmental assessment from qualitative inspection into a rigorous statistical inference, creating an objective reference against which deviations from healthy brain growth can be caught earlier, and with greater precision.

neuroscience↗

bioRxiv2026

Data quality biases normative models derived from fetal brain MRI

Normative modeling is increasingly used to characterize typical growth trajectories and identify atypical neurodevelopment, including early brain development using magnetic resonance imaging (MRI) acquired before birth. Recent work has emphasized the importance of large sample sizes for accurate and robust centile estimation. In this study, we investigate how image quality influences fetal brain normative models, a critical factor in this context where MRI is acquired on a moving fetus in utero. Using a multi-centric cohort of 635 fetal MRI scans, we applied a standardized visual quality control (QC) protocol with continuous quality ratings. We fit normative models for multiple brain structures under progressively relaxed QC stringency, and quantified the deviations in centile estimates relative to a high-quality reference subgroup. Our results showed that including lower-quality data systematically biased normative centiles, with the strongest effects observed in the outer centiles, particularly the lower tail (1st-10th). Bias increased progressively as QC stringency was relaxed and could not be attributed solely to the number of subjects used to fit the models. Quality-induced bias was structure-dependent, and often not visually apparent at the segmentation level. These findings highlight that image quality is an important source of bias in normative fetal brain modeling, and that increasing sample size at the expense of quality may systematically affect centile estimates, potentially jeopardizing the utility of the model.

neuroscience↗

bioRxiv2024

The influence of scaffold deformation and fluid mechanical stimuli on bone tissue differentiation.

Bone tissue engineering enables the self-healing of bone fractures avoiding the graft surgery risks. Scaffolds are designed to transfer global mechanical load to cells, and the structure-blood flow interaction is crucial for cell differentiation, proliferation, and migration. Numerical models often consider the effect of solid on the fluid or vice-versa, nevertheless, fluid-structure interactions (FSI) are not usually explored. The present study aims to develop in-silico FSI models to evaluate tissue differentiation capability of different scaffold designs. This is accomplished by analyzing the relation between scaffold strain deformation and fluid mechanical stimuli developed at the cell microscopic level. Cubic regular structures with cylinder and sphere pore based of 60%, 70% and 80% porosity were modelled in finite element analysis. Static or dynamic compression and inlet steady state or transient state fluid profile were considered. Fluid-structure interactions have been performed, and cell differentiation studies considering the octahedral shear strain and fluid shear stress have been compared. Results indicate that high porous scaffold with low compression and fluid perfusion rates promote bone tissue proliferation. Moreover, mechanical stimulation seems to help bone formation and to inhibit cartilage phenotype. Results showed that neglecting the interaction between the scaffold and fluid flow could lead to substantial overestimation of bone differentiation. This study enhances our understanding of the role of dynamic mechanical simulations in tissue formation; allowing the improvement of scaffold design to face complex bone fractures.

bioengineering↗

bioRxiv2024

Inference of alveolar capillary network connectivity from blood flow dynamics

The intricate structure of the lungs is essential for the gas exchange within the alveolar region. Despite extensive research on the pulmonary vasculature, there are still unresolved questions regarding the connection between capillaries and the vascular tree. A major challenge is obtaining comprehensive experimental data that integrates morphological and physiological aspects. We propose a computational approach that combines data-driven 3D morphological modeling with computational fluid dynamics simulations. This method enables investigating the connectivity of the alveolar capillary network with the vascular tree based on the dynamics of blood flow. We developed 3D sheet-flow models to accurately represent the morphology of the alveolar capillary network and conducted computational fluid dynamics simulations to predict flow velocities and pressure distributions. Our approach focuses on leveraging functional features to identify the most plausible architecture of the system. For given capillary flow velocities and arteriole-to-venule pressure drops, we deduce details about arteriole connectivity. Preliminary connectivity analyses for non-human species indicate that their alveolar capillary network of a single alveolus is linked to at least two arterioles with diameters of 20 {micro}m or a single arteriole with a minimum diameter of 30 {micro}m. Our study provides insights into the structure of the pulmonary microvasculature by evaluating blood flow dynamics. This inverse approach represents a new strategy to exploit the intricate relationship between morphology and physiology, applicable to other tissues and organs. In the future, the availability of experimental data will play a pivotal role in validating and refining the hypotheses analyzed with our computational models. New and noteworthyThe alveolus is pivotal for gas exchange. Due to its complex morphology and dynamic nature, structural experimental studies are challenging. Computational modeling offers an alternative. We developed a databased 3D model of the alveolar capillary network and performed blood flow simulations within it. Choosing a novel perspective, we inferred structure from function. We systematically varied properties of vessels connected to our capillary network and compared simulation results with experimental data to obtain plausible vessel configurations.

physiology↗

bioRxiv2024

Impact of occluder device configurations in in-silico left atrial hemodynamics for the analysis of device-related thrombus

Left atrial appendage occlusion devices (LAAO) are a feasible alternative for non-valvular atrial fibrillation (AF) patients at high risk of thromboembolic stroke and contraindication to antithrombotic therapies. However, optimal LAAO device configurations (i.e., size, type, location) remain unstandardized due to the large anatomical variability of the left atrial appendage (LAA) morphology, leading to a 4-6% incidence of device-related thrombus (DRT). In-silico simulations have the potential to assess DRT risk and identify the key factors, such as suboptimal device positioning. This work presents fluid simulation results computed on 20 patient-specific left atrial geometries, analysing different commercially available LAAO occluders, including plug-type and pacifier-type devices. In addition, we explored two distinct device positions: 1) the real post-LAAO intervention configuration derived from follow-up imaging; and 2) one covering the pulmonary ridge if it was not achieved during the implantation (13 out of 20). In total, 33 different configurations were analysed. In-silico indices indicating high risk of DRT (e.g., low blood flow velocities and flow complexity around the device) were combined with particle deposition analysis based on a discrete phase model. The obtained results revealed that covering the pulmonary ridge with the LAAO device may be one of the key factors to prevent DRT. Moreover, disk-based devices exhibited enhanced adaptability to various LAA morphologies and, generally, demonstrated a lower risk of abnormal events after LAAO implantation.

bioengineering↗

bioRxiv2021

Riemannian geometry of functional connectivity matrices for multi-site attention-deficit/hyperactivity disorder data harmonization

The use of multi-site datasets in neuroimaging provides neuroscientists with more statistical power to perform their analyses. However, it has been shown that imaging-site introduces a variability in the data that cannot be attributed to biological sources. In this work, we show that functional connectivity matrices derived from resting-state multi-site data contain a significant imaging-site bias. To this aim, we exploited the fact that functional connectivity matrices belong to the manifold of symmetric positive-definite matrices, making possible to operate on them with Riemannian geometry. We hereby propose a geometry-aware harmonization approach, Rigid Log-Euclidean Translation, that accounts for this site bias. Moreover, we adapted other Riemannian-geometric methods designed for other domain adaptation tasks, and compared them to our proposal. Based on our results, Rigid Log-Euclidean Translation of multi-site functional connectivity matrices seems to be among the studied methods the most suitable one in a clinical setting. This represents an advance with respect to previous functional connectivity data harmonization approaches, which do not respect the geometric constraints imposed by the underlying structure of the manifold. In particular, when applying our proposed method on data from the ADHD-200 dataset, a multi-site dataset built for the study of attention-deficit/hyperactivity disorder, we obtained results that display a remarkable correlation with established pathophysiological findings and, therefore, represent a substantial improvement when compared to the non-harmonization analysis. Thus, we present evidence supporting that harmonization should be extended to other functional neuroimaging datasets, and provide a simple geometric method to address it.

neuroscience↗

bioRxiv2021

Optimal strategy for public good production is set by balancing intertemporal trade-off between population growth rate and carrying capacity

Public goods are biomolecules that contribute to the community welfare. Their production can benefit populations in many ways, such as by providing access to previously unutilized resources. However, public good production has often been energetically costly, resulting in a reduction in the cellular growth rate. To reduce this cost, populations have evolved strategies to regulate biosynthesis of public good. Among these cell densities dependent regulation of public goods, as accomplished by quorum sensing, is a widely studied mechanism. Given that the fitness costs and benefits of public good production must be balanced, adoption of quorum sensing as a regulatory pathway by bacterial cells may have parallels with several economic principles that are used to study optimal investment decisions. Here, we explore the regulation of a public good, whose benefit is an increase in the carrying capacity, through experimental measurements of growth for engineered strains of Escherichia coli and analysis of those results using a modified logistic growth model. By varying the cell density at which the production of the public good was activated, we showed sharply-peaked optimum population fitness. Analysis further revealed that cell density associated with maximum public good benefits was determined by the trade-off between the cost of public good production, in terms of reduced growth rate, and benefits received from public good, in the form of increased carrying capacity. Moreover, our model showed that cells with luxRI quorum sensing seem to upregulate public good expression when the benefits from the production was immediate. These results demonstrate a case where a biological system apparently has evolved to optimize the timing of public good production to account for short-term costs and delays in reaping a future benefit. Author summaryBacteria often cooperate by sharing resources, sometimes referred as public goods. The activity of public good molecules benefits all of the neighboring cells. Here we examine the public good amylase, an enzyme to break down starch into smaller pieces that can be eaten by cells. Amylase production benefits the entire population because it enables growth to a larger population size, but production of this enzyme also has a cost. Enzyme production requires cells to expend energy and cellular resources. To balance the cost and benefit of the production of amylase, cells have likely evolved a strategy to control the timing of the production of public goods. We tested the dependence of population fitness on the timing of amylase production, finding an optimal cell density for amylase production. Finding the balance means that cells have evolved to anticipate future events, such as when simple food sources are depleted. Similar balancing of immediate costs and future benefits has been observed and studied in economics. Our results revealed that cells which use the regulatory strategy quorum sensing to control amylase production have minimized the delay in obtaining a benefit from this public good.

microbiology↗

bioRxiv2018

Ebola outbreak brings to light an unforeseen impact of tsetse control on sleeping sickness transmission in Guinea.

In addition to the thousands of deaths due the unprecedented ebola outbreak that stroke West Africa (2014-2016), national health systems in affected countries were deeply challenged impacting a number of diseases control programs. Here we describe the case of Human African Trypanosomiasis (HAT), a deadly neglected tropical disease due to a trypanosome transmitted by tsetse flies for which no vaccine nor chemoprophylaxis exists. Data are presented for the disease focus of Boffa in Guinea where a pilot elimination project combining medical screening and vector control was launched in 2012. During ebola, HAT active screening activities were postponed and passive surveillance also was progressively impaired. However, tsetse control using small insecticide impregnated targets could be maintained. The over two years disruption of screening activities led to a dramatic increase of HAT prevalence, from 0.7% in 2013 (21/2885) to 2% (69/3448) in 2016, reaching epidemic levels (>5%) in some villages. In deep contrast, control levels reached in 2013 (0.1%; 7/6564) were maintained in areas covered with impregnated targets as no cases were found in 2016 (0/799). In Boffa, ebola has thus incidentally provided a unique framework to assess the impact of current HAT control strategies. A first lesson is that the \"screen and treat\" strategy is fragile as rapid bursts of the disease may occur in case of disruption. A second lesson is that vector control reducing human-tsetse contacts, even implemented alone, is effective in providing a good level of protection against infection. This advocates for a greater attention being paid to the combination of tsetse control together with medical activities in aiming to reach the HAT elimination objective in Africa.

epidemiology↗