An electric field modeling study with meta-analysis to understand the antidepressant effects of transcranial direct current stimulation (tDCS)

Objective: Transcranial direct current stimulation (tDCS) has mixed effects for major depressive disorder (MDD) symptoms, partially owing to large inter-experimental variability in tDCS protocols and their correlated induced electric fields (E-fields). We investigated whether the E-field strength of distinct tDCS parameters was associated with antidepressant effect. Methods: A meta-analysis was performed with placebo-controlled clinical trials of tDCS enrolling MDD patients. PubMed, EMBASE, and Web of Science were searched from inception to March 10, 2023. Effect sizes of tDCS protocols were correlated with E-field simulations (SimNIBS) of brain regions of interest (bilateral dorsolateral prefrontal cortex [DLPFC] and bilateral subgenual anterior cingulate cortex [sgACC]). Moderators of tDCS responses were also investigated. Results: A total of 20 studies were included (21 datasets, 1,008 patients), using 11 distinct tDCS protocols. Results revealed a moderate effect for MDD (g = 0.41, 95%CI 0.18-0.64), while cathode position and treatment strategy were found to be moderators of response. A negative association between effect size and tDCS-induced E-field magnitude was seen, with stronger E-fields in the right frontal and medial parts of the DLPFC (targeted by the cathode) leading to smaller effects. No association was found for the left DLPFC and the bilateral sgACC. An optimized tDCS protocol is proposed. Conclusions: Our results highlight the need for a standardized tDCS protocol in MDD clinical trials. Registration number: PROSPERO CRD42022296246.

Current progress of computational modeling for guiding clinical atrial fibrillation ablation / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Atrial fibrillation (AF) is one of the most common arrhythmias, associated with high morbidity, mortality, and healthcare costs, and it places a significant burden on both individuals and society. Anti-arrhythmic drugs are the most commonly used strategy for treating AF. However, drug therapy faces challenges because of its limited efficacy and potential side effects. Catheter ablation is widely used as an alternative treatment for AF. Nevertheless, because the mechanism of AF is not fully understood, the recurrence rate after ablation remains high. In addition, the outcomes of ablation can vary significantly between medical institutions and patients, especially for persistent AF. Therefore, the issue of which ablation strategy is optimal is still far from settled. Computational modeling has the advantages of repeatable operation, low cost, freedom from risk, and complete control, and is a useful tool for not only predicting the results of different ablation strategies on the same model but also finding optimal personalized ablation targets for clinical reference and even guidance. This review summarizes three-dimensional computational modeling simulations of catheter ablation for AF, from the early-stage attempts such as Maze III or circumferential pulmonary vein isolation to the latest advances based on personalized substrate-guided ablation. Finally, we summarize current developments and challenges and provide our perspectives and suggestions for future directions.

Biological pacemaker: from biological experiments to computational simulation / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Pacemaking dysfunction has become a significant disease that may contribute to heart rhythm disorders, syncope, and even death. Up to now, the best way to treat it is to implant electronic pacemakers. However, these have many disadvantages such as limited battery life, infection, and fixed pacing rate. There is an urgent need for a biological pacemaker (bio-pacemaker). This is expected to replace electronic devices because of its low risk of complications and the ability to respond to emotion. Here we survey the contemporary development of the bio-pacemaker by both experimental and computational approaches. The former mainly includes gene therapy and cell therapy, whilst the latter involves the use of multi-scale computer models of the heart, ranging from the single cell to the tissue slice. Up to now, a bio-pacemaker has been successfully applied in big mammals, but it still has a long way from clinical uses for the treatment of human heart diseases. It is hoped that the use of the computational model of a bio-pacemaker may accelerate this process. Finally, we propose potential research directions for generating a bio-pacemaker based on cardiac computational modeling.

Biological pacemaker: from biological experiments to computational simulation / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Pacemaking dysfunction has become a significant disease that may contribute to heart rhythm disorders, syncope, and even death. Up to now, the best way to treat it is to implant electronic pacemakers. However, these have many disadvantages such as limited battery life, infection, and fixed pacing rate. There is an urgent need for a biological pacemaker (bio-pacemaker). This is expected to replace electronic devices because of its low risk of complications and the ability to respond to emotion. Here we survey the contemporary development of the bio-pacemaker by both experimental and computational approaches. The former mainly includes gene therapy and cell therapy, whilst the latter involves the use of multi-scale computer models of the heart, ranging from the single cell to the tissue slice. Up to now, a bio-pacemaker has been successfully applied in big mammals, but it still has a long way from clinical uses for the treatment of human heart diseases. It is hoped that the use of the computational model of a bio-pacemaker may accelerate this process. Finally, we propose potential research directions for generating a bio-pacemaker based on cardiac computational modeling.

Diagnostic Accuracy of a Novel On-site Virtual Fractional Flow Reserve Parallel Computing System

Spatial reproducibility of complex fractionated atrial electrogram depending on the direction and configuration of bipolar electrodes: an in-silico modeling study

Although 3D-complex fractionated atrial electrogram (CFAE) mapping is useful in radiofrequency catheter ablation for persistent atrial fibrillation (AF), the directions and configuration of the bipolar electrodes may affect the electrogram. This study aimed to compare the spatial reproducibility of CFAE by changing the catheter orientations and electrode distance in an in-silico left atrium (LA). We conducted this study by importing the heart CT image of a patient with AF into a 3D-homogeneous human LA model. Electrogram morphology, CFAE-cycle lengths (CLs) were compared for 16 different orientations of a virtual bipolar conventional catheter (conv-cath: size 3.5 mm, inter-electrode distance 4.75 mm). Additionally, the spatial correlations of CFAE-CLs and the percentage of consistent sites with CFAE-CL<120 ms were analyzed. The results from the conv-cath were compared with that obtained using a mini catheter (mini-cath: size 1 mm, inter-electrode distance 2.5 mm). Depending on the catheter orientation, the electrogram morphology and CFAE-CLs varied (conv-cath: 11.5±0.7% variation, mini-cath: 7.1±1.2% variation), however the mini-cath produced less variation of CFAE-CL than conv-cath (p<0.001). There were moderate spatial correlations among CFAE-CL measured at 16 orientations (conv-cath: r=0.3055±0.2194 vs. mini-cath: 0.6074±0.0733, p<0.001). Additionally, the ratio of consistent CFAE sites was higher for mini catheter than conventional one (38.3±4.6% vs. 22.3±1.4%, p<0.05). Electrograms and CFAE distribution are affected by catheter orientation and electrode configuration in the in-silico LA model. However, there was moderate spatial consistency of CFAE areas, and narrowly spaced bipolar catheters were less influenced by catheter direction than conventional catheters.

Computer graphics applied to anatomy: a study of two Bio-CAD modeling methods on finite element analysis of human edentulous hemi-mandible / Computación gráfica aplicada a la anatomía: un estudio de dos métodos de modelización Bio-CAD sobre el análisis de elementos finitos de hemimandíbulas edéntulas humanas

Modeling is a step to perform a finite element analysis. Different methods of model construction are reported in literature, as the Bio-CAD modeling. The purpose of this study was to perform a model evaluation and application using two methods of Bio-CAD modeling from human edentulous hemi-mandible on the finite element analysis. From CT scans of dried human skull was reconstructed a stereolithographic model. Two methods of modeling were performed: STL conversion approach (Model 1) associated to STL simplification and reverse engineering approach (Model 2). For finite element analysis was used the action of lateral pterygoid muscle as loading condition to assess total displacement (D), equivalent von-Mises stress (VM) and maximum principal stress (MP). Two models presented differences on the geometry regarding surface number (1834 (model 1); 282 (model 2)). Were observed differences in finite element mesh regarding element number (30428 nodes/16683 elements (model 1); 15801 nodes/8410 elements (model 2). D, VM and MP stress areas presented similar distribution in two models. The values were different regarding maximum and minimum values of D (ranging 0­0.511 mm (model 1) and 0­0.544 mm (model 2), VM stress (6.36E-04­11.4 MPa (model 1) and 2.15E-04­14.7 MPa (model 2) and MP stress (-1.43­9.14 MPa (model 1) and -1.2­11.6 MPa (model 2). From two methods of Bio-CAD modeling, the reverse engineering presented better anatomical representation compared to the STL conversion approach. The models presented differences in the finite element mesh, total displacement and stress distribution.

El modelado es un paso para llevar a cabo un análisis de elementos finitos. Entre los diferentes métodos de construcción del modelo que se presentan en la literatura, está el modelado Bio-CAD. El propósito de este estudio fue realizar una evaluación del modelo y aplicación utilizando dos métodos de modelado de Bio-CAD desde la hemimandíbula humana edéntula en el análisis de elementos finitos. Desde tomografías computarizadas de cráneos humanos secos, fue reconstruido un modelo de estereolitografía. Se realizaron dos métodos de modelización: enfoque conversión STL (Modelo 1) asociado a simplificación STL y enfoque de ingeniería inversa (Modelo 2). Para el análisis de elementos finitos se utilizó la acción del músculo pterigoideo lateral como condición de carga para evaluar desplazamiento total (D), lo que equivale tensión de von Mises (VM) y la tensión principal máxima (MP). Los dos modelos presentan diferencias en la geometría de la superficie en relación con el número (1834 (modelo 1), 282 (modelo 2)). Se observaron diferencias en la malla de elementos finitos con respecto a número de elemento (30428 nodos/16683 elementos (modelo 1) y 15.801 nodos/8410 elementos (modelo 2)). La D, VM y áreas de tensión MP presentan distribución similar en ambos modelos. Los valores fueron diferentes respecto a los valores máximo y mínimo de D (desde 0 hasta 0,511 mm (modelo 1) y 0 a 0,544 mm (modelo 2), tensión VM (6,36E-04 - 11,4 MPa (modelo 1) y 2,15e-04 - 14,7 MPa (modelo 2) y tensiones MP (-1,43 a 9,14 MPa (modelo 1) y -1,2 a 11,6 MPa (modelo 2)) a partir de dos métodos de modelado de Bio-CAD. La ingeniería inversa presenta una mejor representación anatómica en comparación con el enfoque de conversión STL. Los modelos presentan diferencias en la malla de elementos finitos, el desplazamiento total y la distribución de la tensión.

Inmunogenicidad de proteínas recombinantes comparada con el empleo de herramientas bioinformáticas / Immunogenicity of recombinant proteins compared with the use of bioinformatics tools

Objetivo: para determinar la utilidad de herramientas inmunoinformáticas para detectar péptidos que puedan ser inmunodominantes, y evaluar las diferencias entre las respuestas inmunes de los modelos animales empleados en los estudios preclínicos y en los humanos. Métodos: se modeló la respuesta frente a dos proteínas exógenas: la estreptocinasa recombinante y el antígeno de superficie de la hepatitis B. A partir de sus secuencias primarias se emplearon algoritmos para identificar epítopes B y T frente a moléculas HLA de clase I y II (HLA-A*0201, HLA-DRB1*0301 y HLA-DRB1*0701) y los haplotipos murinos H2-Kd y H2-Kk. Se seleccionaron los péptidos de más alta puntuación. Resultados: el algoritmo ABCPred mostró una mejor capacidad de predicción de epítopes B, mientras fue mayor la coincidencia para los programas de modelación de la respuesta T. Los epítopes generados para el haplotipo H2-Kk tuvieron una similitud mayor con los presentados por las moléculas HLA seleccionadas. Conclusiones: se presenta una metodología aplicable al desarrollo de vacunas de subunidades y multiepitópicas, así como para otros fármacos biotecnológicos de naturaleza peptídica, que permite optimizar las etapas preclínicas y clínicas, a muy bajo costo, mínimos requerimientos tecnológicos, utilización óptima de medios, recursos y capital humano disponibles en cualquier institución del sistema nacional de salud

Objective: determine the usefulness of immunoinformatics tools to detect potentially immunodominant peptides, and evaluate the differences between the immune responses provided by the animal models used in preclinical and human studies. Methods: modeling was conducted of the response to two exogenous proteins: recombinant streptokinase and hepatitis B surface antigen. Based on their primary sequences, algorithms were used to identify B and T epitopes against HLA class I and II molecules (HLA-A*0201, HLA-DRB1*0301 and HLA-DRB1*0701), and murine haplotypes H2-Kd and H2-Kk. The highest scoring peptides were chosen. Results: ABCPred algorithm showed a better prediction capacity for B epitopes, whereas coincidence was greater in modeling programs for the T response. The epitopes generated for haplotype H2-Kk had greater similitude with those presented by the HLA molecules selected. Conclusions: a methodology is presented which is applicable to the development of subunit and multiepitope vaccines, as well as other peptidic biotechnological drugs. This methodology allows optimization of the preclinical and clinical phases at a very low cost, with minimal technological requirements, optimal use of media, and resources and human capital available at any institution of the national health system

Computational Modeling with Fluid-Structure Interaction of the Severe M1 Stenosis Before and After Stenting / 신경중재치료의학

PURPOSE: Image-based computational models with fluid-structure interaction (FSI) can be used to perform plaque mechanical analysis in intracranial artery stenosis. We described a process in FSI study applied to symptomatic severe intracranial (M1) stenosis before and after stenting. MATERIALS AND METHODS: Reconstructed 3D angiography in STL format was transferred to Magics for smoothing of vessel surface and trimming of branch vessels and to HyperMesh for generating tetra volume mesh from triangular surface-meshed 3D angiogram. Computational analysis of blood flow in the blood vessels was performed using the commercial finite element software ADINA Ver 8.5. The distribution of wall shear stress (WSS), peak velocity and pressure was analyzed before and after intracranial stenting. RESULTS: The wall shear stress distributions from Computational fluid dynamics (CFD) simulation with rigid wall assumption as well as FSI simulation before and after stenting could be compared. The difference of WSS between rigid wall and compliant wall model both in pre- and post-stent case is only minor except at the stenosis region. These WSS values were greatly reduced after stenting to 15~20 Pa at systole and 3~5 Pa at end-diastole in CFD simulation, which are similar in FSI simulations. CONCLUSION: Our study revealed that FSI simulation before and after intracranial stenting was feasible despite of limited vessel wall dimension and could reveal change of WSS as well as flow velocity and wall pressure.

Teatro anatômico digital: práticas de representação do corpo na ciência / The digital anatomical theater: scientific practices for representing the body

Investigam-se etnograficamente as práticas de representação do corpo na ciência contemporânea, por meio de uma análise comparativa com o teatro anatômico renascentista, uma prática de conhecimento do corpo nos primórdios da ciência moderna. Busca-se desvendar, sobretudo, de que modo a visualização do interior do corpo atua na produção de conhecimento sobre seu funcionamento. Conclui-se que, contemporaneamente, a produção de saberes privilegia sobremaneira a validação de um código e a modelagem de processos biológicos nos quais se busca intervir. Procura-se, assim, desvendar os sentidos da circulação de imagens, dados e teorias que unem corpos materiais, técnicas de visualização e cientistas, possibilitando, desse modo, a produção de verdades sobre o corpo biológico.

Contemporary scientific practices for representing the body are investigated ethnographically through a comparative analysis with the Renaissance anatomical theater, a practice used to understand the body in early modern science. First and foremost, I seek to reveal the manner in which visualization of the inside of the body produces knowledge of its functioning. The conclusion is that, currently, the production of knowledge greatly privileges the validation of code and modeling of the biological processes in which one wishes to intervene. The objective is to unveil the meaning of the circulation of images, data and theories that bring together material bodies, visualization techniques and scientists, enabling the production of truth about the body in a biological sense.

A novel polar-based human face recognition computational model

Motivated by a recently proposed biologically inspired face recognition approach, we investigated the relation between human behavior and a computational model based on Fourier-Bessel (FB) spatial patterns. We measured human recognition performance of FB filtered face images using an 8-alternative forced-choice method. Test stimuli were generated by converting the images from the spatial to the FB domain, filtering the resulting coefficients with a band-pass filter, and finally taking the inverse FB transformation of the filtered coefficients. The performance of the computational models was tested using a simulation of the psychophysical experiment. In the FB model, face images were first filtered by simulated V1- type neurons and later analyzed globally for their content of FB components. In general, there was a higher human contrast sensitivity to radially than to angularly filtered images, but both functions peaked at the 11.3-16 frequency interval. The FB-based model presented similar behavior with regard to peak position and relative sensitivity, but had a wider frequency band width and a narrower response range. The response pattern of two alternative models, based on local FB analysis and on raw luminance, strongly diverged from the human behavior patterns. These results suggest that human performance can be constrained by the type of information conveyed by polar patterns, and consequently that humans might use FB-like spatial patterns in face processing.

Construcción de modelos computacionales para el análisis de esfuerzos mecánicos de piezas óseas utilizando imágenes de TC: aplicación a la articulación gleno-humeral / Construction of computational models for the stress analysis of the bones using CT imaging: application in the gleno-humeral joint

Se presenta en este trabajo una metodología para el procesamiento de imágenes de estudios de TC para la construcción de modelos computacionales de piezas óseas. Los modelos computacionales son utilizados para el análisis de esfuerzos utilizando el Método de los Elementos Finitos. Las constantes elásticas del tejido óseo son calculadas a partir de los datos de densidad de las TC. La metodología propuesta es aplicada en la construcción de un modelo para el análisis de la articulación gleno-humeral.

A methodology for the construction of computational models from CT images is presented in this work. Computational models serve for the stress analysis of the bones using the Finite Element Method. The elastic constants of the bone tissue are calculated using the density data obtained in from the CTs. The proposed methodology is demonstrated in the construction of a model for the gleno-humeral joint.

Computational Analysis of Tumor Angiogenesis Patterns Using a Two-dimensional Model

Tumor angiogenesis was simulated using a two-dimensional computational model. The equation that governed angiogenesis comprised a tumor angiogenesis factor (TAF) conservation equation in time and space, which was solved numerically using the Galerkin finite element method. The time derivative in the equation was approximated by a forward Euler scheme. A stochastic process model was used to simulate vessel formation and vessel elongation towards a paracrine site, i.e., tumor-secreted basic fibroblast growth factor (bFGF). In this study, we assumed a two-dimensional model that represented a thin (1.0mm) slice of the tumor. The growth of the tumor over time was modeled according to the dynamic value of bFGF secreted within the tumor. The data used for the model were based on a previously reported model of a brain tumor in which four distinct stages (multicellular spherical, first detectable lesion, diagnosis, and death of the virtual patient) were modeled. In our study, computation was not continued beyond the 'diagnosis' time point to avoid the computational complexity of analyzing numerous vascular branches. The numerical solutions revealed that no bFGF remained within the region in which vessels developed, owing to the uptake of bFGF by endothelial cells. Consequently, a sharp declining gradient of bFGF existed near the surface of the tumor. The vascular architecture developed numerous branches close to the tumor surface (the brush-border effect). Asymmetrical tumor growth was associated with a greater degree of branching at the tumor surface.