microRNA-365 attenuated intervertebral disc degeneration through modulating nucleus pulposus cell apoptosis and extracellular matrix degradation by targeting EFNA3.

This present study is aimed to investigate the role of microRNA-365 (miR-365) in the development of intervertebral disc degeneration (IDD). Nucleus pulposus (NP) cells were transfected by miR-365 mimic and miR-365 inhibitor, respectively. Concomitantly, the transfection efficiency and the expression level of miRNA were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Meanwhile, NP cells apoptosis was measured through propidium iodide (PI)-AnnexinV-fluorescein isothiocyanate (FITC) apoptosis detection kit. Subsequently, immunofluorescence (IF) staining was performed to assess the expression of collagen II, aggrecan and matrix metalloproteinase 13 (MMP-13). In addition, bioinformatic prediction and Luciferase reporter assay were used to reveal the target gene of miR-365. Finally, we isolated the primary NP cells from rats and injected NP-miR-365 in rat IDD models. The results showed that overexpression of miR-365 could effectively inhibit NP cells apoptosis and MMP-13 expression and upregulate the expression of collagen II and aggrecan. Conversely, suppression of miR-365 enhanced NP cell apoptosis and elevated MMP-13 expression, but decreased the expression of collagen II and aggrecan. Moreover, the further data demonstrated that miR-365 mediated NP cell degradation through targeting ephrin-A3 (EFNA3). In addition, the cells apoptosis and catabolic markers were increased in NP cells when EFNA3 upregulated. More importantly, the vivo data supported that miR-365-NP cells injection ameliorated IDD in rats models. miR-365 could alleviate the development of IDD by regulating NP cell apoptosis and ECM degradation, which is likely mediated by targeting EFNA3. Therefore, miR-365 may be a promising therapeutic avenue for treatment IDD through EFNA3.

Magnesium malate-modified calcium phosphate bone cement promotes the repair of vertebral bone defects in minipigs via regulating CGRP.

Active artificial bone substitutes are crucial in bone repair and reconstruction. Calcium phosphate bone cement (CPC) is known for its biocompatibility, degradability, and ability to fill various shaped bone defects. However, its low osteoinductive capacity limits bone regeneration applications. Effectively integrating osteoinductive magnesium ions with CPC remains a challenge. Herein, we developed magnesium malate-modified CPC (MCPC). Incorporating 5% magnesium malate significantly enhances the compressive strength of CPC to (6.18 ± 0.49) MPa, reduces setting time and improves disintegration resistance. In vitro, MCPC steadily releases magnesium ions, promoting the proliferation of MC3T3-E1 cells without causing significant apoptosis, proving its biocompatibility. Molecularly, magnesium malate prompts macrophages to release prostaglandin E2 (PGE2) and synergistically stimulates dorsal root ganglion (DRG) neurons to synthesize and release calcitonin gene-related peptide (CGRP). The CGRP released by DRG neurons enhances the expression of the key osteogenic transcription factor Runt-related transcription factor-2 (RUNX2) in MC3T3-E1 cells, promoting osteogenesis. In vivo experiments using minipig vertebral bone defect model showed MCPC significantly increases the bone volume fraction, bone density, new bone formation, and proportion of mature bone in the defect area compared to CPC. Additionally, MCPC group exhibited significantly higher levels of osteogenesis and angiogenesis markers compared to CPC group, with no inflammation or necrosis observed in the hearts, livers, or kidneys, indicating its good biocompatibility. In conclusion, MCPC participates in the repair of bone defects in the complex post-fracture microenvironment through interactions among macrophages, DRG neurons, and osteoblasts. This demonstrates its significant potential for clinical application in bone defect repair.

Dynamical modulation of hypersynchronous seizure onset with transcranial magneto-acoustic stimulation in a hippocampal computational model.

Hypersynchronous (HYP) seizure onset is one of the frequently observed seizure-onset patterns in temporal lobe epileptic animals and patients, often accompanied by hippocampal sclerosis. However, the exact mechanisms and ion dynamics of the transition to HYP seizures remain unclear. Transcranial magneto-acoustic stimulation (TMAS) has recently been proposed as a novel non-invasive brain therapy method to modulate neurological disorders. Therefore, we propose a biophysical computational hippocampal network model to explore the evolution of HYP seizure caused by changes in crucial physiological parameters and design an effective TMAS strategy to modulate HYP seizure onset. We find that the cooperative effects of abnormal glial uptake strength of potassium and excessive bath potassium concentration could produce multiple discharge patterns and result in transitions from the normal state to the HYP seizure state and ultimately to the depolarization block state. Moreover, we find that the pyramidal neuron and the PV+ interneuron in HYP seizure-onset state exhibit saddle-node-on-invariant-circle/saddle homoclinic (SH) and saddle-node/SH at onset/offset bifurcation pairs, respectively. Furthermore, the response of neuronal activities to TMAS of different ultrasonic waveforms revealed that lower sine wave stimulation can increase the latency of HYP seizures and even completely suppress seizures. More importantly, we propose an ultrasonic parameter area that not only effectively regulates epileptic rhythms but also is within the safety limits of ultrasound neuromodulation therapy. Our results may offer a more comprehensive understanding of the mechanisms of HYP seizure and provide a theoretical basis for the application of TMAS in treating specific types of seizures.

Deep learning-based prediction of coronary artery stenosis resistance.

Coronary artery stenosis resistance (SR) is a key factor for noninvasive calculations of fractional flow reserve derived from coronary CT angiography (FFRCT). Existing computational fluid dynamics (CFD) methods, including three-dimensional (3-D) computational and zero-dimensional (0-D) analytical models, are usually limited by high calculation cost or low precision. In this study, we have developed a multi-input back-propagation neural network (BPNN) that can rapidly and accurately predict coronary SR. A training data set including 3,028 idealized anatomic coronary artery stenosis models was constructed for 3-D CFD calculation of SR with specific blood flow boundaries. Based on 3-D calculation results, we established a BPNN whose input is geometric parameters and blood flow, whereas output is SR. Then, a test set (324 cases) was constructed to evaluate the performance of the BPNN model. To verify the validity and practicability of the network, BPNN prediction results were compared with 3-D CFD and 0-D analytical model results from patient-specific models. For test set, the mean square error (MSE) between CFD and prediction results was 2.97%, linear regression analysis indicating a good correlation between the two (P < 0.001). For 30 patient-specific models, the MSE of BPNN and the 0-D model were 3.26 and 9.7%, respectively. The calculation time for BPNN and the 3-D CFD model for 30 cases was about 2.15 s and 2 h, respectively. The present results demonstrate the practicability of using deep learning methods for fast and accurate predictions of coronary artery SR. Our study represents an advance in noninvasive calculations of FFRCT.NEW & NOTEWORTHY This study developed a multi-input back-propagation neural network (BPNN) that can be used to predict coronary artery stenosis resistance by inputting vascular geometric parameters and blood flow. Compared with previous studies, the network developed in this study can accurately and rapidly predict coronary artery stenosis resistance, which can not only meet clinical requirements but also reduce the cost of calculation duration. This study contributes to the noninvasive methods for the numerical calculation of fractional flow reserve derived from coronary CT angiography (FFRCT) and indicates that this technique can potentially be used for evaluating myocardial ischemia.

Effect of the Coronary Arterial Diameter Derived From Coronary Computed Tomography Angiography on Fractional Flow Reserve.

BACKGROUND: Fractional flow reserve (FFR) is considered to be the criterion standard for the clinical diagnosis of functional myocardial ischemia. In this study, we explored the effect of the coronary arterial diameter derived from coronary computed tomography angiography on FFR. METHOD: We retrospectively reviewed the clinical information of 131 patients with moderate coronary artery stenosis. To compare the mean diameter of stenotic vessels, patients were divided into ischemic and nonischemic groups. According to the clinical statistics of the diameter of the ischemic group and the nonischemic group, we established 8 ideal models of coronary artery diameter of 4 mm (40%, 50%, 60%, and 70% stenosis) and diameter of 3 mm (40%, 50%, 60%, and 70% stenosis). Two sets of numerical simulation experiments were carried out: experiment 1 evaluated the variation rate of CT-based computation of non-invasive fractional flow reserve (FFRCT) with vessel diameters of 4 mm and 3 mm under different stenosis rates, and experiment 2 explored the variation of FFRCT with vessel diameters of 4 mm and 3 mm under different cardiac outputs. We simulated changes in the flow of narrow blood vessels by changes in cardiac output. RESULTS: According to clinical statistics, the mean ± SD diameter of stenotic vessels in the ischemic and nonischemic groups was 3.67 ± 0.77 mm and 3.31 ± 0.64 mm (P < 0.05 for difference), respectively. In experiment 1, the FFRCT of coronary with a diameter of 4 mm was 0.86, 0.80, 0.66, and 0.35, and that with a diameter of 3 mm was 0.90, 0.84, 0.71, and 0.50, respectively. In experiment 2, the FFRCT of the coronary vessel diameter of 4 mm was 0.84, 0.80, 0.76, and 0.72, respectively. The FFRCT coronary vessels with a diameter of 3 mm were 0.87, 0.84, 0.80, and 0.76, respectively. CONCLUSIONS: As the stenosis increases, compared with narrow blood vessel of small diameter, the narrow blood vessel with larger diameter is accompanied by faster flow rate changes and is more prone to ischemia.

Comparison of ablation characteristics of three different radiofrequency applicators in renal sympathetic denervation.

OBJECTIVE: Renal sympathetic denervation (RDN) is an alternative treatment for resistant hypertension (RH). This study aims to compare ablation effects using three radiofrequency applicators (i.e., balloon-based four electrodes, spiral and monopolar devices). METHODS: An idealized three-dimensional model of the renal artery was established using COMSOL Multiphysics to mimic radiofrequency ablation (RFA). Radiofrequency (RF) energy was delivered to the tissue at the same simulation settings, i.e., 4, 6, and 8 W for 60 s, using the three abovementioned RF applicators. The temperature distribution in the tissue was calculated using the coupled electrical-thermal-fluid finite element method. Lesion borders were defined using 50 °C isotherms. The maximum lesion depth, width, area, and circumferential coverage rate were compared among the three applicators at a blood flow of 0.4 m/s. Monopolar RF ablations in a renal artery phantom model were performed to validate the reliability of the simulation method. RESULTS: The balloon-based system yields greater lesion depths and widths compared with spiral and monopolar denervation under the same power. The range of maximum lesion depth is 1.58-3.11 mm for balloon-based RDN, 0.90-1.81 mm for spiral RDN and 1.12-2.38 mm for monopolar RDN, at a power of 4-8 W. The corresponding ranges of maximum lesion width are 2.22-5.73, 1.48-3.54, and 1.93-5.31 mm, respectively, and the circumferential coverage rates of the renal artery are 41.43%-91.99%, 31.71%-66.23%, and 9.55%-23.06%, respectively. The average velocity after balloon-based, spiral, and monopolar RDN increases by 3, 5, and 1 cm/s, respectively. The validation of the computer model offered prediction errors are <5% in terms of temperature at different locations (i.e., 2, 4, and 8 mm). CONCLUSIONS: In terms of lesion size, balloon-based RDN appears to be the best option for the treatment of RH. However, the change in flow velocity in the arterial flow field suggests that its hemodynamic changes must be prioritized for investigating its safety. Although spiral catheter ablation yields the smallest lesion size and a significant change in flow velocity in the flow field, its coverage rate is larger than that of monopolar RDN; compared with balloon-based RDN, it did not obstruct most of the blood flow.

Machine Learning Approaches-Driven for Mortality Prediction for Patients Undergoing Craniotomy in ICU.

OBJECTIVES: We aimed to predict the mortality of patients with craniotomy in ICU by using predictive models to extract the high-risk factors leading to the death of patients from a retrospective a study. METHODS: Five machine-learning (ML) algorithms were applied for training on mortality predictive models with the data from a surgical intensive care unit (ICU) database of the Fujian Provincial Hospital in China. The accuracy, precision, recall, f1 score and the area under the receiver operator characteristic curve (AUC) were used to evaluate the performance of different models, and the calibration of the model was evaluated by brier score. RESULTS: We demonstrated that eXtreme Gradient Boosting (XGBoost) was more suitable for the task, demonstrating a AUC of 0.84. We analyzed the feature importance with the Local Interpretable Model-agnostic Explanations (LIME) analysis and further identified the high-risk factors of mortality in ICU through this study. CONCLUSIONS: This study established the mortality predictive model of patients who had undergone craniotomy in ICU. Identification of the factors that had great influence on mortality has the potential to provide auxiliary decision support for clinical medical staff on their practices.

Enhancing the Efficiency of Distraction Osteogenesis through Rate-Varying Distraction: A Computational Study.

Distraction osteogenesis (DO) is a mechanobiological process of producing new bone and overlying soft tissues through the gradual and controlled distraction of surgically separated bone segments. The process of bone regeneration during DO is largely affected by distraction parameters. In the present study, a distraction strategy with varying distraction rates (i.e., "rate-varying distraction") is proposed, with the aim of shortening the distraction time and improving the efficiency of DO. We hypothesized that faster and better healing can be achieved with rate-varying distractions, as compared with constant-rate distractions. A computational model incorporating the viscoelastic behaviors of the callus tissues and the mechano-regulatory tissue differentiation laws was developed and validated to predict the bone regeneration process during DO. The effect of rate-varying distraction on the healing outcomes (bony bridging time and bone formation) was examined. Compared to the constant low-rate distraction, a low-to-high rate-varying distraction provided a favorable mechanical environment for angiogenesis and bone tissue differentiation, throughout the distraction and consolidation phase, leading to an improved healing outcome with a shortened healing time. These results suggest that a rate-varying clinical strategy could reduce the overall treatment time of DO and decrease the risk of complications related to the external fixator.

Evaluating the thermal performance of a balloon-based renal sympathetic denervation system with array electrodes: a finite element study.

Renal denervation transmits radiofrequency (RF) energy through an electrode to treat resistant hypertension (RH), applying ablation in the renal artery. Several experimental studies have shown that this treatment has been used effectively to treat RH. The aim of this paper is to investigate the effect of ablation parameters (i.e., electrode length, applied voltage, ablation time, and blood flow) on the temperature distribution using a balloon-based array electrodes system. A simplified three-dimensional model including four electrodes and a balloon was established. The balloon diameter was 3 mm and placed in a 5 mm diameter renal artery for forming intra-arterial occlusion. Four electrodes were mounted on the balloon and distributed in the same plane to mimic circumferential RF ablation. Computer simulations were conducted to investigate the thermal performances of the device by setting different electrode configurations, treatment protocols, and physiological factors. The thermal performances including the thermal distribution, maximum lesion depth, length, and area were analyzed. The lesion shape of the array RF electrodes was approximately a sphere with a 100% circumference coverage rate of the renal artery. The lesion depth and length increase with each factor except for blood velocity. Increasing the electrode length from 2 to 4 mm or 2 to 6 mm, the lesion depth increases by 1.15 mm and 0.54 mm at 60 s. The corresponding lesion length increases by 2.65 mm and 2.34 mm, respectively. The range of effective lesion depth is 1.90-4.90 mm, at a voltage of 15-30 V. But the peak temperature at the arterial outer wall exceeded 100 °C when the voltage is above 25 V. In tissue, the degree of thermal injury in the 2 mm area reached 100%, but in blood was not more than 5%. There was no significant difference at different flow conditions because the difference value in lesion depth was not exceeded 0.5 mm. The results showed that the balloon-based four electrodes system is expected to overcome the difficulty of incomplete ablation. In clinical application, 2 mm-electrode is recommended to avoid long wall damage as much as possible and control the voltage below 25 V. This treatment has little thermal injury on the blood, which means it may avoid coagulation formation. Moreover, the application of this device does not need to consider the difference in individual blood velocity.

Comparison of Instantaneous Wave-Free Ratio (iFR) and Fractional Flow Reserve (FFR) with respect to Their Sensitivities to Cardiovascular Factors: A Computational Model-Based Study.

While coronary revascularization strategies guided by instantaneous wave-free ratio (iFR) are, in general, noninferior to those guided by fractional flow reserve (FFR) with respect to the rate of major adverse cardiac events at one-year follow-up in patients with stable angina or an acute coronary syndrome, the overall accuracy of diagnosis with iFR in large patient cohorts is about 80% compared with the diagnosis with FFR. So far, it remains incompletely understood what factors contribute to the discordant diagnosis between iFR and FFR. In this study, a computational method was used to systemically investigate the respective effects of various cardiovascular factors on FFR and iFR. The results showed that deterioration in aortic valve disease (e.g., regurgitation or stenosis) led to a marked decrease in iFR and a mild increase in FFR given fixed severity of coronary artery stenosis and that increasing coronary microvascular resistance caused a considerable increase in both iFR and FFR, but the degree of increase in iFR was lower than that in FFR. These findings suggest that there is a high probability of discordant diagnosis between iFR and FFR in patients with severe aortic valve disease or coronary microcirculation dysfunction.

[Application of hemodynamic optimization in the design of artificial heart].

Heart failure is one kind of cardiovascular disease with high risk and high incidence. As an effective treatment of heart failure, artificial heart is gradually used in clinical treatment. Blood compatibility is an important parameter or index of artificial heart, and how to evaluate it through hemodynamic design and in vitro hemolysis test is a research hotspot in the industry. This paper first reviews the research progress in hemodynamic optimization and in vitro hemolysis evaluation of artificial heart, and then introduces the research achievements and progress of the team in related fields. The hemodynamic performance of the blood pump optimized in this paper can meet the needs of use. The normalized index of hemolysis obtained by in standard vitro hemolysis test is less than 0.1 g/100 L, which has good hemolysis performance in vitro. The optimization method described in this paper is suitable for most of the development of blood pump and can provide reference for related research work.

Hemodynamic effects of enhanced external counterpulsation on cerebral arteries: a multiscale study.

BACKGROUND: Enhanced external counterpulsation (EECP) is an effective method for treating patients with cerebral ischemic stroke, while hemodynamics is the major contributing factor in the treatment of EECP. Different counterpulsation modes have the potential to lead to different acute and long-term hemodynamic changes, resulting in different treatment effects. However, various questions about appropriate counterpulsation modes for optimizing hemodynamic effects remain unanswered in clinical treatment. METHODS: A zero-dimensional/three-dimensional (0D/3D) geometric multiscale model of the cerebral artery was established to obtain acute hemodynamic indicators, including mean arterial pressure (MAP) and cerebral blood flow (CBF), as well as localized hemodynamic details for the cerebral artery, which includes wall shear stress (WSS) and oscillatory shear index (OSI). Counterpulsation was achieved by applying pressure on calf, thigh and buttock modules in the 0D model. Different counterpulsation modes including various pressure amplitudes and pressurization durations were applied to investigate hemodynamic responses, which impact acute and long-term treatment effects. Both vascular collapse and cerebral autoregulation were considered during counterpulsation. RESULTS: Variations of pressure amplitude and pressurization duration have different impacts on hemodynamic effects during EECP treatment. There were small differences in the hemodynamics when similar or different pressure amplitudes were applied to calves, thighs and buttocks. When increasing pressure amplitude was applied to the three body parts, MAP and CBF improved slightly. When pressure amplitude exceeded 200 mmHg, hemodynamic indicators almost never changed, demonstrating consistency with clinical data. However, hemodynamic indicators improved significantly with increasing pressurization duration. For pressurization durations of 0.5, 0.6 and 0.7 s, percentage increases for MAP during counterpulsation were 1.5%, 23.5% and 39.0%, for CBF were 1.2%, 23.4% and 41.6% and for time-averaged WSS were 0.2%, 43.5% and 85.0%, respectively. CONCLUSIONS: When EECP was applied to patients with cerebral ischemic stroke, pressure amplitude applied to the three parts may remain the same. Patients may not gain much more benefit from EECP treatment by excessively increasing pressure amplitude above 200 mmHg. However, during clinical procedures, pressurization duration could be increased to 0.7 s during the cardiac circle to optimize the hemodynamics for possible superior treatment outcomes.

On the relationship between competitive flow and FFT analysis of the flow waves in the left internal mammary artery graft in the process of CABG.

BACKGROUND: During coronary artery bypass grafting (CABG), the ratio of powers of the fundamental frequency and its first harmonic (F0/H1) in fast Fourier transformation (FFT) analysis of the graft's flow waves has been used in the field of evaluation of the patency in anastomosis. But there is no report about using the FFT method to evaluate the magnitude of competitive flow. This study is aiming at exploring the relationship between competitive flow and FFT analysis of the flow waves in left internal mammary artery (LIMA) graft, and finding a new method to evaluate the magnitude of competitive flow. METHODS: At first, establishing the CABG multiscale models of different stenosis in left anterior descending artery (LAD) to get different magnitude of competitive flows. Then, calculating the models by ANSYS-CFX and getting the flow waves in LIMA. Finally, analyzing the flow waves by FFT method and comparing the FFT results with the magnitude of competitive flow. RESULTS: There is no relationship between competitive flow and F0/H1. As for F0/H2 and F0/H3, they both increase with the reduction of the stenosis in LAD. But the increase of F0/H3 is not obviously enough and it can't identify the significant competitive flow clearly, so it can't be used as the evaluation index. It is found that F0/H2 increases obviously with the increase of the competitive flow and can identify the significant competitive flow. CONCLUSION: The FFT method can be used in the evaluation of competitive flow and the F0/H2 is the ideal index. High F0/H2 refers to the significant competitive flow. This method can be used during CABG to avoid the risk of competitive flow.

Hemodynamic analysis of sequential graft from right coronary system to left coronary system.

BACKGROUND: Sequential and single grafting are two surgical procedures of coronary artery bypass grafting. However, it remains unclear if the sequential graft can be used between the right and left coronary artery system. The purpose of this paper is to clarify the possibility of right coronary artery system anastomosis to left coronary system. METHODS: A patient-specific 3D model was first reconstructed based on coronary computed tomography angiography (CCTA) images. Two different grafts, the normal multi-graft (Model 1) and the novel multi-graft (Model 2), were then implemented on this patient-specific model using virtual surgery techniques. In Model 1, the single graft was anastomosed to right coronary artery (RCA) and the sequential graft was adopted to anastomose left anterior descending (LAD) and left circumflex artery (LCX). While in Model 2, the single graft was anastomosed to LAD and the sequential graft was adopted to anastomose RCA and LCX. A zero-dimensional/three-dimensional (0D/3D) coupling method was used to realize the multi-scale simulation of both the pre-operative and two post-operative models. RESULTS: Flow rates in the coronary artery and grafts were obtained. The hemodynamic parameters were also showed, including wall shear stress (WSS) and oscillatory shear index (OSI). The area of low WSS and OSI in Model 1 was much less than that in Model 2. CONCLUSIONS: Model 1 shows optimistic hemodynamic modifications which may enhance the long-term patency of grafts. The anterior segments of sequential graft have better long-term patency than the posterior segments. With rational spatial position of the heart vessels, the last anastomosis of sequential graft should be connected to the main branch.

Comparative experiments on phantom and ex vivo liver tissue in microwave ablation.

PURPOSE: The aim of this study is to investigate the thermal field distribution of phantom and ex vivo liver tissue in microwave ablation. We intent to verify if the phantom can be used in future studies in lieu of actual tissue. METHODS: This experiment was divided into two groups of phantom and ex vivo porcine liver tissue. 2450 MHz is set. The tests last up to 240 s in 60 W. The velocity of the circulating water pumps were adjusted to 40 rounds/min. Twenty-five copper-constantan thermocouples (TCs) were inserted at the specified position to record temperature data. RESULT: For the cooling water, the temperature field was non-symmetric distribution at the gap before (z > z < 0 mm) of two groups of experiments. At the part without cooling water (z > 0 mm), effective ablation areas were larger; near the microwave antenna, the temperature curves showed good consistency for both materials. Far away from the microwave antenna, the value difference increased between phantom and liver tissue. Moreover, the effect of cooling water in phantom is more obvious than it in liver tissue. The shapes of ablation areas from two groups are not same. CONCLUSION: The result of the present work implied that heating patterns of liver tissue and phantom are comparable. But the difference of temperature field between two kinds of materials cannot be ignored. In cases of using phantom to verify temperature field in lieu of actual tissue, the researchers should pay full attention to these difference points.

A real-time patient-specific treatment strategy for enhanced external counterpulsation.

Diastolic/systolic blood pressure ratio (D/S) ≥ 1.2 is the gold standard of enhanced external counterpulsation (EECP) treatment, but it does not show a clear clinical correspondence with the configuration of the EECP mode. As such, a single target results in different treatment effects in different individuals. The local haemodynamic effect (wall shear stress, WSS) of EECP on vascular endothelial cells is conducive to promote the growth of collateral circulation vessels and restore the blood supply distal to the stenosis lesion. Considering the haemodynamic effects of WSS on human arteries, this study developed a real-time patient-specific treatment strategy of EECP for patients with cardio-cerebrovascular diseases. Based on patient-specific haemodynamic data from 113 individuals, an optimization algorithm was developed to achieve the individualization of a 0D lumped-parameter model of the human circulatory system, thereby simulating the patient-specific global haemodynamic effects. 0D/3D coupled cardio-cerebrovascular models of two subjects were established to simulate the local WSS. We then established statistical models to evaluate clinically unmeasurable WSS based on measurable global haemodynamic indicators. With the aim of attaining appropriate area- and time-averaged WSS (ATAWSS, 4-7 Pa), as evaluated by global haemodynamic indicators, a closed-loop feedback tuning method was developed to provide patient-specific EECP treatment strategies. Results showed that for clinical data collected from 113 individuals, the individualized 0D model can accurately simulate patient-specific global haemodynamic effects (average error <5%). Based on two subjects, the statistical models can be used to evaluate local ATAWSS (error <6%) for coronary arteries and for cerebral arteries. An EECP mode planned by the patient-specific treatment strategy can promote an appropriate ATAWSS within a 16 s calculation time. The real-time patient-specific treatment strategy of EECP is expected to improve the long-term outcome for each patient and have potential clinical significance.

Examining the low-voltage fast seizure-onset and its response to optogenetic stimulation in a biophysical network model of the hippocampus.

Low-voltage fast (LVF) seizure-onset is one of the two frequently observed temporal lobe seizure-onset patterns. Depth electroencephalogram profile analysis illustrated that the peak amplitude of LVF onset was deep temporal areas, e.g., hippocampus. However, the specific dynamic transition mechanisms between normal hippocampal rhythmic activity and LVF seizure-onset remain unclear. Recently, the optogenetic approach to gain control over epileptic hyper-excitability both in vitro and in vivo has become a novel noninvasive modulation strategy. Here, we combined biophysical modeling to study LVF dynamics following changes in crucial physiological parameters, and investigated the potential optogenetic intervention mechanism for both excitatory and inhibitory control. In an Ammon's horn 3 (CA3) biophysical model with light-sensitive protein channelrhodopsin 2 (ChR2), we found that the cooperative effects of excessive extracellular potassium concentration of parvalbumin-positive (PV+) inhibitory interneurons and synaptic links could induce abundant types of discharges of the hippocampus, and lead to transitions from gamma oscillations to LVF seizure-onset. Simulations of optogenetic stimulation revealed that the LVF seizure-onset and morbid fast spiking could not be eliminated by targeting PV+ neurons, whereas the epileptic network was more sensitive to the excitatory control of principal neurons with strong optogenetic currents. We illustrate that in the epileptic hippocampal network, the trajectories of the normal and the seizure state are in close vicinity and optogenetic perturbations therefore may result in transitions. The network model system developed in this study represents a scientific instrument to disclose the underlying principles of LVF, to characterize the effects of optogenetic neuromodulation, and to guide future treatment for specific types of seizures.

The fourth species of Leptobrachella (Anura, Megophryidae) found at Shiwandashan National Nature Reserve, Guangxi, China.

A new species of the genus Leptobrachella, L.guinanensissp. nov., is described in this study based on morphological, molecular, and bioacoustic data. The species was discovered in the Shiwandashan National Nature Reserve in Shangsi County, Guangxi, China. Phylogenetically, L.guinanensissp. nov. is closely related to L.ventripunctata. However, there are distinct morphological differences between L.guinanensissp. nov. and L.ventripunctata, as well as three other sympatric species (L.shangsiensis, L.shiwandashanensis, and L.sungi). These differences include body size (SVL 30.5-32.5 mm in males; 38.7-41.8 mm in females in the new species vs 25.5-28.0 mm in males, 31.5-35.0 mm in females in L.ventripunctata), the absence of brown spots on the ventral surface (vs chest and belly creamy white with many scattered brown spots in L.ventripunctata), 1/3 toe webbing and wide toe lateral fringes (vs no toe webbing and no lateral fringes in L.ventripunctata), and distinct dermal ridges under toes (vs absent in L.ventripunctata). Furthermore, the dominant vocal frequencies of the new species range from 7.3 to 8.3 kHz, which is unique compared to other Leptobrachella species and represents the highest dominant frequencies ever recorded. The Shiwandashan National Nature Reserve is now home to four known sympatric species of Leptobrachella.

A comprehensive approach to prediction of fractional flow reserve from deep-learning-augmented model.

The underuse of invasive fractional flow reserve (FFR) in clinical practice has motivated research towards non-invasive prediction of FFR. Although the non-invasive derivation of FFR (FFRCT) using computational fluid dynamics (CFD) principles has become a common practice, its clinical application has been limited due to the considerable time required for computation of resulting changes in haemodynamic conditions. An alternative to CFD technology is incorporating a neural network into the computational process to reduce the time necessary for running an effective model. In this study we propose a cascade of data-driven and physic-based neural networks (DP-NN) for predicting FFR (DL-FFRCT). The first network of cascade network DP-NN includes geometric features, and the second network includes physical features. We compare the differences between data-driven neural network (D-NN) and DP-NN for predicting FFR. The training and testing datasets were obtained by solving the three-dimensional incompressible Navier-Stokes equations. Coronary flow and geometric features were used as inputs to train D-NN. In DP-NN the training process involves first training a D-NN to output resting ΔP as one input feature to the DP-NN. Secondly, the physics-based microcirculatory resistance as another input feature to the DP-NN. Using clinically measured FFR as the "gold standard", we validated the computational accuracy of DL-FFRCT in 77 patients. Compared to D-NN, DP-NN improved the prediction of ΔP (R2 = 0.87 vs. R2 = 0.92). Statistical analysis demonstrated that the diagnostic accuracy of DL-FFRCT was not inferior to FFRCT (85.71 % vs. 88.3 %) and the computational time was reduced by a factor of approximately 3000 (4.26 s vs. 3.5 h). DP-NN represents a near real-time, interpretable, and highly accurate deep-learning network, which contributes to the development of high-performance computational methods for haemodynamics. We anticipate that DP-NN will enable near real-time prediction of DL-FFRCT in personalized narrow blood vessels and provide guidance for cardiovascular disease treatments.

The Effect of Transverse Sinus Stenosis Caused by Arachnoid Granulation on Patients with Venous Pulsatile Tinnitus: A Multiphysics Interaction Simulation Investigation.

This study aimed to investigate the effect of the transverse sinus (TS) stenosis (TSS) position caused by arachnoid granulation on patients with venous pulsatile tinnitus (VPT) and to further identify the types of TSS that are of therapeutic significance for patients. Multiphysics interaction models of six patients with moderate TSS caused by arachnoid granulation and virtual stent placement in TSS were reconstructed, including three patients with TSS located in the middle segment of the TS (group 1) and three patients with TTS in the middle and proximal involvement segment of the TS (group 2). The transient multiphysics interaction simulation method was applied to elucidate the differences in biomechanical and acoustic parameters between the two groups. The results revealed that the blood flow pattern at the TS and sigmoid sinus junction was significantly changed depending on the stenosis position. Preoperative patients had increased blood flow in the TSS region and TSS downstream where the blood flow impacted the vessel wall. In group 1, the postoperative blood flow pattern, average wall pressure, vessel wall vibration, and sound pressure level of the three patients were comparable to the preoperative state. However, the postoperative blood flow velocity decreased in group 2. The postoperative average wall pressure, vessel wall vibration, and sound pressure level of the three patients were significantly improved compared with the preoperative state. Intravascular intervention therapy should be considered for patients with moderate TSS caused by arachnoid granulations in the middle and proximal involvement segment of the TS. TSS might not be considered the cause of VPT symptoms in patients with moderate TSS caused by arachnoid granulation in the middle segment of the TS.