Machine learning-driven predictions and interventions for cardiovascular occlusions.

BACKGROUND: Cardiovascular diseases remain a leading cause of global morbidity and mortality, with heart attacks and strokes representing significant health challenges. The accurate, early diagnosis and management of these conditions are paramount in improving patient outcomes. The specific disease, cardiovascular occlusions, has been chosen for the study due to the significant impact it has on public health. Cardiovascular diseases are a leading cause of mortality globally, and occlusions, which are blockages in the blood vessels, are a critical factor contributing to these conditions. OBJECTIVE: By focusing on cardiovascular occlusions, the study aims to leverage machine learning to improve the prediction and management of these events, potentially helping to reduce the incidence of heart attacks, strokes, and other related health issues. The use of machine learning in this context offers the promise of developing more accurate and timely interventions, thus improving patient outcomes. METHODS: We analyze diverse datasets to assess the efficacy of various machine learning algorithms in predicting heart attacks and strokes, comparing their performance to pinpoint the most accurate and reliable models. Additionally, we classify individuals by their predicted risk levels and examine key features that correlate with the incidence of cardiovascular events. The PyCaret machine learning library's Classification Module was key in developing predictive models which were evaluated with stratified cross-validation for reliable performance estimates. RESULTS: Our findings suggest that machine learning can significantly improve the prediction accuracy for heart attacks and strokes, facilitating earlier and more precise interventions. We also discuss the integration of machine learning models into clinical practice, addressing potential challenges and the need for healthcare professionals to interpret and apply these predictions effectively. CONCLUSIONS: The use of machine learning for risk stratification and the identification of modifiable factors may empower preemptive approaches to cardiovascular care, ultimately aiming to reduce the occurrence of life-threatening events and improve long-term patient health trajectories.

Crown ether decorated silicon photonics for safeguarding against lead poisoning.

Lead (Pb2+) toxification is a concerning, unaddressed global public health crisis that leads to 1 million deaths annually. Yet, public policies to address this issue have fallen short. This work harnesses the unique abilities of crown ethers, which selectively bind to specific ions. This study demonstrates the synergistic integration of highly-scalable silicon photonics, with crown ether amine conjugation via Fischer esterification in an environmentally-friendly fashion. This realizes an integrated photonic platform that enables the in-operando, highly-selective and quantitative detection of various ions. The development dispels the existing notion that Fischer esterification is restricted to organic compounds, facilitating the subsequent amine conjugation for various crown ethers. The presented platform is specifically engineered for selective Pb2+ detection, demonstrating a large dynamic detection range, and applicability to field samples. The compatibility of this platform with cost-effective manufacturing indicates the potential for pervasive implementation of the integrated photonic sensor technology to safeguard against societal Pb2+ poisoning.

Transformative Potential of AI in Healthcare: Definitions, Applications, and Navigating the Ethical Landscape and Public Perspectives.

Artificial intelligence (AI) has emerged as a crucial tool in healthcare with the primary aim of improving patient outcomes and optimizing healthcare delivery. By harnessing machine learning algorithms, natural language processing, and computer vision, AI enables the analysis of complex medical data. The integration of AI into healthcare systems aims to support clinicians, personalize patient care, and enhance population health, all while addressing the challenges posed by rising costs and limited resources. As a subdivision of computer science, AI focuses on the development of advanced algorithms capable of performing complex tasks that were once reliant on human intelligence. The ultimate goal is to achieve human-level performance with improved efficiency and accuracy in problem-solving and task execution, thereby reducing the need for human intervention. Various industries, including engineering, media/entertainment, finance, and education, have already reaped significant benefits by incorporating AI systems into their operations. Notably, the healthcare sector has witnessed rapid growth in the utilization of AI technology. Nevertheless, there remains untapped potential for AI to truly revolutionize the industry. It is important to note that despite concerns about job displacement, AI in healthcare should not be viewed as a threat to human workers. Instead, AI systems are designed to augment and support healthcare professionals, freeing up their time to focus on more complex and critical tasks. By automating routine and repetitive tasks, AI can alleviate the burden on healthcare professionals, allowing them to dedicate more attention to patient care and meaningful interactions. However, legal and ethical challenges must be addressed when embracing AI technology in medicine, alongside comprehensive public education to ensure widespread acceptance.

Correction: Rockman et al. Cell-Based Manufacturing Technology Increases Antigenic Match of Influenza Vaccine and Results in Improved Effectiveness. Vaccines 2023, 11, 52.

The authors would like to make the following corrections to this published paper [...].

Understanding Traumatic Brain Injuries in Military Personnel: Investigating the Dynamic Interplay of the Cerebrospinal Fluid and Brain During Blasts.

Background It is estimated that around 450,000 traumatic brain injury cases have occurred in the 21st century with possible under-reporting. Computational simulations are increasingly used to study the pathophysiology of traumatic brain injuries among US military personnel. This approach allows for investigation without ethical concerns surrounding live subject testing. Methodology The pertinent data on head acceleration is applied to a detailed 3D model of a patient-specific head, which encompasses all significant components of the brain and its surrounding fluid. The use of finite element analysis and smoothed-particle hydrodynamics serves to replicate the interaction between these elements during discharge through simulation of their fluid-structure dynamics. Results The stress levels of the brain are assessed at varying time intervals subsequent to the explosion. The regions where there is an intersection between the skull and brain are observed, along with the predominant orientations in which displacement of the brain occurs resulting in a brain injury. Conclusions It has been determined that the cerebrospinal fluid is inadequate in preventing brain damage caused by multiple abrupt directional shifts of the head. Accordingly, additional research must be undertaken to enhance our comprehension of the injury mechanisms linked with consecutive changes in acceleration impacting the head.

The Impact of Left Ventricular Assist Device Outflow Graft Positioning on Aortic Hemodynamics: Improving Flow Dynamics to Mitigate Aortic Insufficiency.

Heart failure is a global health concern with significant implications for healthcare systems. Left ventricular assist devices (LVADs) provide mechanical support for patients with severe heart failure. However, the placement of the LVAD outflow graft within the aorta has substantial implications for hemodynamics and can lead to aortic insufficiency during long-term support. This study employs computational fluid dynamics (CFD) simulations to investigate the impact of different LVAD outflow graft locations on aortic hemodynamics. The introduction of valve morphology within the aorta geometry allows for a more detailed analysis of hemodynamics at the aortic root. The results demonstrate that the formation of vortex rings and subsequent vortices during the high-velocity jet flow from the graft interacted with the aortic wall. Time-averaged wall shear stress (TAWSS) and oscillatory shear index (OSI) indicate that modification of the outflow graft location changes mechanical states within the aortic wall and aortic valve. Among the studied geometric factors, both the height and inclination angle of the LVAD outflow graft are important in controlling retrograde flow to the aortic root, while the azimuthal angle primarily determines the rotational direction of blood flow in the aortic arch. Thus, precise positioning of the LVAD outflow graft emerges as a critical factor in optimizing patient outcomes by improving the hemodynamic environment.

Haemodynamic changes in visceral hybrid repairs of type III and type V thoracoabdominal aortic aneurysms.

The visceral hybrid procedure combining retrograde visceral bypass grafting and completion endovascular stent grafting is a feasible alternative to conventional open surgical or wholly endovascular repairs of thoracoabdominal aneurysms (TAAA). However, the wide variability in visceral hybrid configurations means that a priori prediction of surgical outcome based on haemodynamic flow profiles such as velocity pattern and wall shear stress post repair remain challenging. We sought to appraise the clinical relevance of computational fluid dynamics (CFD) analyses in the setting of visceral hybrid TAAA repairs. Two patients, one with a type III and the other with a type V TAAA, underwent successful elective and emergency visceral hybrid repairs, respectively. Flow patterns and haemodynamic parameters were analysed using reconstructed pre- and post-operative CT scans. Both type III and type V TAAAs showed highly disturbed flow patterns with varying helicity values preoperatively within their respective aneurysms. Low time-averaged wall shear stress (TAWSS) and high endothelial cell action potential (ECAP) and relative residence time (RRT) associated with thrombogenic susceptibility was observed in the posterior aspect of both TAAAs preoperatively. Despite differing bypass configurations in the elective and emergency repairs, both treatment options appear to improve haemodynamic performance compared to preoperative study. However, we observed reduced TAWSS in the right iliac artery (portending a theoretical risk of future graft and possibly limb thrombosis), after the elective type III visceral hybrid repair, but not the emergency type V repair. We surmise that this difference may be attributed to the higher neo-bifurcation of the aortic stent graft in the type III as compared to the type V repair. Our results demonstrate that CFD can be used in complicated visceral hybrid repair to yield potentially actionable predictive insights with implications on surveillance and enhanced post-operative management, even in patients with complicated geometrical bypass configurations.

Fluid-structure interaction analysis of amniotic fluid with fetus and placenta inside uterus exposed to military blasts.

INTRODUCTION: Pregnancy-related trauma is one of the leading causes of morbidity and mortality in pregnant women and fetuses. The fetal response to injury is largely dependent on the timing of fetal presentation and the underlying pathophysiology of the trauma. The optimal management of pregnant patients who have suffered an obstetric emergency depends on clinical assessment and understanding of the placental implantation process, which can be difficult to perform during an emergency. Understanding the mechanisms of traumatic injuries to the fetus is crucial for developing next-generation protective devices. METHODS: This study aimed to investigate the effect of amniotic fluid on mine blast on the uterus, fetus, and placenta via computational analysis. Finite element models were developed to analyze the effects of explosion forces on the uterus, fetus, and placenta, based on cadaveric data obtained from the literature. This study uses computational fluid-structure interaction simulations to study the effect of external loading on the fetus submerged in amniotic fluid inside of the uterus. RESULTS: Computational fluid-structure interaction simulations are used to study the effect of external loading on the fetus/placenta submerged in amniotic fluid inside the uterus. Cushioning function of the amniotic fluid on the fetus and placenta is demonstrated. The mechanism of traumatic injuries to the fetus/placenta is shown. DISCUSSION: The intention of this research is to understand the cushioning function of the amniotic fluid on the fetus. Further, it is important to make use of this knowledge in order to ensure the safety of pregnant women and their fetuses.

Biventricular biaxial mechanical testing and constitutive modelling of fetal porcine myocardium passive stiffness.

The evaluation of fetal heart mechanical function is becoming increasingly important for determining the prognosis and making subsequent decisions on the treatment and management of congenital heart diseases. Finite Element (FE) modelling can potentially provide detailed information on fetal hearts, and help perform virtual interventions to assist in predicting outcomes and supporting clinical decisions. Previous FE studies have enabled an improved understanding of healthy and diseased fetal heart biomechanics. However, to date, the mechanical properties of the fetal myocardium have not been well characterized which limits the reliability of such modelling. Here, we characterize the passive mechanical properties of late fetal and neonatal porcine hearts via biaxial mechanical testing as a surrogate for human fetal heart mechanical properties. We used samples from both the right and left ventricles over the late gestational period from 85 days of gestation to birth. Constitutive modelling was subsequently performed with a transversely isotropic Fung-type model and a Humphrey-type model, using fiber orientations identified with histology. We found no significant difference in mechanical stiffness across all age groups and between the right and left ventricular samples. This was likely due to the similarity in LV and RV pressures in the fetal heart, and similar gestational maturity across these late gestational ages. We thus recommend using the constitutive model for the average stress-stress behaviour of the tissues in future modelling work. Furthermore, we characterized the variability of the stiffness to inform such work.

A novel coating method to reduce membrane infolding through pre-crimping of covered stents - Computational and experimental evaluation.

A covered stent has been used to treat carotid artery stenosis to reduce the chance of embolization, as it offers improved performance over bare-metal stents. However, membrane infolding of covered stents can affect efficiency and functionality for treating occlusive disease of first-order aortic branches. In order to mitigate the degree of infolding of the stent once it was re-expanded, we proposed a new coating method performed on the pre-crimped stent. A systematic study was carried out to evaluate this new coating technique: a) in vivo animal testing to determine the degree of membrane infolding; b) structural finite element modeling and simulation were used to evaluate the mechanical performance of the covered stent; and c) computational fluid dynamics (CFD) to evaluate hemodynamic behavior of the stents and risk of thrombosis after stent deployment. The degree of infolding was substantially reduced as demonstrated by the in vivo deployment of the pre-crimped stent compared to a conventional dip-coated stent. The structural analysis results demonstrated that the membrane of the covered stent manufactured by conventional dip-coating resulted in a large degree of infolding but this could be minimized by our new pre-crimped coating method. CFD studies showed that the new coating method reduced the risk of thrombosis compared to the conventional coating method. In conclusion, both simulation and in vivo testing demonstrate that our new pre-crimped coating method reduces membrane infolding compared with the conventional dip-coating method and may reduce risk of thrombosis.

Enantiomeric Separation of Racemic Mixtures Using Chiral-Selective and Organic-Solvent-Resistant Thin-Film Composite Membranes.

Membrane-based chiral separation has emerged as a promising method for the efficient separation of chiral molecules. Ideally, the membranes should be able to achieve good enantioselectivity, while maintaining high stability in harsh solvents. However, engineering membranes for chiral molecular separation in harsh organic solvent environments is still a big challenge. In this study, we fabricated a novel thin-film composite nanofiltration membrane composed of (2-hydroxypropyl)-beta-cyclodextrin (HP-ß-CD) as the chiral selector for the enantiomeric separation of racemic 1-phenylethanol chiral compounds in organic solvents. The fabricated membrane achieved 60-80% enantioselectivity of R-phenylethanol over S-phenylethanol in nonpolar n-hexane. It was found that HP-ß-CD played a critical role in the enantioselective performance, as the membrane without HP-ß-CD showed no chiral selectivity. Molecular docking calculations substantiate the experiments by showing that the average free binding energy of S-phenylethanol with HP-ß-CD is stronger than that of R-phenylethanol, indicating that the complex of S-phenylethanol with HP-ß-CD has a higher thermodynamic stability and greater interaction. Furthermore, the crosslinked network between HP-ß-CD and the polyamide layer conferred the membrane with solvent stability in nonpolar solvents. Moreover, this new membrane exhibited good solvent permeance and a molecular weight cutoff of around 650 g mol-1.

Cell-Based Manufacturing Technology Increases Antigenic Match of Influenza Vaccine and Results in Improved Effectiveness.

To ensure that vaccination offers the best protection against an infectious disease, sequence identity between the vaccine and the circulating strain is paramount. During replication of nucleic acid, random mutations occur due to the level of polymerase fidelity. In traditional influenza vaccine manufacture, vaccine viruses are propagated in fertilized chicken eggs, which can result in egg-adaptive mutations in the antigen-encoding genes. Whilst this improves infection and replication in eggs, mutations may reduce the effectiveness of egg-based influenza vaccines against circulating human viruses. In contrast, egg-adaptive mutations are avoided when vaccine viruses are propagated in Madin-Darby canine kidney (MDCK) cell lines during manufacture of cell-based inactivated influenza vaccines. The first mammalian cell-only strain was included in Flucelvax® Quadrivalent in 2017. A sequence analysis of the viruses selected for inclusion in this vaccine (n = 15 vaccine strains, containing both hemagglutinin and neuraminidase) demonstrated that no mutations occur in the antigenic sites of either hemagglutinin or neuraminidase, indicating that cell adaptation does not occur during production of this cell-based vaccine. The development of this now entirely mammalian-based vaccine system, which incorporates both hemagglutinin and neuraminidase, ensures that the significant protective antigens are equivalent to the strains recommended by the World Health Organization (WHO) in both amino acid sequence and glycosylation pattern. The inclusion of both proteins in a vaccine may provide an advantage over recombinant vaccines containing hemagglutinin alone. Findings from real world effectiveness studies support the use of cell-based influenza vaccines.

Addressing Discrepancies between Experimental and Computational Procedures.

Imaging subject-specific heart valve, a crucial step to its design, has experimental variables that if unaccounted for, may lead to erroneous computational analysis and geometric errors of the resulting model. Preparation methods are developed to mitigate some sources of the geometric error. However, the resulting 3D geometry often does not retain the original dimensions before excision. Inverse fluid-structure interaction analysis is used to analyze the resulting geometry and to assess the valve's closure. Based on the resulting closure, it is determined if the geometry used can yield realistic results. If full closure is not reached, the geometry is adjusted adequately until closure is observed.

Potency Testing of Venoms and Antivenoms in Embryonated Eggs: An Ethical Alternative to Animal Testing.

Venoms are complex mixtures of biologically active molecules that impact multiple physiological systems. Manufacture of antivenoms (AVs) therefore requires potency testing using in vivo models to ensure AV efficacy. As part of ongoing research to replace small animals as the standard model for AV potency testing, we developed an alternate in vivo method using the embryonated egg model (EEM). In this model, the survival of chicken embryos envenomated in ovo is determined prior to 50% gestation, when they are recognized as animals by animal welfare legislation. Embryos were found to be susceptible to a range of snake, spider, and marine venoms. This included funnel-web spider venom for which the only other vertebrate, non-primate animal model is newborn mice. Neutralization of venom with standard AV allowed correlation of AV potency results from the EEM to results from animal assays. Our findings indicate that the EEM provides an alternative, insensate in vivo model for the assessment of AV potency. The EEM may enable reduction or replacement of the use of small animals, as longer-term research that enables the elimination of animal use in potency testing continues.

Cross-Linked Polycarbonate Microfiltration Membranes with Improved Solvent Resistance.

In this study, we report a facile preparation of an organic solvent-resistant membrane through the formation of urethane bonds between polycarbonate and polyethyleneimine groups. The modified membrane was further cross-linked with 1,4-butanediol diglycidyl ether (BDG) to enhance its solvent resistance as well as its thermal and mechanical stability. The cross-linked polycarbonate membranes exhibited improved solvent resistance with various organic solvents, giving a maximum swelling degree of 6%. It also showed better mechanical and thermal stability, as well as excellent permeance and rejection performance. This study demonstrates BDG as an attractive cross-linker for polycarbonate microfiltration membranes to transform them toward organic solvent filtration applications.

Biomechanics of Human Fetal Hearts with Critical Aortic Stenosis.

Critical aortic stenosis (AS) of the fetal heart causes a drastic change in the cardiac biomechanical environment. Consequently, a substantial proportion of such cases will lead to a single-ventricular birth outcome. However, the biomechanics of the disease is not well understood. To address this, we performed Finite Element (FE) modelling of the healthy fetal left ventricle (LV) based on patient-specific 4D ultrasound imaging, and simulated various disease features observed in clinical fetal AS to understand their biomechanical impact. These features included aortic stenosis, mitral regurgitation (MR) and LV hypertrophy, reduced contractility, and increased myocardial stiffness. AS was found to elevate LV pressures and myocardial stresses, and depending on severity, can drastically decrease stroke volume and myocardial strains. These effects are moderated by MR. AS alone did not lead to MR velocities above 3 m/s unless LV hypertrophy was included, suggesting that hypertrophy may be involved in clinical cases with high MR velocities. LV hypertrophy substantially elevated LV pressure, valve flow velocities and stroke volume, while reducing LV contractility resulted in diminished LV pressure, stroke volume and wall strains. Typical extent of hypertrophy during fetal AS in the clinic, however, led to excessive LV pressure and valve velocity in the FE model, suggesting that reduced contractility is typically associated with hypertrophy. Increased LV passive stiffness, which might represent fibroelastosis, was found to have minimal impact on LV pressures, stroke volume, and wall strain. This suggested that fibroelastosis could be a by-product of the disease progression and does not significantly impede cardiac function. Our study demonstrates that FE modelling is a valuable tool for elucidating the biomechanics of congenital heart disease and can calculate parameters which are difficult to measure, such as intraventricular pressure and myocardial stresses.

Long-Range Self-Assembly of an Electron-Deficient Hexaazatrinaphthylene with Out-of-Plane Substituents.

The unprecedented time-dependent long-range supramol-ecular assembly of electron-deficient hexaazatrinaphthylene (HATN) core based on peripheral crowding with three out-of-plane cyclic ketals is reported. The single-crystal X-ray structure of the diethyl derivative provided detailed information as to how four molecules in a repeating unit were packed in order to avoid steric crowding of the out-of-plane cyclic ketal side chain, providing locking and fastening for stabilizing the self-assembled structure. The polarizing optical microscopy (POM) and differential scanning calorimetry (DSC) did not instantaneously show any phase transition upon the cooling process. To our surprise, POM images showed a nucleation of spherulite up to 100 µm after 24 hour later. X-ray diffraction data further confirmed that these soft crystal formed a hexagonal-like crystal. The long-range self-assembly of the new material showed a slight red shift in the UV-vis absorption spectra and further substantiated by computational method.

Computational Fluid Dynamics Modeling of Hemodynamic Parameters in the Human Diseased Aorta: A Systematic Review.

BACKGROUND: The analysis of the correlation between blood flow and aortic pathology through computational fluid dynamics (CFD) shows promise in predicting disease progression, the effect of operative intervention, and guiding patient treatment. However, to date, there has not been a comprehensive systematic review of the published literature describing CFD in aortic diseases and their treatment. METHODS: This review includes 136 published articles which have investigated the application of CFD in all types of aortic disease (aneurysms, dissections, and coarctation). We took into account case studies of both, treated or untreated pathology, investigated with CFD. We also graded all studies using an author-defined Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach based on the validation method used for the CFD results. RESULTS: There are no randomized controlled trials assessing the efficacy of CFD as applied to aortic pathology, treated or untreated. Although a large number of observational studies are available, those using clinical imaging tools as independent validation of the calculated CFD results exist in far smaller numbers. Only 21% of all studies used clinical imaging as a tool to validate the CFD results and these were graded as high-quality studies. CONCLUSIONS: Contemporary evidence shows that CFD can provide additional hemodynamic parameters such as wall shear stress, vorticity, disturbed laminar flow, and recirculation regions in untreated and treated aortic disease. These have the potential to predict the progression of aortic disease, the effect of operative intervention, and ultimately help guide the choice and timing of treatment to the benefit of patients and clinicians alike.

Ventricular vortex loss analysis due to various tricuspid valve repair techniques: an ex vivo study.

The deteriorating nature of severe functional tricuspid regurgitation (FTR) has led to the heightened interest in this pathology. However, therapies are heterogeneous and an ideal technique is uncertain. The hemodynamic impact on the cardiac chamber following therapeutic repairs has not been well studied, while its analysis could be used to predict the treatment success. In this study, the hemodynamics of the right ventricle (RV) after 1) clover edge-to-edge tricuspid repair, and 2) double orifice tricuspid repair was evaluated in three right heart models using an ex vivo pulsatile platform emulating severe FTR with the aid of stereoscopic particle image velocimetry. Although all repairs substantially reduced tricuspid regurgitant area, they resulted in a more than 50% reduction in diastolic tricuspid valve (TV) opening area. Splitting the TV orifice into multiple smaller orifices by both repairs eliminated the ring-shaped vortical structure inside the RV observed in FTR cases. Postrepair RV domain was mostly occupied with irregular vortical features and isolated vortex residuals. Moreover, vortical features varied among repair samples, indicating enhanced sensitivity of RV flow to postrepair TV morphology. Compared with clover repair, double orifice subjected the RV to enhanced swirling motions and exposed more regions to vortical motions, potentially indicating better rinsing and lower risk of mural thrombus formation. Double orifice repair increased the levels of RV mean kinetic energy and viscous energy loss than those observed in clover repair, although the impact of these on the cardiac efficiency remains unclear. These preliminary insights could be used to improve future treatment design and planning.NEW & NOTEWORTHY While clover and double orifice tricuspid repairs markedly improved leaflet coaptation, they substantially reduced diastolic tricuspid opening area. Postrepair right ventricle (RV) exhibited specific hemodynamic traits, including the loss of ring-shaped vortical structure and the enhanced sensitivity of RV flow to postrepair tricuspid valve morphology. Compared with clover technique, double orifice repair led to higher swirling motions in the RV domain, which could indicate lower risk of mural thrombus formation.

Superstructure manipulation and electronic measurement of monolayers comprising discotic liquid crystals with intrinsic dipole moment using STM/STS.

In this work, we studied the discotic liquid crystals (DLCs) of dibenzo[a,c]phenazine at the liquid-solid interface using scanning tunnelling microscopy/spectroscopy, by which we show how to tailor the DLC assemblies and in turn their electron-transfer efficiency. This study presents an alternative method for phase control and electronic measurements for DLCs, especially at the microscopic level.