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Determining the structure and mechanisms of all individual functional modules of cells at high molecular detail has often been seen as equal to understanding how cells work. Recent technical advances have led to a flush of high-resolution structures of various macromolecular machines, but despite this wealth of detailed information, our understanding of cellular function remains incomplete. Here, we discuss present-day limitations of structural biology and highlight novel technologies that may enable us to analyze molecular functions directly inside cells. We predict that the progression toward structural cell biology will involve a shift toward conceptualizing a 4D virtual reality of cells using digital twins. These will capture cellular segments in a highly enriched molecular detail, include dynamic changes, and facilitate simulations of molecular processes, leading to novel and experimentally testable predictions. Transferring biological questions into algorithms that learn from the existing wealth of data and explore novel solutions may ultimately unveil how cells work.
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Biología , Biología Computacional , Sustancias Macromoleculares/químicaRESUMEN
Networks allow us to describe a wide range of interaction phenomena that occur in complex systems arising in such diverse fields of knowledge as neuroscience, engineering, ecology, finance, and social sciences. Until very recently, the primary focus of network models and tools has been on describing the pairwise relationships between system entities. However, increasingly more studies indicate that polyadic or higher-order group relationships among multiple network entities may be the key toward better understanding of the intrinsic mechanisms behind the functionality of complex systems. Such group interactions can be, in turn, described in a holistic manner by simplicial complexes of graphs. Inspired by these recently emerging results on the utility of the simplicial geometry of complex networks for contagion propagation and armed with a large-scale synthetic social contact network (also known as a digital twin) of the population in the U.S. state of Virginia, in this paper, we aim to glean insights into the role of higher-order social interactions and the associated varying social group determinants on COVID-19 propagation and mitigation measures.
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COVID-19 , Epidemias , Humanos , COVID-19/epidemiología , VirginiaRESUMEN
Here, we combine international air travel passenger data with a standard epidemiological model of the initial 3 mo of the COVID-19 pandemic (January through March 2020; toward the end of which the entire world locked down). Using the information available during this initial phase of the pandemic, our model accurately describes the main features of the actual global development of the pandemic demonstrated by the high degree of coherence between the model and global data. The validated model allows for an exploration of alternative policy efficacies (reducing air travel and/or introducing different degrees of compulsory immigration quarantine upon arrival to a country) in delaying the global spread of SARS-CoV-2 and thus is suggestive of similar efficacy in anticipating the spread of future global disease outbreaks. We show that a lesson from the recent pandemic is that reducing air travel globally is more effective in reducing the global spread than adopting immigration quarantine. Reducing air travel out of a source country has the most important effect regarding the spreading of the disease to the rest of the world. Based upon our results, we propose a digital twin as a further developed tool to inform future pandemic decision-making to inform measures intended to control the spread of disease agents of potential future pandemics. We discuss the design criteria for such a digital twin model as well as the feasibility of obtaining access to the necessary online data on international air travel.
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Viaje en Avión , COVID-19 , Humanos , Pandemias/prevención & control , COVID-19/epidemiología , COVID-19/prevención & control , SARS-CoV-2 , Brotes de EnfermedadesRESUMEN
The power grid is going through significant changes with the introduction of renewable energy sources and the incorporation of smart grid technologies. These rapid advancements necessitate new models and analyses to keep up with the various emergent phenomena they induce. A major prerequisite of such work is the acquisition of well-constructed and accurate network datasets for the power grid infrastructure. In this paper, we propose a robust, scalable framework to synthesize power distribution networks that resemble their physical counterparts for a given region. We use openly available information about interdependent road and building infrastructures to construct the networks. In contrast to prior work based on network statistics, we incorporate engineering and economic constraints to create the networks. Additionally, we provide a framework to create ensembles of power distribution networks to generate multiple possible instances of the network for a given region. The comprehensive dataset consists of nodes with attributes, such as geocoordinates; type of node (residence, transformer, or substation); and edges with attributes, such as geometry, type of line (feeder lines, primary or secondary), and line parameters. For validation, we provide detailed comparisons of the generated networks with actual distribution networks. The generated datasets represent realistic test systems (as compared with standard test cases published by Institute of Electrical and Electronics Engineers (IEEE)) that can be used by network scientists to analyze complex events in power grids and to perform detailed sensitivity and statistical analyses over ensembles of networks.
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Suministros de Energía EléctricaRESUMEN
Human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) offer potential as an in vitro model for studying drug cardiotoxicity and patient-specific cardiovascular disease. The inherent electrophysiological heterogeneity of these cells limits the depth of insights that can be drawn from well-designed experiments. In this review, we provide our perspective on some sources and the consequences of iPSC-CM heterogeneity. We demonstrate the extent of heterogeneity in the literature and explain how such heterogeneity is exacerbated by patch-clamp experimental artifacts in the manual and automated set-up. Finally, we discuss how this heterogeneity, caused by both intrinsic and extrinsic factors, limits our ability to build digital twins of patient-derived cardiomyocytes.
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All-solid-state lithium batteries (ASSLBs) are considered promising alternatives to current lithium-ion batteries that employ liquid electrolytes due to their high energy density and enhanced safety. Among various types of solid electrolytes, sulfide-based electrolytes are being actively studied, because they exhibit high ionic conductivity and high ductility, which enable good interfacial contacts in solid electrolytes without sintering at high temperatures. To improve the energy density of the sulfide-based ASSLBs, it is essential to increase the loading of active material in the composite cathode. In this study, the Ni-rich LiNix Coy Mn1-x-y O2 (NCM) materials are explored with different Ni content, particle size, and crystalline form to probe suitable cathode active materials for high-performance ASSLBs with high energy density. The results reveal that single-crystalline LiNi0.82 Co0.10 Mn0.08 O2 material with a small particle size exhibits the best cycling performance in the ASSLB assembled with a high mass loaded cathode (active mass loading: 26 mg cm-2 , areal capacity: 5.0 mAh cm-2 ) in terms of discharge capacity, capacity retention, and rate capability.
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The fifth modeling workshop (5MW) was held in June 2023 at Favrholm, Denmark and sponsored by Recovery of Biological Products Conference Series. The goal of the workshop was to assemble modeling practitioners to review and discuss the current state, progress since the last fourth mini modeling workshop (4MMW), gaps and opportunities for development, deployment and maintenance of models in bioprocess applications. Areas of focus were four categories: biophysics and molecular modeling, mechanistic modeling, computational fluid dynamics (CFD) and plant modeling. Highlights of the workshop included significant advancements in biophysical/molecular modeling to novel protein constructs, mechanistic models for filtration and initial forays into modeling of multiphase systems using CFD for a bioreactor and mapped strategically to cell line selection/facility fit. A significant impediment to more fully quantitative and calibrated models for biophysics is the lack of large, anonymized datasets. A potential solution would be the use of specific descriptors in a database that would allow for detailed analyzes without sharing proprietary information. Another gap identified was the lack of a consistent framework for use of models that are included or support a regulatory filing beyond the high-level guidance in ICH Q8-Q11. One perspective is that modeling can be viewed as a component or precursor of machine learning (ML) and artificial intelligence (AI). Another outcome was alignment on a key definition for "mechanistic modeling." Feedback from participants was that there was progression in all of the fields of modeling within scope of the conference. Some areas (e.g., biophysics and molecular modeling) have opportunities for significant research investment to realize full impact. However, the need for ongoing research and development for all model types does not preclude the application to support process development, manufacturing and use in regulatory filings. Analogous to ML and AI, given the current state of the four modeling types, a prospective investment in educating inter-disciplinary subject matter experts (e.g., data science, chromatography) is essential to advancing the modeling community.
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Simulación por Computador , Modelos Biológicos , Industria FarmacéuticaRESUMEN
Digital twin (DT) is a virtual and digital representation of physical objects or processes. In this paper, this concept is applied to dynamic control of the collection window in the ion exchange chromatography (IEC) toward sample variations. A possible structure of a feedforward model-based control DT system was proposed. Initially, a precise IEC mechanistic model was established through experiments, model fitting, and validation. The average root mean square error (RMSE) of fitting and validation was 8.1% and 7.4%, respectively. Then a model-based gradient optimization was performed, resulting in a 70.0% yield with a remarkable 11.2% increase. Subsequently, the DT was established by systematically integrating the model, chromatography system, online high-performance liquid chromatography, and a server computer. The DT was validated under varying load conditions. The results demonstrated that the DT could offer an accurate control with acidic variants proportion and yield difference of less than 2% compared to the offline analysis. The embedding mechanistic model also showed a positive predictive performance with an average RMSE of 11.7% during the DT test under >10% sample variation. Practical scenario tests indicated that tightening the control target could further enhance the DT robustness, achieving over 98% success rate with an average yield of 72.7%. The results demonstrated that the constructed DT could accurately mimic real-world situations and perform an automated and flexible pooling in IEC. Additionally, a detailed methodology for applying DT was summarized.
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Anticuerpos Monoclonales , Cromatografía Líquida de Alta Presión/métodos , Anticuerpos Monoclonales/química , Cromatografía por Intercambio Iónico/métodosRESUMEN
Reinforcement learning (RL), a subset of machine learning (ML), could optimize and control biomanufacturing processes, such as improved production of therapeutic cells. Here, the process of CAR T-cell activation by antigen-presenting beads and their subsequent expansion is formulated in silico. The simulation is used as an environment to train RL-agents to dynamically control the number of beads in culture to maximize the population of robust effector cells at the end of the culture. We make periodic decisions of incremental bead addition or complete removal. The simulation is designed to operate in OpenAI Gym, enabling testing of different environments, cell types, RL-agent algorithms, and state inputs to the RL-agent. RL-agent training is demonstrated with three different algorithms (PPO, A2C, and DQN), each sampling three different state input types (tabular, image, mixed); PPO-tabular performs best for this simulation environment. Using this approach, training of the RL-agent on different cell types is demonstrated, resulting in unique control strategies for each type. Sensitivity to input-noise (sensor performance), number of control step interventions, and advantages of pre-trained RL-agents are also evaluated. Therefore, we present an RL framework to maximize the population of robust effector cells in CAR T-cell therapy production.
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Aprendizaje Automático , Linfocitos T , Linfocitos T/inmunología , Humanos , Simulación por Computador , Activación de Linfocitos , Receptores Quiméricos de Antígenos/inmunología , Inmunoterapia Adoptiva/métodos , Técnicas de Cultivo de Célula/métodosRESUMEN
BACKGROUND AND AIMS: The effective refractory period (ERP) is one of the main electrophysiological properties governing arrhythmia, yet ERP personalisation is rarely performed when creating patient-specific computer models of the atria to inform clinical decision-making. This study evaluates the impact of integrating clinical ERP measurements into personalised in silico models on arrhythmia vulnerability. METHODS: Clinical ERP measurements were obtained in seven patients from multiple locations in the atria. Atrial geometries from the electroanatomical mapping system were used to generate personalised anatomical atrial models. The Courtemanche cellular model was adjusted to reproduce patientspecific ERP. Four modelling approaches were compared: homogeneous (A), heterogeneous (B), regional (C), and continuous (D) ERP distributions. Non-personalised approaches (A, B) were based on literature data, while personalised approaches (C, D) were based on patient measurements. Modelling effects were assessed on arrhythmia vulnerability and tachycardia cycle length, with sensitivity analysis on ERP measurement uncertainty. RESULTS: Mean vulnerability was 3.4±4.0%, 7.7±3.4%, 9.0±5.1%, 7.0±3.6% for scenarios A to D, respectively. Mean tachycardia cycle length was 167.1±12.6 ms, 158.4±27.5 ms, 265.2±39.9 ms, and 285.9±77.3 ms for scenarios A to D, respectively. Incorporating perturbations to the measured ERP in the range of 2, 5, 10, 20, and 50ms changed the vulnerability of the model to 5.8±2.7%, 6.1±3.5%, 6.9±3.7%, 5.2±3.5%, 9.7±10.0% respectively. CONCLUSION: Increased ERP dispersion had a greater effect on reentry dynamics than on vulnerability. Inducibility was higher in personalised scenarios compared to scenarios with uniformly reduced ERP; however, this effect was reversed when incorporating fibrosis informed by low voltage areas.ERP measurement uncertainty up to 20 ms slightly influenced vulnerability. Electrophysiological personalisation of atrial in silico models appears essential and requires confirmation in larger cohorts.
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BACKGROUND AND AIMS: Right bundle branch block (RBBB) and resulting right ventricular (RV) electromechanical discoordination are thought to play a role in the disease process of subpulmonary RV dysfunction that frequently occur post-repair tetralogy of Fallot (ToF). We sought to describe this disease entity, the role of pulmonary re-valvulation, and the potential added value of RV cardiac resynchronization therapy (RV-CRT). METHODS: Two patients with repaired ToF, complete RBBB, pulmonary regurgitation, and significantly decreased RV function underwent echocardiography, cardiac magnetic resonance, and an invasive study to evaluate the potential for RV-CRT as part of the management strategy. The data were used to personalize the CircAdapt model of the human heart and circulation. Resulting Digital Twins were analysed to quantify the relative effects of RV pressure and volume overload and to predict the effect of RV-CRT. RESULTS: Echocardiography showed components of a classic RV dyssynchrony pattern which could be reversed by RV-CRT during invasive study and resulted in acute improvement in RV systolic function. The Digital Twins confirmed a contribution of electromechanical RV dyssynchrony to RV dysfunction and suggested improvement of RV contraction efficiency after RV-CRT. The one patient who underwent successful permanent RV-CRT as part of the pulmonary re-valvulation procedure carried improvements that were in line with the predictions based on his Digital Twin. CONCLUSION: An integrative diagnostic approach to RV dysfunction, including the construction of Digital Twins may help to identify candidates for RV-CRT as part of the lifetime management of ToF and similar congenital heart lesions.
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Terapia de Resincronización Cardíaca , Tetralogía de Fallot , Disfunción Ventricular Derecha , Humanos , Tetralogía de Fallot/diagnóstico por imagen , Tetralogía de Fallot/cirugía , Ventrículos Cardíacos , Ecocardiografía , Terapia de Resincronización Cardíaca/efectos adversos , Bloqueo de Rama/diagnóstico por imagen , Bloqueo de Rama/etiología , Bloqueo de Rama/terapia , Disfunción Ventricular Derecha/diagnóstico por imagen , Disfunción Ventricular Derecha/etiología , Disfunción Ventricular Derecha/terapia , Simulación por ComputadorRESUMEN
The Spherical Tokamak for Energy Production (STEP) programme is an ambitious but challenging endeavour to design and deliver a prototype fusion power plant. It is a rapid, fast-moving programme, designing a first of a kind device in a Volatile, Uncertain, Complex and Ambiguous (VUCA) environment, and digital tools play a pivotal role in managing and navigating this space. Digital helps manage the complexity and sheer volume of information. Advanced modelling and simulation techniques provide a platform for designers to explore various scenarios and iteratively refine designs, providing insights into the intricate interplay of requirements, constraints and design factors across physics, technology and engineering domains and aiding informed decision-making amidst uncertainties. It also provides a means of building confidence in the new scientific, technological and engineering solutions, given that a full-scale-integrated precursor test is not feasible, almost by definition. The digital strategy for STEP is built around a vision of a digital twin of the whole plant. This will evolve from the current digital shadow formed by system architecting codes and complex workflows and will be underpinned by developing capabilities in plasma, materials and engineering simulation, data management, advanced control, industrial cybersecurity, regulation, digital technologies and related digital disciplines. These capabilities will help address the key challenges of managing the complexity and quantity of information, improving the reliability and robustness of the current digital shadow and developing an understanding of its validity and performance.This article is part of the theme issue 'Delivering Fusion Energy - The Spherical Tokamak for Energy Production (STEP)'.
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BACKGROUND: Integration of a patient's non-invasive imaging data in a digital twin (DT) of the heart can provide valuable insight into the myocardial disease substrates underlying left ventricular (LV) mechanical discoordination. However, when generating a DT, model parameters should be identifiable to obtain robust parameter estimations. In this study, we used the CircAdapt model of the human heart and circulation to find a subset of parameters which were identifiable from LV cavity volume and regional strain measurements of patients with different substrates of left bundle branch block (LBBB) and myocardial infarction (MI). To this end, we included seven patients with heart failure with reduced ejection fraction (HFrEF) and LBBB (study ID: 2018-0863, registration date: 2019-10-07), of which four were non-ischemic (LBBB-only) and three had previous MI (LBBB-MI), and six narrow QRS patients with MI (MI-only) (study ID: NL45241.041.13, registration date: 2013-11-12). Morris screening method (MSM) was applied first to find parameters which were important for LV volume, regional strain, and strain rate indices. Second, this parameter subset was iteratively reduced based on parameter identifiability and reproducibility. Parameter identifiability was based on the diaphony calculated from quasi-Monte Carlo simulations and reproducibility was based on the intraclass correlation coefficient ( ICC ) obtained from repeated parameter estimation using dynamic multi-swarm particle swarm optimization. Goodness-of-fit was defined as the mean squared error ( χ 2 ) of LV myocardial strain, strain rate, and cavity volume. RESULTS: A subset of 270 parameters remained after MSM which produced high-quality DTs of all patients ( χ 2 < 1.6), but minimum parameter reproducibility was poor ( ICC min = 0.01). Iterative reduction yielded a reproducible ( ICC min = 0.83) subset of 75 parameters, including cardiac output, global LV activation duration, regional mechanical activation delay, and regional LV myocardial constitutive properties. This reduced subset produced patient-resembling DTs ( χ 2 < 2.2), while septal-to-lateral wall workload imbalance was higher for the LBBB-only DTs than for the MI-only DTs (p < 0.05). CONCLUSIONS: By applying sensitivity and identifiability analysis, we successfully determined a parameter subset of the CircAdapt model which can be used to generate imaging-based DTs of patients with LV mechanical discoordination. Parameters were reproducibly estimated using particle swarm optimization, and derived LV myocardial work distribution was representative for the patient's underlying disease substrate. This DT technology enables patient-specific substrate characterization and can potentially be used to support clinical decision making.
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Ventrículos Cardíacos , Procesamiento de Imagen Asistido por Computador , Humanos , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/fisiopatología , Procesamiento de Imagen Asistido por Computador/métodos , Bloqueo de Rama/diagnóstico por imagen , Bloqueo de Rama/fisiopatología , Fenómenos Biomecánicos , Infarto del Miocardio/diagnóstico por imagen , Infarto del Miocardio/fisiopatología , Fenómenos Mecánicos , Masculino , Femenino , Persona de Mediana Edad , Modelos CardiovascularesRESUMEN
Digital twins are virtual replicas of their physical counterparts, and can assist in delivering personalized surgical care. This PRISMA guideline-based systematic review evaluates current literature addressing the effectiveness and role of digital twins in many stages of neurosurgical management. The aim of this review is to provide a high-quality analysis of relevant, randomized controlled trials and observational studies addressing the neurosurgical applicability of a variety of digital twin technologies. Using pre-specified criteria, we evaluated 25 randomized controlled trials and observational studies on the applications of digital twins, including navigation, robotics, and image-guided neurosurgeries. All 25 studies compared these technologies against usual surgical approaches. Risk of bias analyses using the Cochrane risk of bias tool for randomized trials (Rob 2) found "low" risk of bias in the majority of studies (23/25). Overall, this systematic review shows that digital twin applications have the potential to be more effective than conventional neurosurgical approaches when applied to brain and spinal surgery. Moreover, the application of these novel technologies may also lead to fewer post-operative complications.
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Neurocirugia , Humanos , Procedimientos Neuroquirúrgicos , Encéfalo , Complicaciones Posoperatorias , Estudios Observacionales como AsuntoRESUMEN
This paper presents a modular software design for the construction of computational modeling technology that will help implement precision medicine. In analogy to a common industrial strategy used for preventive maintenance of engineered products, medical digital twins are computational models of disease processes calibrated to individual patients using multiple heterogeneous data streams. They have the potential to help improve diagnosis, prognosis, and personalized treatment for a wide range of medical conditions. Their large-scale development relies on both mechanistic and data-driven techniques and requires the integration and ongoing update of multiple component models developed across many different laboratories. Distributed model building and integration requires an open-source modular software platform for the integration and simulation of models that is scalable and supports a decentralized, community-based model building process. This paper presents such a platform, including a case study in an animal model of a respiratory fungal infection.
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Aspergilosis/tratamiento farmacológico , Biología Computacional/métodos , Modelación Específica para el Paciente , Medicina de Precisión/métodos , Programas Informáticos , Algoritmos , Animales , Antifúngicos/farmacología , Aspergilosis/microbiología , Aspergilosis/patología , Aspergillus fumigatus/crecimiento & desarrollo , Aspergillus fumigatus/patogenicidad , Humanos , Esporas Fúngicas/crecimiento & desarrollo , Esporas Fúngicas/patogenicidadRESUMEN
Digital twins have emerged as a groundbreaking concept in personalized medicine, offering immense potential to transform health care delivery and improve patient outcomes. It is important to highlight the impact of digital twins on personalized medicine across the understanding of patient health, risk assessment, clinical trials and drug development, and patient monitoring. By mirroring individual health profiles, digital twins offer unparalleled insights into patient-specific conditions, enabling more accurate risk assessments and tailored interventions. However, their application extends beyond clinical benefits, prompting significant ethical debates over data privacy, consent, and potential biases in health care. The rapid evolution of this technology necessitates a careful balancing act between innovation and ethical responsibility. As the field of personalized medicine continues to evolve, digital twins hold tremendous promise in transforming health care delivery and revolutionizing patient care. While challenges exist, the continued development and integration of digital twins hold the potential to revolutionize personalized medicine, ushering in an era of tailored treatments and improved patient well-being. Digital twins can assist in recognizing trends and indicators that might signal the presence of diseases or forecast the likelihood of developing specific medical conditions, along with the progression of such diseases. Nevertheless, the use of human digital twins gives rise to ethical dilemmas related to informed consent, data ownership, and the potential for discrimination based on health profiles. There is a critical need for robust guidelines and regulations to navigate these challenges, ensuring that the pursuit of advanced health care solutions does not compromise patient rights and well-being. This viewpoint aims to ignite a comprehensive dialogue on the responsible integration of digital twins in medicine, advocating for a future where technology serves as a cornerstone for personalized, ethical, and effective patient care.
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Medicina de Precisión , Medicina de Precisión/métodos , Medicina de Precisión/tendencias , Humanos , Atención a la Salud/tendencias , Atención a la Salud/ética , Atención a la Salud/métodos , Consentimiento Informado/ética , Confidencialidad/éticaRESUMEN
Digital twins have become a popular and widely used tool for assessing risk and resilience, particularly as they have increased in the fidelity and accuracy of their representation of real-world systems. Although digital twins provide the ability to experiment on and assess risks to and from a system without damaging the real-world system, they pose potentially significant security risks. For example, if a digital twin of a power system has sufficient accuracy to allow loss of electrical power service due to a natural hazard to be estimated at the address level with a high degree of accuracy, what prevents someone wishing to lead to disruption at this same building from using the model to solve the inverse problem to determine which parts of the power system should be attacked to maximize the likelihood of loss of service to the target facility? This perspective article discusses the benefits and risks of digital twins and argues that more attention needs to be paid to the risks posed by digital twins.
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Emerging from the convergence of digital twin technology and the metaverse, consumer health (MCH) is witnessing a transformative shift. The amalgamation of bioinformatics with healthcare Big Data has ushered in a new era of disease prediction models that harness comprehensive medical data, enabling the anticipation of illnesses even before the onset of symptoms. In this model, deep neural networks stand out because they improve accuracy remarkably by increasing network depth and making weight changes using gradient descent. Nonetheless, traditional methods face their own set of challenges, including the issues of gradient instability and slow training. In this case, the Broad Learning System (BLS) stands out as a good alternative. It gets around the problems with gradient descent and lets you quickly rebuild a model through incremental learning. One problem with BLS is that it has trouble extracting complex features from complex medical data. This makes it less useful in a wide range of healthcare situations. In response to these challenges, we introduce DAE-BLS, a novel hybrid model that marries Denoising AutoEncoder (DAE) noise reduction with the efficiency of BLS. This hybrid approach excels in robust feature extraction, particularly within the intricate and multifaceted world of medical data. Validation using diverse datasets yields impressive results, with accuracies reaching as high as 98.50%. DAE-BLS's ability to rapidly adapt through incremental learning holds great promise for accurate and agile disease prediction, especially within the complex and dynamic healthcare scenarios of today.
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Macrodatos , Tecnología , Humanos , Biología Computacional , Instituciones de Salud , Redes Neurales de la ComputaciónRESUMEN
In recognition of the importance and timeliness of computational models for accelerating progress in neurorehabilitation, the U.S. National Science Foundation (NSF) and the National Institutes of Health (NIH) sponsored a conference in March 2023 at the University of Southern California that drew global participation from engineers, scientists, clinicians, and trainees. This commentary highlights promising applications of computational models to understand neurorehabilitation ("Using computational models to understand complex mechanisms in neurorehabilitation" section), improve rehabilitation care in the context of digital twin frameworks ("Using computational models to improve delivery and implementation of rehabilitation care" section), and empower future interdisciplinary workforces to deliver higher-quality clinical care using computational models ("Using computational models in neurorehabilitation requires an interdisciplinary workforce" section). The authors describe near-term gaps and opportunities, all of which encourage interdisciplinary team science. Four major opportunities were identified including (1) deciphering the relationship between engineering figures of merit-a term commonly used by engineers to objectively quantify the performance of a device, system, method, or material relative to existing state of the art-and clinical outcome measures, (2) validating computational models from engineering and patient perspectives, (3) creating and curating datasets that are made publicly accessible, and (4) developing new transdisciplinary frameworks, theories, and models that incorporate the complexities of the nervous and musculoskeletal systems. This commentary summarizes U.S. funding opportunities by two Federal agencies that support computational research in neurorehabilitation. The NSF has funding programs that support high-risk/high-reward research proposals on computational methods in neurorehabilitation informed by theory- and data-driven approaches. The NIH supports the development of new interventions and therapies for a wide range of nervous system injuries and impairments informed by the field of computational modeling. The conference materials can be found at https://dare2023.usc.edu/ .
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National Institutes of Health (U.S.) , Rehabilitación Neurológica , Estados Unidos , HumanosRESUMEN
In 2023, the National Science Foundation (NSF) and the National Institute of Health (NIH) brought together engineers, scientists, and clinicians by sponsoring a conference on computational modelling in neurorehabiilitation. To facilitate multidisciplinary collaborations and improve patient care, in this perspective piece we identify where and how computational modelling can support neurorehabilitation. To address the where, we developed a patient-in-the-loop framework that uses multiple and/or continual measurements to update diagnostic and treatment model parameters, treatment type, and treatment prescription, with the goal of maximizing clinically-relevant functional outcomes. This patient-in-the-loop framework has several key features: (i) it includes diagnostic and treatment models, (ii) it is clinically-grounded with the International Classification of Functioning, Disability and Health (ICF) and patient involvement, (iii) it uses multiple or continual data measurements over time, and (iv) it is applicable to a range of neurological and neurodevelopmental conditions. To address the how, we identify state-of-the-art and highlight promising avenues of future research across the realms of sensorimotor adaptation, neuroplasticity, musculoskeletal, and sensory & pain computational modelling. We also discuss both the importance of and how to perform model validation, as well as challenges to overcome when implementing computational models within a clinical setting. The patient-in-the-loop approach offers a unifying framework to guide multidisciplinary collaboration between computational and clinical stakeholders in the field of neurorehabilitation.