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Today, the area of point-of-care diagnostics is synonymous with paper microfluidics where cheap, disposable, and on-the-spot detection toolkits are being developed for a variety of chemical tests. In this work, we present a novel application of microfluidic paper-based analytical devices (μPADs) to study the behavior of a small model nematode, Caenorhabditis elegans. We describe schemes of μPAD fabrication on paper and plastic substrates where membranes are created in agarose and Pluronic gel. Methods are demonstrated for loading, visualizing, and transferring single and multiple nematodes. Using an anthelmintic drug, levamisole, we show that chemical testing on C. elegans is easily performed because of the open device structure. A custom program is written to automatically recognize individual worms on the μPADs and extract locomotion parameters in real-time. The combination of μPADs and the nematode tracking program provides a relatively low-cost, simple-to-fabricate imaging and screening assay (compared to standard agarose plates or polymeric microfluidic devices) for non-microfluidic, nematode laboratories.

Meta-biomaterials, engineered materials with distinctive combinations of mechanical, physical, and biological properties stemming from their micro-architecture, have emerged as a promising domain within biomedical engineering. Correspondingly, meta-implants, which serve as the device counterparts of meta-biomaterials, offer exceptional functionalities, holding great potential for addressing complex skeletal diseases. This paper presents a comprehensive overview of the various types of meta-implants, including hybrid, shape-morphing, metallic clay, and deployable meta-implants, highlighting their unprecedented properties and recent achievement in the field. This paper also delves into the potential future developments of meta-implants, addressing the exploration of multi-functionalities in meta-biomaterials and their applications in diverse biomedical fields. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes mellitus (T2DM) is the most common type of diabetes, accounting for around 90% of all diabetes. Studies have found that dietary habits and biochemical metabolic changes are closely related to T2DM disease surveillance, but early surveillance tools are not specific and have lower accuracy. This paper aimed to provide a reliable artificial intelligence model with high accuracy for the clinical diagnosis of T2DM. Methods: A cross-sectional dataset comprising 8981 individuals from the First Affiliated Hospital of Guangxi Medical University was analyzed by a model fusion framework. The model includes four machine learning (ML) models, which used the stacking method. The ability to leverage the strengths of different algorithms to capture complex patterns in the data can effectively combine questionnaire data and blood test data to predict diabetes. Results: The experimental results show that the stacking model achieves significant prediction results in diabetes detection. Compared with the single machine learning algorithm, the stacking model has improved in the metrics of accuracy, recall, and F1-score. The test set accuracy is 0.90, and the precision, recall, F1-score, area under the curve, and average precision (AP) are 0.91, 0.90, 0.90, 0.90, and 0.85, respectively. Additionally, this study showed that HbA1c (P < 0.001,OR = 2.203), fasting blood glucose (FBG) (P < 0.001,OR = 1.586), Ph2BG (P < 0.001,OR = 1.190), age (P < 0.001,OR = 1.018), Han nationality (P < 0.001,OR = 1.484), and carbonate beverages (P = 0.001,OR = 1.347) were important predictors of T2DM. Conclusion: This study demonstrates that stacking models show great potential in diabetes detection, and by integrating multiple machine learning algorithms, stacking models can significantly improve the accuracy and stability of diabetes prediction and provide strong support for disease prevention, early diagnosis, and individualized treatment. [ABSTRACT FROM AUTHOR]

The demand for ambulatory blood pressure monitoring (ABPM) is increasing due to the global rise in cardiovascular disease patients. However, conventional ABPM methods are discontinuous and can disrupt daily activities and sleep patterns. Photoplethysmography (PPG) is gaining attention from researchers due to its simplicity, portability, affordability, and ease of signal acquisition. This paper critically examines the advancements achieved in the technology of PPG-guided noninvasive blood pressure (BP) monitoring and explores future opportunities. We have performed a literature search using the Web of Science and PubMed search engines, from January 2018 to October 2023, for PPG signal quality assessment (SQA), cuffless BP estimation using single PPG, and associations between circadian rhythm and BP. Based on this foundation, we first examine the impact of PPG signal quality on blood pressure estimation results while focusing on methods for assessing PPG signal quality. Subsequently, the methods documented for estimating cuff-free BP from PPG signals are summarized. Furthermore, the study examines how individual differences affect the accuracy of BP estimation, incorporating the factors that influence arterial blood pressure (ABP) and elucidating the impact of circadian rhythm on blood pressure. Finally, there will be a summary of the study's findings and suggestions for future research directions. [ABSTRACT FROM AUTHOR]

Novel hearable technology is securely and comfortably positioned within the ear canal minimizing inaccuracies caused by accessory movements during activities. Despite extensive research on hearable technologies within the outer ear, there is a lack of research in the field of vascular imaging and quantitative analysis in the outer ear in vivo, which is one of the crucial factors to select the appropriate sensor position. Therefore, in this paper, we introduced optical coherence tomography angiography (OCTA)-based qualitative and quantitative analyses to visualize the inner vasculature of the outer ear to acquire vascular maps for microvascular assessments in vivo. By generating maximum amplitude projection images from three-dimensional blood vascular volume, we identified variations of blood vessel signal caused by the different biological characteristics and curvature of the ear among individuals. The performance of micro-vascular mapping using the proposed method was validated through the comparison and analysis of individual vascular parameters using extracted 20 vascular-related variables. In addition, we extracted pulsatile blood flow signals, demonstrating its potential to provide photoplethysmographic signals and ear blood maps simultaneously. Therefore, our proposed OCTA-based method for ear vascular mapping successfully provides quantitative information about ear vasculature, which is potentially used for determining the position of system-on-chip sensors for health monitoring in hearable devices. [ABSTRACT FROM AUTHOR]

Cancer, with high morbidity and high mortality, is one of the major burdens threatening human health globally. Intervention procedures via percutaneous puncture have been widely used by physicians due to its minimally invasive surgical approach. However, traditional manual puncture intervention depends on personal experience and faces challenges in terms of precisely puncture, learning-curve, safety and efficacy. The development of puncture interventional surgery robotic (PISR) systems could alleviate the aforementioned problems to a certain extent. This paper attempts to review the current status and prospective of PISR systems for thoracic and abdominal application. In this review, the key technologies related to the robotics, including spatial registration, positioning navigation, puncture guidance feedback, respiratory motion compensation, and motion control, are discussed in detail. [ABSTRACT FROM AUTHOR]

Meta-biomaterials, engineered materials with distinctive combinations of mechanical, physical, and biological properties stemming from their micro-architecture, have emerged as a promising domain within biomedical engineering. Correspondingly, meta-implants, which serve as the device counterparts of meta-biomaterials, offer exceptional functionalities, holding great potential for addressing complex skeletal diseases. This paper presents a comprehensive overview of the various types of meta-implants, including hybrid, shape-morphing, metallic clay, and deployable meta-implants, highlighting their unprecedented properties and recent achievement in the field. This paper also delves into the potential future developments of meta-implants, addressing the exploration of multi-functionalities in meta-biomaterials and their applications in diverse biomedical fields.

The scientific community has shown increasing interest in laser scribing for the direct fabrication of conductive graphene-based tracks on different substrates. This can enable novel routes for the noninvasive analysis of biofluids (such as sweat or other noninvasive matrices), whose results can provide the rapid evaluation of a person's health status. Here, we present a wearable sensing platform based on laser induced graphene (LIG) porous electrodes scribed on a flexible polyimide sheet, which samples sweat through a paper sampler. The device is fully laser manufactured and features a two layer design with LIG-based vertical interconnect accesses. A detailed characterization of the LIG electrodes including pore size, surface groups, surface area in comparison to electroactive surface area, and the reduction behavior of different LIG types was performed. The bare LIG electrodes can detect the electrochemical oxidation of both uric acid and tyrosine. Further modification of the surface of the LIG working electrode with an indoaniline derivative [4-((4-aminophenyl)imino)-2,6-dimethoxycyclohexa-2,5-dien-1-one] enables the voltammetric measurement of pH with an almost ideal sensitivity and without interference from other analytes. Finally, electrochemical impedance spectroscopy was used to measure the concentrations of ions through the analysis of the sweat impedance. The device was successfully tested in a real case scenario, worn on the skin during a sports session. In vitro tests proved the non-cytotoxic effect of the device on the A549 cell line. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes mellitus (T2DM) is the most common type of diabetes, accounting for around 90% of all diabetes. Studies have found that dietary habits and biochemical metabolic changes are closely related to T2DM disease surveillance, but early surveillance tools are not specific and have lower accuracy. This paper aimed to provide a reliable artificial intelligence model with high accuracy for the clinical diagnosis of T2DM. Methods: A cross-sectional dataset comprising 8981 individuals from the First Affiliated Hospital of Guangxi Medical University was analyzed by a model fusion framework. The model includes four machine learning (ML) models, which used the stacking method. The ability to leverage the strengths of different algorithms to capture complex patterns in the data can effectively combine questionnaire data and blood test data to predict diabetes. Results: The experimental results show that the stacking model achieves significant prediction results in diabetes detection. Compared with the single machine learning algorithm, the stacking model has improved in the metrics of accuracy, recall, and F1-score. The test set accuracy is 0.90, and the precision, recall, F1-score, area under the curve, and average precision (AP) are 0.91, 0.90, 0.90, 0.90, and 0.85, respectively. Additionally, this study showed that HbA1c (P

Skin is one of the indispensable organs for life. The epidermis at the outermost surface provides a permeability barrier to infectious agents, chemicals, and excessive loss of water, while the dermis and subcutaneous tissue mechanically support the structure of the skin and appendages, including hairs and secretory glands. The integrity of the integumentary system is a key for general health, and many techniques have been developed to measure and control this protective function. In contrast, the effective skin barrier is the major obstacle for transdermal delivery and detection. Changes in the electrical properties of skin, such as impedance and ionic activity, is a practical indicator that reflects the structures and functions of the skin. For example, the impedance that reflects the hydration of the skin is measured for quantitative assessment in skincare, and the current generated across a wound is used for the evaluation and control of wound healing. Furthermore, the electrically charged structure of the skin enables transdermal drug delivery and chemical extraction. This paper provides an overview of the electrical aspects of the skin and summarizes current advances in the development of devices based on these features. [ABSTRACT FROM AUTHOR]

Hepatocytes are parenchymal cells of the liver responsible for drug detoxification, urea and bile production, serum protein synthesis, and glucose homeostasis. Hepatocytes are widely used for drug toxicity studies in bioartificial liver devices and for cell-based liver therapies. Because hepatocytes are highly differentiated cells residing in a complex microenvironment in vivo, they tend to lose hepatic phenotype and function in vitro. This paper first reviews traditional culture approaches used to rescue hepatic function in vitro and then discusses the benefits of emerging microfluidic-based culture approaches. We conclude by reviewing integration of hepatocyte cultures with bioanalytical or sensing approaches. [ABSTRACT FROM AUTHOR]

The complexity of the human brain creates significant, almost insurmountable challenges for neurological drug development. Advanced in vitro platforms are increasingly enabling researchers to overcome these challenges, by mimicking key features of the brain's composition and functionality. Many of these platforms are called "Brains-on-a-Chip"—a term that was originally used to refer to microfluidics-based systems containing miniature engineered tissues, but that has since expanded to describe a vast range of in vitro central nervous system (CNS) modeling approaches. This Perspective seeks to refine the definition of a Brain-on-a-Chip for the next generation of in vitro platforms, identifying criteria that determine which systems should qualify. These criteria reflect the extent to which a given platform overcomes the challenges unique to in vitro CNS modeling (e.g., recapitulation of the brain's microenvironment; inclusion of critical subunits, such as the blood–brain barrier) and thereby provides meaningful added value over conventional cell culture systems. The paper further outlines practical considerations for the development and implementation of Brain-on-a-Chip platforms and concludes with a vision for where these technologies may be heading. [ABSTRACT FROM AUTHOR]

The demand for ambulatory blood pressure monitoring (ABPM) is increasing due to the global rise in cardiovascular disease patients. However, conventional ABPM methods are discontinuous and can disrupt daily activities and sleep patterns. Photoplethysmography (PPG) is gaining attention from researchers due to its simplicity, portability, affordability, and ease of signal acquisition. This paper critically examines the advancements achieved in the technology of PPG-guided noninvasive blood pressure (BP) monitoring and explores future opportunities. We have performed a literature search using the Web of Science and PubMed search engines, from January 2018 to October 2023, for PPG signal quality assessment (SQA), cuffless BP estimation using single PPG, and associations between circadian rhythm and BP. Based on this foundation, we first examine the impact of PPG signal quality on blood pressure estimation results while focusing on methods for assessing PPG signal quality. Subsequently, the methods documented for estimating cuff-free BP from PPG signals are summarized. Furthermore, the study examines how individual differences affect the accuracy of BP estimation, incorporating the factors that influence arterial blood pressure (ABP) and elucidating the impact of circadian rhythm on blood pressure. Finally, there will be a summary of the study's findings and suggestions for future research directions.

The cardiovascular system demonstrates left-right (LR) asymmetry: most notably, the LR asymmetric looping of the bilaterally symmetric linear heart tube. Similarly, the orientation of the aortic arch is asymmetric as well. Perturbations to the asymmetry have been associated with several congenital heart malformations and vascular disorders. The source of the asymmetry, however, is not clear. Cell chirality, a recently discovered and intrinsic LR asymmetric cellular morphological property, has been implicated in the heart looping and vascular barrier function. In this paper, we summarize recent advances in the field of cell chirality and describe various approaches developed for studying cell chirality at multi- and single-cell levels. We also examine research progress in asymmetric cardiovascular development and associated malformations. Finally, we review evidence connecting cell chirality to cardiac looping and vascular permeability and provide thoughts on future research directions for cell chirality in the context of cardiovascular development and disease. [ABSTRACT FROM AUTHOR]

This Perspective paper advances a hypothesis of mechanosensation by endothelial cells in which the cell is a dynamic crowded system, driven by continuous enzyme activity, that can be shifted from one non-equilibrium state to another by external force. The nature of the shift will depend on the direction, rate of change, and magnitude of the force. Whether force induces a pathophysiological or physiological change in cell biology will be determined by whether the dynamics of a cellular system can accommodate the dynamics and magnitude of the force application. The complex interplay of non-static cytoskeletal structures governs internal cellular rheology, dynamic spatial reorganization, and chemical kinetics of proteins such as integrins, and a flaccid membrane that is dynamically supported; each may constitute the necessary dynamic properties able to sense external fluid shear stress and reorganize in two and three dimensions. The resulting reorganization of enzyme systems in the cell membrane and cytoplasm may drive the cell to a new physiological state. This review focuses on endothelial cell mechanotransduction of shear stress, but may lead to new avenues of investigation of mechanobiology in general requiring new tools for interrogation of mechanobiological systems, tools that will enable the synthesis of large amounts of spatial and temporal data at the molecular, cellular, and system levels. [ABSTRACT FROM AUTHOR]

Cancer, with high morbidity and high mortality, is one of the major burdens threatening human health globally. Intervention procedures via percutaneous puncture have been widely used by physicians due to its minimally invasive surgical approach. However, traditional manual puncture intervention depends on personal experience and faces challenges in terms of precisely puncture, learning-curve, safety and efficacy. The development of puncture interventional surgery robotic (PISR) systems could alleviate the aforementioned problems to a certain extent. This paper attempts to review the current status and prospective of PISR systems for thoracic and abdominal application. In this review, the key technologies related to the robotics, including spatial registration, positioning navigation, puncture guidance feedback, respiratory motion compensation, and motion control, are discussed in detail.

Novel hearable technology is securely and comfortably positioned within the ear canal minimizing inaccuracies caused by accessory movements during activities. Despite extensive research on hearable technologies within the outer ear, there is a lack of research in the field of vascular imaging and quantitative analysis in the outer ear in vivo, which is one of the crucial factors to select the appropriate sensor position. Therefore, in this paper, we introduced optical coherence tomography angiography (OCTA)-based qualitative and quantitative analyses to visualize the inner vasculature of the outer ear to acquire vascular maps for microvascular assessments in vivo. By generating maximum amplitude projection images from three-dimensional blood vascular volume, we identified variations of blood vessel signal caused by the different biological characteristics and curvature of the ear among individuals. The performance of micro-vascular mapping using the proposed method was validated through the comparison and analysis of individual vascular parameters using extracted 20 vascular-related variables. In addition, we extracted pulsatile blood flow signals, demonstrating its potential to provide photoplethysmographic signals and ear blood maps simultaneously. Therefore, our proposed OCTA-based method for ear vascular mapping successfully provides quantitative information about ear vasculature, which is potentially used for determining the position of system-on-chip sensors for health monitoring in hearable devices.

In this paper, we stimulated M1-like macrophages (obtained from U937 cells) with low-intensity pulsed ultrasound (LIPUS) to lower pro-inflammatory cytokine production. A systematic screening of different frequencies, intensities, duty cycles, and exposure times was performed. The optimal stimulation conditions leading to a marked decrease in the release of inflammatory cytokines were determined to be 38 kHz, 250 mW/cm2, 20%, and 90 min, respectively. Using these parameters, we verified that up to 72 h LIPUS did not affect cell viability, resulting in an increase in metabolic activity and in a reduction of reactive oxygen species (ROS) production. Moreover, we found that two mechanosensitive ion channels (PIEZO1 and TRPV1) were involved in the LIPUS-mediated cytokine release modulation. We also assessed the role of the nuclear factor κB (NF-κB) signaling pathway and observed an enhancement of actin polymerization. Finally, transcriptomic data suggested that the bioeffects of LIPUS treatment occur through the modulation of p38 MAPK signaling pathway.

The scientific community has shown increasing interest in laser scribing for the direct fabrication of conductive graphene-based tracks on different substrates. This can enable novel routes for the noninvasive analysis of biofluids (such as sweat or other noninvasive matrices), whose results can provide the rapid evaluation of a person's health status. Here, we present a wearable sensing platform based on laser induced graphene (LIG) porous electrodes scribed on a flexible polyimide sheet, which samples sweat through a paper sampler. The device is fully laser manufactured and features a two layer design with LIG-based vertical interconnect accesses. A detailed characterization of the LIG electrodes including pore size, surface groups, surface area in comparison to electroactive surface area, and the reduction behavior of different LIG types was performed. The bare LIG electrodes can detect the electrochemical oxidation of both uric acid and tyrosine. Further modification of the surface of the LIG working electrode with an indoaniline derivative [4-((4-aminophenyl)imino)-2,6-dimethoxycyclohexa-2,5-dien-1-one] enables the voltammetric measurement of pH with an almost ideal sensitivity and without interference from other analytes. Finally, electrochemical impedance spectroscopy was used to measure the concentrations of ions through the analysis of the sweat impedance. The device was successfully tested in a real case scenario, worn on the skin during a sports session. In vitro tests proved the non-cytotoxic effect of the device on the A549 cell line.

Hepatocytes are parenchymal cells of the liver responsible for drug detoxification, urea and bile production, serum protein synthesis, and glucose homeostasis. Hepatocytes are widely used for drug toxicity studies in bioartificial liver devices and for cell-based liver therapies. Because hepatocytes are highly differentiated cells residing in a complex microenvironment in vivo, they tend to lose hepatic phenotype and function in vitro. This paper first reviews traditional culture approaches used to rescue hepatic function in vitro and then discusses the benefits of emerging microfluidic-based culture approaches. We conclude by reviewing integration of hepatocyte cultures with bioanalytical or sensing approaches.

Skin is one of the indispensable organs for life. The epidermis at the outermost surface provides a permeability barrier to infectious agents, chemicals, and excessive loss of water, while the dermis and subcutaneous tissue mechanically support the structure of the skin and appendages, including hairs and secretory glands. The integrity of the integumentary system is a key for general health, and many techniques have been developed to measure and control this protective function. In contrast, the effective skin barrier is the major obstacle for transdermal delivery and detection. Changes in the electrical properties of skin, such as impedance and ionic activity, is a practical indicator that reflects the structures and functions of the skin. For example, the impedance that reflects the hydration of the skin is measured for quantitative assessment in skincare, and the current generated across a wound is used for the evaluation and control of wound healing. Furthermore, the electrically charged structure of the skin enables transdermal drug delivery and chemical extraction. This paper provides an overview of the electrical aspects of the skin and summarizes current advances in the development of devices based on these features.

The complexity of the human brain creates significant, almost insurmountable challenges for neurological drug development. Advanced in vitro platforms are increasingly enabling researchers to overcome these challenges, by mimicking key features of the brain's composition and functionality. Many of these platforms are called “Brains-on-a-Chip”—a term that was originally used to refer to microfluidics-based systems containing miniature engineered tissues, but that has since expanded to describe a vast range of in vitro central nervous system (CNS) modeling approaches. This Perspective seeks to refine the definition of a Brain-on-a-Chip for the next generation of in vitro platforms, identifying criteria that determine which systems should qualify. These criteria reflect the extent to which a given platform overcomes the challenges unique to in vitro CNS modeling (e.g., recapitulation of the brain's microenvironment; inclusion of critical subunits, such as the blood–brain barrier) and thereby provides meaningful added value over conventional cell culture systems. The paper further outlines practical considerations for the development and implementation of Brain-on-a-Chip platforms and concludes with a vision for where these technologies may be heading.

The cardiovascular system demonstrates left-right (LR) asymmetry: most notably, the LR asymmetric looping of the bilaterally symmetric linear heart tube. Similarly, the orientation of the aortic arch is asymmetric as well. Perturbations to the asymmetry have been associated with several congenital heart malformations and vascular disorders. The source of the asymmetry, however, is not clear. Cell chirality, a recently discovered and intrinsic LR asymmetric cellular morphological property, has been implicated in the heart looping and vascular barrier function. In this paper, we summarize recent advances in the field of cell chirality and describe various approaches developed for studying cell chirality at multi- and single-cell levels. We also examine research progress in asymmetric cardiovascular development and associated malformations. Finally, we review evidence connecting cell chirality to cardiac looping and vascular permeability and provide thoughts on future research directions for cell chirality in the context of cardiovascular development and disease.

This Perspective paper advances a hypothesis of mechanosensation by endothelial cells in which the cell is a dynamic crowded system, driven by continuous enzyme activity, that can be shifted from one non-equilibrium state to another by external force. The nature of the shift will depend on the direction, rate of change, and magnitude of the force. Whether force induces a pathophysiological or physiological change in cell biology will be determined by whether the dynamics of a cellular system can accommodate the dynamics and magnitude of the force application. The complex interplay of non-static cytoskeletal structures governs internal cellular rheology, dynamic spatial reorganization, and chemical kinetics of proteins such as integrins, and a flaccid membrane that is dynamically supported; each may constitute the necessary dynamic properties able to sense external fluid shear stress and reorganize in two and three dimensions. The resulting reorganization of enzyme systems in the cell membrane and cytoplasm may drive the cell to a new physiological state. This review focuses on endothelial cell mechanotransduction of shear stress, but may lead to new avenues of investigation of mechanobiology in general requiring new tools for interrogation of mechanobiological systems, tools that will enable the synthesis of large amounts of spatial and temporal data at the molecular, cellular, and system levels.

Recent technological breakthroughs in our ability to derive and differentiate induced pluripotent stem cells, organoid biology, organ-on-chip assays, and 3-D bioprinting have all contributed to a heightened interest in the design, assembly, and manufacture of living systems with a broad range of potential uses. This white paper summarizes the state of the emerging field of “multi-cellular engineered living systems,” which are composed of interacting cell populations. Recent accomplishments are described, focusing on current and potential applications, as well as barriers to future advances, and the outlook for longer term benefits and potential ethical issues that need to be considered.

Monitoring cell metabolism in vitro is considered a relevant methodology in several scientific fields ranging from fundamental biology research to neuro-toxicology. In the last 20 years, several in vitro neuro-pharmacological and neuro-toxicological approaches have been developed, with the intent of addressing the increasing demand for real-time, non-invasive in vitro systems capable of continuously and reliably monitoring cellular activity. In this paper, an Organic Charge Modulated Field Effect Transistor-based device is proposed as a promising tool for neuro-pharmacological applications, thanks to its ultra-high pH sensitivity and a simple fabrication technology. The preliminary characterization of this versatile organic device with primary neuronal cultures shows how these remarkable properties can be exploited for the realization of ultra-sensitive metabolic probes, which are both reference-less and low cost. These features, together with the already assessed capability of this sensor to also monitor the electrical activity of electrogenic cells, could provide important advances in the fabrication of multi-sensing lab-on-chip devices, thus opening up interesting perspectives in the neuro-pharmacological field.

Electrocardiography is a valuable tool to aid in medical understanding and treatment of heart-related ailments, specifically atrial fibrillation (AF) and other irregular cardiac behavior. Although signs of AF will manifest in conventional electrocardiogram (ECG) recordings, interpretation and localization of AF sources require significant clinical expertise. In this vein, electrocardiographic imaging has emerged as an important medical imaging modality that provides reconstructions of the heart's electrical activity from non-invasive multi-lead body-surface ECG and anatomical x-ray computed tomography images. In this paper, we present a nonlinear inversion model for computing this mapping to improve upon the reconstruction performance of current methods. While contemporary techniques typically determine an inverse solution by discretizing and inverting an underdetermined linear system of partial differential equations governing the relationship between voltage potentials of the heart and torso, the presented technique re-casts this problem as a task in function approximation and provides a direct parameterization of the inverse operator using a polynomial neural network. That is, the outlined nonlinear inversion technique is a generalization of contemporary reconstruction techniques which allows geometrical and material parameterizations of the forward-model to be optimized using real experimental data collected from patients suffering from AF, as to better represent the inverse operator with respect to reconstruction metrics applicable to electrophysiology. The accuracy of our model is evaluated against a dataset of real-patient recordings to demonstrate its validity, and mathematical analysis is provided to support the polynomial expansion used in our inversion model.

Collective motions of groups of cells are observed in many biological settings such as embryo development, tissue formation, and cancer metastasis. To effectively model collective cell movement, it is important to incorporate cell specific features such as cell size, cell shape, and cell mechanics, as well as active behavior of cells such as protrusion and force generation, contractile forces, and active biochemical signaling mechanisms that regulate cell behavior. In this paper, we develop a comprehensive model of collective cell migration in confluent epithelia based on the vertex modeling approach. We develop a method to compute cell-cell viscous friction based on the vertex model and incorporate RhoGTPase regulation of cortical myosin contraction. Global features of collective cell migration are examined by computing the spatial velocity correlation function. As active cell force parameters are varied, we found rich dynamical behavior. Furthermore, we find that cells exhibit nonlinear phenomena such as contractile waves and vortex formation. Together our work highlights the importance of active behavior of cells in generating collective cell movement. The vertex modeling approach is an efficient and versatile approach to rigorously examine cell motion in the epithelium.

Most soft biological tissues exhibit a remarkable ability to adapt to sustained changes in mechanical loads. These macroscale adaptations, resulting from mechanobiological cellular responses, are important determinants of physiological behaviors and thus clinical outcomes. Given the complexity of such adaptations, computational models can significantly increase our understanding of how contributions of different cell types or matrix constituents, and their rates of turnover and evolving properties, ultimately change the geometry and biomechanical behavior at the tissue level. In this paper, we examine relative roles of the rates of tissue responses and external loading and present a new rate-independent approach for modeling the evolution of soft tissue growth and remodeling. For illustrative purposes, we also present numerical results for arterial adaptations. In particular, we show that, for problems defined by particular characteristic times, this approximate theory captures well the predictions of a fully general constrained mixture theory at a fraction of the computational cost.

Antigen expression is an important biomarker for cell analysis and disease diagnosis. Traditionally, antigen expression is measured using a flow cytometer which, due to its cost and labor intensive sample preparation, is unsuitable to be used at the point-of-care. Therefore, an automatic, miniaturized assay which can measure antigen expression in the patient could aid in making crucial clinical decisions rapidly. Such a device would also expand the use of such an assay in basic research in biology. In this paper, we present a microfluidic device that can be used to measure antigen expression on cells. We demonstrate our approach using biotin-neutravidin as the binding pair using experimental and computational approaches. We flow beads with varying biotin surface densities (mr) through a polydimethylsiloxane channel with cylindrical pillars functionalized with neutravidin. We analyze how shear stress and collision angle, the angle at which the beads collide with the pillars, affect the angular location of beads captured on the pillars. We also find that the fraction of captured beads as a function of distance (γ) in the channel is affected by mr. Using γ, we derive the probability of capture per collision with the pillar (ε). We show that ε is linearly related to mr, which is analogous to the expression level of proteins on cell surfaces. Although demonstrated with beads, this assay can next be expanded with cells, thus paving the way for a rapid antigen expression test.

Human platelet lysates (HPLs) from allogeneic platelet concentrates (PCs) are biomaterials, which are rich in various trophic factors, increasingly used in regenerative medicine and biotherapy. Understanding how preparation methods influence the HPL protein profile, biological function, and clinical outcomes is crucial. Our study sheds light on the proteomes and functionality of different HPLs, with the aim of advancing their scientifically grounded clinical applications. To achieve this, PCs suspended in plasma underwent three distinct processing methods, resulting in seven HPL types. We used three characterization techniques: label-free proteomics and tandem mass tag (TMT)-based quantitative proteomics, both before and after the immunodepletion of abundant plasma proteins. Bioinformatic tools assessed the proteome, and western blotting validated our quantitative proteomics data. Subsequent pre-clinical studies with fluorescent labeling and label-free proteomics were used as a proof of concept for brain diffusion. Our findings revealed 1441 proteins detected using the label-free method, 952 proteins from the TMT experiment before and after depletion, and 1114 proteins from the subsequent TMT experiment on depleted HPLs. Most detected proteins were cytoplasmic, playing key roles in catalysis, hemostasis, and immune responses. Notably, the processing methodologies significantly influenced HPL compositions, their canonical pathways, and, consequently, their functionality. Each HPL exhibited specific abundant proteins, providing valuable insight for tailored clinical applications. Immunoblotting results for selected proteins corroborated our quantitative proteomics data. The diffusion and differential effects to the hippocampus of a neuroprotective HPL administered intranasally to mice were demonstrated. This proteomics study advances our understanding of HPLs, suggesting ways to standardize and customize their production for better clinical efficacy in regenerative medicine and biotherapy. Proteomic analyses also offered objective evidence that HPPL, upon intranasal delivery, not only effectively diffuses to the hippocampus but also alters protein expression in mice, bolstering its potential as a treatment for memory impairments., Competing Interests: T.B. is one co-founder of Invenis Biotherapies and is listed as the inventor on patent applications owned by Taipei Medical University and University of Lille. The authors declare that they have no known competing financial interest or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Author(s).)

Asthma is often characterized by tissue-level mechanical phenotypes that include remodeling of the airway and an increase in airway tightening, driven by the underlying smooth muscle. Existing therapies only provide symptom relief and do not improve the baseline narrowing of the airway or halt progression of the disease. To investigate such targeted therapeutics, there is a need for models that can recapitulate the 3D environment present in this tissue, provide phenotypic readouts of contractility, and be easily integrated into existing assay plate designs and laboratory automation used in drug discovery campaigns. To address this, we have developed DEFLCT, a high-throughput plate insert that can be paired with standard labware to easily generate high quantities of microscale tissues in vitro for screening applications. Using this platform, we exposed primary human airway smooth muscle cell-derived microtissues to a panel of six inflammatory cytokines present in the asthmatic niche, identifying TGF-β1 and IL-13 as inducers of a hypercontractile phenotype. RNAseq analysis further demonstrated enrichment of contractile and remodeling-relevant pathways in TGF-β1 and IL-13 treated tissues as well as pathways generally associated with asthma. Screening of 78 kinase inhibitors on TGF-β1 treated tissues suggests that inhibition of protein kinase C and mTOR/Akt signaling can prevent this hypercontractile phenotype from emerging, while direct inhibition of myosin light chain kinase does not. Taken together, these data establish a disease-relevant 3D tissue model for the asthmatic airway, which combines niche specific inflammatory cues and complex mechanical readouts that can be utilized in drug discovery efforts., Competing Interests: Yes, all authors are current or prior employees (were employees at the time of their contributions to the paper) of Novartis., (© 2023 Author(s).)