ChatGPT, a language model developed by OpenAI, has the potential to play a role in public health. With its ability to generate human-like text based on large amounts of data, ChatGPT has the potential to support individuals and communities in making informed decisions about their health (Panch et al. Lancet Digit Health 1:e13-e14, 2019; Baclic et al. Canada Commun Dis Rep 46.6:161, 2020). However, as with any technology, there are limitations and challenges to consider when using ChatGPT in public health. In this overview, we will examine the potential uses of ChatGPT in public health, as well as the advantages and disadvantages of its use.

Obesity has become a serious global health problem. For some patients who cannot be treated with traditional methods, artificial intelligence technologies are a new source of hope. Chat GPT is a language model that has become popular in recent times and has many applications in natural language processing. This article focuses on the potential use of Chat GPT in obesity treatment. Chat GPT can provide personalized recommendations on topics, such as nutrition plans, exercise programs, and psychological support. In this way, a personalized treatment plan can be created based on the individual needs of patients and a more effective approach to obesity treatment can be achieved. However, some ethical and security concerns should also be considered regarding the use of this technology. In conclusion, the potential of Chat GPT in obesity treatment is promising, and with the effective use of this technology, better results can be achieved in obesity treatment.

Cell tracking algorithms have been used to extract cell counts and motility information from time-lapse images of migrating cells. However, these algorithms often fail when the collected images have cells with spatially and temporally varying features, such as morphology, position, and signal-to-noise ratio. Consequently, state-of-the-art algorithms are not robust or reliable because they require manual inputs to overcome the cell feature changes. To address these issues, we present a fully automated, adaptive, and robust feature-based cell tracking algorithm for the accurate detection and tracking of cells in time-lapse images. Our algorithm tackles measurement limitations twofold. First, we use Hessian filtering and adaptive thresholding to detect the cells in images, overcoming spatial feature variations among the existing cells without manually changing the input thresholds. Second, cell feature parameters are measured, including position, diameter, mean intensity, area, and orientation, and these parameters are simultaneously used to accurately track the cells between subsequent frames, even under poor temporal resolution. Our technique achieved a minimum of 92% detection and tracking accuracy, compared to 16% from Mosaic and Trackmate. Our improved method allows for extended tracking and characterization of heterogeneous cell behavior that are of particular interest for intravital imaging users.

Bowel cancer is a multifactorial disease arising from a combination of genetic predisposition and environmental factors. Detection of bowel cancer and its precursor lesions is predominantly performed by either visual inspection of the colonic mucosa during endoscopy or cross-sectional imaging. Most cases are diagnosed when the cancer is already at an advanced stage. These modalities are less reliable for detecting lesions at the earliest stages, when they are typically small or flat. Removal of lesions at the earliest possible stage reduces the risk of cancer death, which is largely due to a reduced risk of subsequent metastasis. In this review, we summarised the origin of bowel cancer and the mechanism of its metastasis. In particular, we reviewed a broad spectrum of literatures covering the biomechanics of bowel cancer and its measurement techniques that are pertinent to the successful development of a bowel cancer diagnostic device. We also reviewed existing bowel cancer diagnostic techniques that are available for clinical use. Finally, we outlined current clinical needs and highlighted the potential roles of medical robotics on early bowel cancer diagnosis.

Cryosurgery is a minimally invasive approach to the treatment of focal prostate cancer (PCa). A major complication is the cryoinjury to the cavernous nerve in the neurovascular bundle (NVB). This nerve cryoinjury halts conduction of action potentials (APs) and can eventually result in erectile dysfunction and therefore diminished quality of life for the patient. Here, we propose the application of cryoprotective agents (CPA) to the regions of the nerves in the NVB, prior to prostate cryosurgery, to minimize non-recoverable loss of AP conduction. We modeled a cryosurgical procedure based on data taken during a clinical case and applied ex-vivo porcine phrenic nerves and rat sciatic nerve with temperature profile of NVB. The APs were measured before and after the CPA exposures and during 3 h of recovery. Comparisons of AP amplitude recovery with various CPA compositions reveal that certain CPAs (e.g., 5% DMSO + 7.5% Trehalose and 5% M22 for porcine and rat nerves, respectively) showed little or no toxicity and effective cryoprotection from freezing (on average 48% and 30% of recovered AP, respectively). In summary, we demonstrate that neural conduction can be preserved after exposure to freezing conditions if CPAs are properly selected and deployed onto the nerve.

As the first clinically translated machine-neural interface, cochlear implants (CI) have demonstrated much success in providing hearing to those with severe to profound hearing loss. Despite their clinical effectiveness, key drawbacks such as hearing damage, partly from insertion forces that arise during implantation, and current spread, which limits focussing ability, prevent wider CI eligibility. In this review, we provide an overview of the anatomical and physical properties of the cochlea as a resource to aid the development of accurate models to improve future CI treatments. We highlight the advancements in the development of various physical, animal, tissue engineering, and computational models of the cochlea and the need for such models, challenges in their use, and a perspective on their future directions.

Implantable tissue-engineered vascular grafts (TEVGs) usually trigger the host reaction which is inextricably linked with the immune system, including blood-material interaction, protein absorption, inflammation, foreign body reaction, and so on. With remarkable progress, the immune response is no longer considered to be entirely harmful to TEVGs, but its therapeutic and impaired effects on angiogenesis and tissue regeneration are parallel. Although the implicated immune mechanisms remain elusive, it is certainly worthwhile to gain detailed knowledge about the function of the individual immune components during angiogenesis and vascular remodeling. This review provides a general overview of immune cells with an emphasis on macrophages in light of the current literature. To the extent possible, we summarize state-of-the-art approaches to immune cell regulation of the vasculature and suggest that future studies are needed to better define the timing of the activity of each cell subpopulation and to further reveal key regulatory switches.

Bone morphogenetic protein 4 (BMP4) is emerging as a promising cytokine for regenerative medicine and tissue engineering. BMP4 has been shown to promote the regeneration of teeth, periodontal tissue, bone, cartilage, the thymus, hair, neurons, nucleus pulposus, and adipose tissue, as well as the formation of skeletal myotubes and vessels. BMP4 can also contribute to the formation of tissues in the heart, lung, and kidney. However, there are certain deficiencies, including the insufficiency of the mechanism of BMP4 in some fields and an appropriate carrier of BMP4 for clinical use. There has also been a lack of in vivo experiments and orthotopic transplantation studies in some fields. BMP4 has great distance from the clinical application. Therefore, there are many BMP4-related studies waiting to be explored. This review mainly discusses the effects, mechanisms, and applications of BMP4 in regenerative medicine and tissue engineering over the last 10 years in various domains and possible improvements. BMP4 has shown great potential in regenerative medicine and tissue engineering. The research of BMP4 has broad development space and great value.

For certain types of cancer patients, ovarian transplantation has a risk of malignant cancer cell infection. However, the autologous transplantation of an artificial ovary is safe and effective, guarantees the normal development of isolated follicles, regular oocyte maturation, and ovulation, partially restores endocrine function, and enables the patient to regain reproductive ability. Despite the complexity of the natural ovary, some progress has been made in the repair or replacement of reproductive tissues with the use of various biomaterials. This article reviews the physical structure, biomechanical properties, design elements, preparation routes, construction and practical use of natural polymer materials, usually hydrogel scaffolds, such as alginate, fibrin, gelatin, collagen, agarose, and acellular ovarian matrix in the preparation of artificial ovaries. We summarize how these materials can be made into artificial ovaries to achieve the conditions for fertility through follicle and oocyte development and identify several major issues to overcome for the future development of artificial ovaries, including how to establish blood recirculation, and how to establish hormone synthesis and release channels. This review is intended to provide a reference for the use of natural polymer biomaterials in reproductive clinics.

Bioprinting is an innovative and emerging technology of additive manufacturing (AM) and has revolutionized the biomedical sector by printing three-dimensional (3D) cell-laden constructs in a precise and controlled manner for numerous clinical applications. This approach uses biomaterials and varying types of cells to print constructs for tissue regeneration, e.g., cardiac, bone, corneal, cartilage, neural, and skin. Furthermore, bioprinting technology helps to develop drug delivery and wound healing systems, bio-actuators, bio-robotics, and bio-sensors. More recently, the development of four-dimensional (4D) bioprinting technology and stimuli-responsive materials has transformed the biomedical sector with numerous innovations and revolutions. This issue also leads to the exponential growth of the bioprinting market, with a value over billions of dollars. The present study reviews the concepts and developments of 3D and 4D bioprinting technologies, surveys the applications of these technologies in the biomedical sector, and discusses their potential research topics for future works. It is also urged that collaborative and valiant efforts from clinicians, engineers, scientists, and regulatory bodies are needed for translating this technology into the biomedical, pharmaceutical, and healthcare systems.

The digital world has recently experienced a swift rise in worldwide popularity due to Virtual (VR) and Augmented Reality (AR) devices. However, concrete evidence about the effects of VR/AR devices on the physical workload imposed on the human body is lacking. We reviewed 27 articles that evaluated the physical impact of VR/AR-based tasks on the users using biomechanical sensing equipment and subjective tools. Findings revealed that movement and muscle demands (neck and shoulder) varied in seven and five studies while using VR, while in four and three studies during AR use, respectively, compared to traditional methods. User discomfort was also found in seven VR and three AR studies. Outcomes indicate that interface and interaction design, precisely target locations (gestures, viewing), design of virtual elements, and device type (location of CG as in Head-Mounted Displays) influence these alterations in neck and shoulder regions. Recommendations based on the review include developing comfortable reach envelopes for gestures, improving wearability, and studying temporal effects of repetitive movements (such as effects on fatigue and stability). Finally, a guideline is provided to assist researchers in conducting effective evaluations. The presented findings from this review could benefit designers/evaluations working towards developing more effective VR/AR products.

Intracerebral hemorrhage (ICH) is a stroke subtype with high mortality and disability, and there are no proven medical treatments that can improve the functional outcome of ICH patients. Robot-assisted neurosurgery is a significant advancement in the development of minimally invasive surgery for ICH. This review encompasses the latest advances and future directions of surgical robots for ICH. First, three robotic systems for neurosurgery applied to ICH are illustrated. Second, the key technologies of robot-assisted surgery for ICH are introduced in aspects of stereotactic technique and navigation, the puncture instrument, and hematoma evacuation. Finally, the limitations of current surgical robots are summarized, and the possible development direction is discussed, which is named "multisensor fusion and intelligent aspiration control of minimally invasive surgical robot for ICH". It is expected that the new generation of surgical robots for ICH will facilitate quantitative, precise, individualized, standardized treatment strategies for ICH.

Reactive hyperemia is a well-established technique for the non-invasive evaluation of the peripheral microcirculatory function, measured as the magnitude of limb re-perfusion after a brief period of ischemia. Despite widespread adoption by researchers and clinicians alike, many uncertainties remain surrounding interpretation, compounded by patient-specific confounding factors (such as blood pressure or the metabolic rate of the ischemic limb). Mathematical modeling can accelerate our understanding of the physiology underlying the reactive hyperemia response and guide in the estimation of quantities which are difficult to measure experimentally. In this work, we aim to provide a comprehensive guide for mathematical modeling techniques that can be used for describing the key phenomena involved in the reactive hyperemia response, alongside their limitations and advantages. The reported methodologies can be used for investigating specific reactive hyperemia aspects alone, or can be combined into a computational framework to be used in (pre-)clinical settings.

Industrial tasks that involve frequent sitting/standing transitions and squatting activities can benefit from lower-limb industrial exoskeletons; however, their use is not as widespread as their upper-body counterparts. In this review, we examined 23 articles that evaluated the effects of using Wearable Chair (WC) and Squat-assist (SA) exoskeletons. Evaluations mainly included assessment of muscular demands in the thigh, shank, and upper/lower back regions. Both types of devices were found to lessen muscular demands in the lower body by 30-90%. WCs also reduced low-back demands (~ 37%) and plantar pressure (54-80%) but caused discomfort/unsafe feeling in participants. To generalize outcomes, we suggest standardizing approaches used for evaluating the devices. Along with addressing low adoption through design upgrades (e.g., ground and body supports/attachments), we recommend that researchers thoroughly evaluate temporal effects on muscle fatigue, metabolic rate, and stability of wearers. Although lower-limb exoskeletons were found to be beneficial, discrepancies in experimental protocols (posture/task/measures) were discovered. We also suggest simulating more realistic conditions, such as walking/sitting interchangeability for WCs and lifting loads for SA devices. The presented outcomes could help improve the design/evaluation approaches, and implementation of lower limb wearable devices across industries.

Musculotendon parameters are key factors in the Hill-type muscle contraction dynamics, determining the muscle force estimation accuracy of a musculoskeletal model. Their values are mostly derived from muscle architecture datasets, whose emergence has been a major impetus for model development. However, it is often not clear if such parameter update indeed improves simulation accuracy. Our goal is to explain to model users how these parameters are derived and how accurate they are, as well as to what extent errors in parameter values might influence force estimation. We examine in detail the derivation of musculotendon parameters in six muscle architecture datasets and four prominent OpenSim models of the lower limb, and then identify simplifications which could add uncertainties to the derived parameter values. Finally, we analyze the sensitivity of muscle force estimation to these parameters both numerically and analytically. Nine typical simplifications in parameter derivation are identified. Partial derivatives of the Hill-type contraction dynamics are derived. Tendon slack length is determined as the musculotendon parameter that muscle force estimation is most sensitive to, whereas pennation angle is the least impactful. Anatomical measurements alone are not enough to calibrate musculotendon parameters, and the improvement on muscle force estimation accuracy will be limited if the source muscle architecture datasets are the only main update. Model users may check if a dataset or model is free of concerning factors for their research or application requirements. The derived partial derivatives may be used as the gradient for musculotendon parameter calibration. For model development, we demonstrate that it is more promising to focus on other model parameters or components and seek alternative strategies to further increase simulation accuracy.

The advent of artificial intelligence (AI), particularly ChatGPT/GPT-4, has led to advancements in various fields, including healthcare. This study explores the prospective role of ChatGPT/GPT-4 in various facets of spinal surgical practice, especially in supporting spinal surgeons during the perioperative management of endoscopic spinal surgery for patients with lumbar disc herniation. The AI-driven chatbot can facilitate communication between spinal surgeons, patients, and their relatives, streamline the collection and analysis of patient data, and contribute to the surgical planning process. Furthermore, ChatGPT/GPT-4 may enhance intraoperative support by providing real-time surgical navigation information and physiological parameter monitoring, as well as aiding in postoperative rehabilitation guidance. However, the appropriate and supervised use of ChatGPT/GPT-4 is essential, considering the potential risks associated with data security and privacy. The study concludes that ChatGPT/GPT-4 can serve as a valuable lighthouse for spinal surgeons if used correctly and responsibly.

Climate change is a major global challenge that requires the integration of many different scientific disciplines, including atmospheric science, oceanography, and ecology. The complexity and scale of the problem require sophisticated tools and techniques to understand, model, and project future climate conditions. Artificial intelligence and natural language processing technologies, such as ChatGPT, have the potential to play a critical role in advancing our understanding of climate change and improving the accuracy of climate projections. ChatGPT can be used in a variety of ways to aid climate research, including in model parameterization, data analysis and interpretation, scenario generation, and model evaluation. This technology provides researchers and policy-makers with a powerful tool for generating and analyzing different climate scenarios based on a wide range of data inputs, and for improving the accuracy of climate projections. The author acknowledges asking chatGPT questions regarding its uses for Climate Change Research. Some of the uses that it states are possible now and some are potentials for the future. The author has analyzed and edited the replies of chat GPT.

Research on human posture and balance control has grown in recent years, leading to continued advances in their understanding. The ability to maintain balance is attributed to the interplay of the visual, vestibular, and somatosensory systems, although an important role is also played by the auditory system. The lack or deficit in any of these systems leads to a reduced stability that may be counterbalanced by the integration of all the remaining sensory information. Auditory and vibratory stimulation have been found to be useful to enhance balance alongside daily activities either in healthy or pathological subjects; nevertheless, while widely investigated, the literature relating to these approaches is still fragmented. This review aims at addressing this by collecting, organising, and discussing all the literature to date on the effects of the various acoustic and vibratory stimulation techniques available on static upright posture in healthy subjects. In addition, this review intends to provide a solid and comprehensive starting point for all the researchers interested in these research areas. A systematic search of the literature was performed and a total of 33 articles (24 on vibratory stimulation and 9 on acoustic stimulation) were included in our analysis. For all articles, several elements were highlighted including: the study sample, the characteristics of the stimulations, the recording instruments, the experimental protocols, and outcomes. Overall, both stimulations analysed were found to have a positive effect on balance but more research is needed to align those alternative approaches to the traditional ones.

Face masks have been proven to be medicine's best public health tool for preventing transmission of airborne pathogens. However, in situations with continuous exposure, lower quality and "do-it-yourself" face masks cannot provide adequate protection against pathogens, especially when mishandled. In addition, the use of multiple face masks each day places a strain on personal protective equipment (PPE) supply and is not environmentally sustainable. Therefore, there is a significant clinical and commercial need for a reusable, pathogen-inactivating face mask. Herein, we propose adding quaternary poly(dimethylaminohexadecyl methacrylate), q(PDMAHDM), abbreviated to q(PDM), to existing fabric networks to generate "contact-killing" face masks-effectively turning cotton, polypropylene, and polyester into pathogen resistant materials. It was found that q(PDM)-integrated face masks were able to inactivate both Gram-positive and Gram-negative bacteria in liquid culture and aerosolized droplets. Furthermore, q(PDM) was electrospun into homogeneous polymer fibers, which makes the polymer practical for low-cost, scaled-up production.

Head injuries are common for cyclists involved in collisions. Such collision scenarios result in a range of injuries, with different head impact speeds, angles, locations, or surfaces. A clear understanding of these collision characteristics is vital to design high fidelity test methods for evaluating the performance of helmets. We review literature detailing real-world cyclist collision scenarios and report on these key characteristics. Our review shows that helmeted cyclists have a considerable reduction in skull fracture and focal brain pathologies compared to non-helmeted cyclists, as well as a reduction in all brain pathologies. The considerable reduction in focal head pathologies is likely to be due to helmet standards mandating thresholds of linear acceleration. The less considerable reduction in diffuse brain injuries is likely to be due to the lack of monitoring head rotation in test methods. We performed a novel meta-analysis of the location of 1809 head impacts from ten studies. Most studies showed that the side and front regions are frequently impacted, with one large, contemporary study highlighting a high proportion of occipital impacts. Helmets frequently had impact locations low down near the rim line. The face is not well protected by most conventional bicycle helmets. Several papers determine head impact speed and angle from in-depth reconstructions and computer simulations. They report head impact speeds from 5 to 16 m/s, with a concentration around 5 to 8 m/s and higher speeds when there was another vehicle involved in the collision. Reported angles range from 10° to 80° to the normal, and are concentrated around 30°-50°. Our review also shows that in nearly 80% of the cases, the head impact is reported to be against a flat surface. This review highlights current gaps in data, and calls for more research and data to better inform improvements in testing methods of standards and rating schemes and raise helmet safety.

Accurate needle targeting is critical for many clinical procedures, such as transcutaneous biopsy or radiofrequency ablation of tumors. However, targeting errors may arise, limiting the widespread adoption of these procedures. Advances in flexible needle (FN) steering are emerging to mitigate these errors. This review summarizes the state-of-the-art developments of FNs and addresses possible targeting errors that can be overcome with steering actuation techniques. FN steering techniques can be classified as passive and active. Passive steering directly results from the needle-tissue interaction forces, whereas active steering requires additional forces to be applied at the needle tip, which enhances needle steerability. Therefore, the corresponding targeting errors of most passive FNs and active FNs are between 1 and 2 mm, and less than 1 mm, respectively. However, the diameters of active FNs range from 1.42 to 12 mm, which is larger than the passive steering needle varying from 0.5 to 1.4 mm. Therefore, the development of active FNs is an area of active research. These active FNs can be steered using tethered internal direct actuation or untethered external actuation. Examples of tethered internal direct actuation include tendon-driven, longitudinal segment transmission and concentric tube transmission. Tendon-driven FNs have various structures, and longitudinal segment transmission needles could be adapted to reduce tissue damage. Additionally, concentric tube needles have immediate advantages and clinical applications in natural orifice surgery. Magnetic actuation enables active FN steering with untethered external actuation and facilitates miniaturization. The challenges faced in the fabrication, sensing, and actuation methods of FN are analyzed. Finally, bio-inspired FNs may offer solutions to address the challenges faced in FN active steering mechanisms.

ChatGPT has been a frequent topic of discussion lately. All over the Internet, from YouTube to blogs, there have been reports about how ChatGPT is able to plan people's daily activities, even for a whole month. However, what matters is what activities ChatGPT recommends. When ChatGPT was trained on a vast amount of data from the Internet, we wondered if it would suggest activities that can lead to addiction. In our test, not once did ChatGPT recommend an activity related to alcohol, drug use, or any other activity that can lead to addiction with serious health consequences. Suggestions seemed more like self-improvement posts on blogs than discussion forums where people might mention drinking in the evenings. Thus, if a person were to use ChatGPT as a personal lifestyle advisor, it does not appear on the basis of this test that ChatGPT would recommend activities that would be fundamentally detrimental to their health. However, more detailed long-term testing of similar tools is needed before recommendations for use in practice can be made.

Although intensive care medicine (ICM) is a relatively young discipline, it has rapidly developed into a full-fledged and highly specialized specialty covering several fields of medicine. The COVID-19 pandemic led to a surge in intensive care unit demand and also bring unprecedented development opportunities for this area. Multiple new technologies such as artificial intelligence (AI) and machine learning (ML) were gradually being applied in this field. In this study, through an online survey, we have summarized the potential uses of ChatGPT/GPT-4 in ICM range from knowledge augmentation, device management, clinical decision-making support, early warning systems, and establishment of intensive care unit (ICU) database.

This article aims to answer frequently asked questions about the Covid-19 pandemic using ChatGPT and contribute to the spread of accurate information about the pandemic. The article provides general information about the ways Covid-19 is spread, symptoms, diagnosis, treatment, vaccines and pandemic management. It also provides advice on infection control, vaccination campaigns and emergency preparedness.

The use of ovine animal models in the study of injury biomechanics and modeling is increasing, due to their favorable size and other physiological characteristics. Along with this increase, there has also been increased interest in the development of in silico ovine models for computational studies to compliment physical experiments. However, there remains a gap in the literature characterizing the morphological and mechanical characteristics of ovine ribs. The objective of this study therefore is to report anatomical and mechanical properties of the ovine ribs using microtomography (micro-CT) and two types of mechanical testing (quasi-static bending and dynamic tension). Using microtomography, young ovine rib samples obtained from a local abattoir were cut into approximately fourteen 38 mm sections and scanned. From these scans, the cortical bone thickness and cross-sectional area were measured, and the moment of inertia was calculated to enhance the mechanical testing data. Based on a standard least squares statistical model, the cortical bone thickness varied depending on the region of the cross-section and the position along the length of the rib (p < 0.05), whereas the cross-sectional area remained consistent (p > 0.05). Quasi-static three-point bend testing was completed on ovine rib samples, and the resulting force-displacement data was analyzed to obtain the stiffness (44.67 ± 17.65 N/mm), maximum load (170.54 ± 48.28 N) and displacement at maximum load (7.19 ± 2.75 mm), yield load (167.81 ± 48.12 N) and displacement at yield (6.10 ± 2.25 mm), and the failure load (110.90 ± 39.30 N) and displacement at failure (18.43 ± 2.10 mm). The resulting properties were not significantly affected by the rib (p > 0.05), but by the animal they originated from (p < 0.05). For the dynamic testing, samples were cut into coupons and tested in tension with an average strain rate of 18.9 strain/sec. The resulting dynamic testing properties of elastic modulus (5.16 ± 2.03 GPa), failure stress (63.29 ± 14.02 MPa), and failure strain (0.0201 ± 0.0052) did not vary based on loading rate (p > 0.05).

Cancer progression is closely related to changes in the structure and mechanical properties of the tumor microenvironment (TME). In many solid tumors, including pancreatic cancer, the interplay among the different components of the TME leads to a desmoplastic reaction mainly due to collagen overproduction. Desmoplasia is responsible for the stiffening of the tumor, poses a major barrier to effective drug delivery and has been associated with poor prognosis. The understanding of the involved mechanisms in desmoplasia and the identification of nanomechanical and collagen-based properties that characterize the state of a particular tumor can lead to the development of novel diagnostic and prognostic biomarkers. In this study, in vitro experiments were conducted using two human pancreatic cell lines. Morphological and cytoskeleton characteristics, cells' stiffness and invasive properties were assessed using optical and atomic force microscopy techniques and cell spheroid invasion assay. Subsequently, the two cell lines were used to develop orthotopic pancreatic tumor models. Tissue biopsies were collected at different times of tumor growth for the study of the nanomechanical and collagen-based optical properties of the tissue using Atomic Force Microscopy (AFM) and picrosirius red polarization microscopy, respectively. The results from the in vitro experiments demonstrated that the more invasive cells are softer and present a more elongated shape with more oriented F-actin stress fibers. Furthermore, ex vivo studies of orthotopic tumor biopsies on MIAPaCa-2 and BxPC-3 murine tumor models highlighted that pancreatic cancer presents distinct nanomechanical and collagen-based optical properties relevant to cancer progression. The stiffness spectrums (in terms of Young's modulus values) showed that the higher elasticity distributions were increasing during cancer progression mainly due desmoplasia (collagen overproduction), while a lower elasticity peak was evident - due to cancer cells softening - on both tumor models. Optical microscopy studies highlighted that collagen content increases while collagen fibers tend to form align patterns. Consequently, during cancer progression nanomechanical and collagen-based optical properties alter in relation to changes in collagen content. Therefore, they have the potential to be used as novel biomarkers for assessing and monitoring tumor progression and treatment outcomes.

This study used finite element models to investigate the efficacy of seated pedestrian protection equipment in vehicle impacts. The selected safety equipment, a lap belt, an airbag vest, and a bicycle helmet, were chosen to mitigate the underlying biomechanical causes of seated pedestrian injuries reported in the literature. The impact conditions were based on the three most dangerous impact scenarios from a previous seated pedestrian impact study. Serious injury (AIS 3+) risks were compared with and without protective equipment. A 50th percentile male occupant model and two generic vehicle models, the family car (FCR) and sports utility vehicle (SUV), were used to simulate vehicle collisions. Three impact conditions were run with every combination of protective equipment (n = 24). The helmet reduced head and brain injury risks from the vehicle-head and ground-head contacts. The airbag reduced the head injury risk in the FCR vehicle-head contact but increased the brain injury risks in the SUV impacts from increased whiplash. The lap belt increased head injury risks for both the FCR and the SUV impacts because it created a stronger FCR vehicle-head contact and SUV ground-head contact. When the belt and airbag were used together the head injury risks dramatically decreased because the pedestrian body impacted the ground arm or leg first and slowly rolled onto the ground which resulted in softer ground-head contacts and in two instances, no ground-head contact. Only the helmet proved effective in all impact conditions. Future testing must be completed before recommending the belt or airbag for seated pedestrians.

This paper describes a cancer detection procedure based on customised electrical impedance spectroscopy (EIS) in breast cancer surgical samples and an analysis of its outcomes. A tissue analyser was developed to inject a low-amplitude alternating current with penetrating electrodes into breast specimens along a broad spectrum of frequencies. Experimental measurements were carried out on more than one hundred excised breast cancer specimens, with the goal of discriminating between the tumour and surrounding non-neoplastic tissue. The probe was inserted in different locations immediately after surgical excision in order to measure tissue impedance (modulus and phase). Electrical impedance varied significantly between neoplastic and surrounding non-neoplastic tissues, with a low standard deviation among the different measurements, confirming good reproducibility. Tumours could be discriminated from non-neoplastic tissues according to their impedance modulus value for high frequencies and phase value for low frequencies. Impedance also varied significantly in both non-neoplastic and tumour tissues depending on the patient's age and tumour characteristics, such as size and histological sub-type. EIS is able to discriminate between healthy tissue and cancer. Future developments of this technology could be exploited for intraoperative real-time evaluation of the transition zone between cancer and normal tissues.

The maritime industry is vital to international trade, however, it also poses inimitable challenges to the health and well-being of mariners. Long voyages at sea might make it grim to receive high-quality healthcare. This is a descriptive study that highlights the use of ChatGPT in providing healthcare amenities to mariners. AI technologies can revolutionize maritime healthcare to tackle this issue. ChatGPT, a state-of-the-art AI system developed by OpenAI can provide valuable support for the health and welfare of seafarers'. By harnessing the extensive expertise and conversational capacities of ChatGPT, maritime industries can provide personalized and prompt healthcare services to their stakeholders. This research work will highlight how ChatGPT-powered healthcare services can boost the health and well-being of seafarers. ChatGPT has the potential to revolutionize the marine sector by enabling virtual consultations with healthcare professionals for the analysis of health data. The assimilation of ChatGPT technology into maritime healthcare has the potential to revolutionize the way seafarers receive care and support. Certainly, some challenges need to be taken into consideration.

Generative Pre-trained Transformer-based Chatbot (ChatGPT) is an emerging OpenAI application with its greater role in revolutionizing the world. ChatGPT can generate a massive amount of data by using the simple textual input. ChatGPT has its role in supporting the communities to make deciding role in healthcare sector. This paper aims to provide information about monkey pox (mpox) infection in Pakistan. Moreover, this paper analyzes the text-based information given by ChatGPT and narrates potential advantages and disadvantages about mpox infection. Spread of infection, symptoms and diagnose of mpox, control and management, and government responsibilities are major identified advantages. Findings of this paper also show some potential issues of ChatGPT AI application, which are as lack of latest data about mpox in Pakistan, reliability and performance issues, cost and resources for appropriate development and implementation of Open AI application in healthcare. Future works can be carried out to address these limitations in ChatGPT AI application.

Sports medicine, an essential branch of orthopedics, focuses on preserving, restoring, improving, and rebuilding the function of the human motor system. As a thriving interdisciplinary field, sports medicine attracts not only the interest of the orthopedic community, but also artificial intelligence (AI). In this study, our team summarized the potential applications of GPT-4 in sports medicine including diagnostic imaging, exercise prescription, medical supervision, surgery treatment, sports nutrition, and science research. In our opinion, it is impossible that GPT-4 could make sports physicians obsolete. Instead, it could become an indispensable scientific assistant for sport doctors in future.

Biomedical engineering is a relatively young interdisciplinary field based on engineering, biology, and medicine. Of note, the rapid progress of artificial intelligence (AI)-based technologies has made a significant impact on the biomedical engineering field, and continuously bring innovations and breakthroughs. Recently, ChatGPT, an AI chatbot developed by OpenAI company, has gained tremendous attention due to its powerful natural language generation and understanding ability. In this study, we explored potential of GPT-4 in the eight branches of biomedical engineering including medical imaging, medical devices, bioinformatics, biomaterials, biomechanics, gene and cell engineering, tissue engineering, and neural engineering. Our results show that the application of GPT-4 will bring new opportunities for the development of this field.

In order to study the influence of different vascular stenosis rates and stent-to-artery ratios on the fatigue strength and reliability of lower limb arterial stents, numerical simulation was conducted for the fatigue strength of complete SE stents under pulsating loads using a finite element method. Then, fracture mechanics and conditional probability theory were adopted for mathematical modeling, whereby analyzing the crack growth rate and reliability with stents of different thickness (0.12, 0.15, and 0.18 mm) at different vascular stenosis rates (30, 50, and 70%) and stent-to-artery ratios (80, 85, and 90%). The study found: all three stents of different thickness failed to meet 10-year service life at three vascular stenosis rates; all three stents of different thickness met 10-year service life at three stent-to-artery ratios. With increased vascular stenosis rate, the elastic strain of stents was increased, while the fatigue strength was decreased; with increased stent-to-artery ratio, the elastic strain of the stent was increased, while the reliability of the stent was reduced. After the stent with an initial crack was implanted into the vessel, the crack length underwent non-linear growth with increased pulsating cyclic loads. When the pulsating load reached 3 × 108, the growth rate of the crack on the stent surface increased exponentially, leading to a rapid decrease in reliability. Vascular stenosis rate, stent release ratio, and support thickness have significant effects on crack length propagation rate and reliability. Determining the influence of vascular stenosis rate and stent-to-artery ratio on the fatigue strength and reliability of stents provides a valuable reference for evaluating the fracture failure rate and safety of stents.

Colorectal surgery is a specialized branch of surgery that involves the diagnosis and treatment of conditions affecting the colon, rectum, and anus. In the recent years, the use of artificial intelligence (AI) has gained considerable interest in various medical specialties, including surgery. Chatbot Generative Pre-Trained Transformer (ChatGPT), an AI-based chatbot developed by OpenAI, has shown great potential in improving the quality of healthcare delivery by providing accurate and timely information to both patients and healthcare professionals. In this paper, we investigate the potential application of ChatGPT in colorectal surgery. We also discuss the potential advantages and challenges associated with the implementation of ChatGPT in the surgical setting. Furthermore, we address the socio-ethical implications of utilizing ChatGPT in healthcare. This includes concerns over patient privacy, liability, and the potential impact on the doctor-patient relationship. Our findings suggest that ChatGPT has the potential to revolutionize the field of colorectal surgery by providing personalized and precise medical information, reducing errors and complications, and improving patient outcomes.

Over the past month, a new AI model called Chatbot Generative Pre-trained Transformer (ChatGPT), has received enormous attention in the media and scientific communities due to its ability to process and respond to commands in a humanistic fashion. As reported, five days after its launch, the number of registered users of ChatGPT exceeded one million, and its monthly active users had exceeded 100 million two months later, making it the most rapidly growing consumer application in history. The advent of ChatGPT has further brought about new ideas and challenges in the realm of infectious disease. In view of this, in order to evaluate the potential use of ChatGPT in clinical practice and scientific research of infectious disease, we conducted a brief online survey by using the publicly available ChatGPT webpage. Also, the present study also talks about the relevant social and ethical issues related to this program.

In the era of big data, generative artificial intelligence (AI) models are currently in a boom. The Chatbot Generative Pre-trained Transformer (ChatGPT), a large language model (LLM) developed by OpenAI (San Francisco, CA), is a type of AI software that could generate text based on the input it receives. In this study, in order to explore how ChatGPT could give reflections and suggestions about the sudden outbreak of Mpox in 2022 from the AI dimensions, our group talked with ChatGPT with several questions about Mpox. We hope this talk could enrich our knowledge on Mpox from the new AI dimensions and also explore the possibility of human and AI fight shoulder to shoulder for prevention and containment of the potential epidemics or pandemics in future.

Muscle structure is an essential component in typical computational models of the musculoskeletal system. Almost all musculoskeletal models represent muscle geometry using a set of line segments. The straight-line approach limits models' ability to accurately predict the paths of muscles with complex geometry. This approach needs knowledge of how the muscle changes shape and interacts with fundamental structures like muscles, bones, and joints that move. Moreover, the moment arms are supposed to be equivalent to all the fibers in the muscle. This study aims to create a shoulder musculoskeletal model that includes complex muscle geometries. We reconstructed the shape of fibers in the entire volume of six muscles adjacent to the shoulder using an automated technique. This method generates many fibers from the surface geometry of the skeletal muscle and its attachment areas. Highly discretized muscle representations for all muscles were created and used to simulate different shoulder movements. The moment arms of each muscle were calculated and validated against cadaveric measurements and models of the same muscles from the literature. We found that simulations using the developed musculoskeletal models generated more realistic geometries, which expands the physical representation of muscles compared to line segments. The shoulder musculoskeletal model with complex muscle geometry is created to increase the anatomical reality of models and the lines action of muscle fibers, and to be used for finite element investigations.

The collagen network is the highly organized backbone of articular cartilage providing tissue tensile stiffness and restricting proteoglycan bleaching out of the tissue. Osteoarthritis (OA) diminishes proper collagen network adaptation. Our aim was to provide quantitative three-dimensional (3D) information of the cartilage collagen network adaptation in early osteoarthritis using high resolution micro-computed tomography (µCT)-imaging. Osteochondral samples from the femoral condyles were collected from healthy (N = 8, both legs) and experimental OA rabbit model with anterior cruciate ligament transection (N = 14, single leg). Samples were processed for cartilage µCT-imaging and histological evaluation with polarized light microscopy (PLM). Structure tensor analysis was used to analyse the collagen fibre orientation and anisotropy of the µCT-images, and PLM was used as a validation for structural changes. Depth-wise comparison of collagen fibre orientation acquired with µCT-imaging and PLM correlated well, but the values obtained with PLM were systematically greater than those measured with µCT-imaging. Structure tensor analysis allowed for 3D quantification of collagen network anisotropy. Finally, µCT-imaging revealed only minor differences between the control and experimental groups.

The left atrial appendage (LAA) causes 91% of thrombi in atrial fibrillation patients, a potential harbinger of stroke. Leveraging computed tomography angiography (CTA) images, radiologists interpret the left atrium (LA) and LAA geometries to stratify stroke risk. Nevertheless, accurate LA segmentation remains a time-consuming task with high inter-observer variability. Binary masks of the LA and their corresponding CTA images were used to train and test a 3D U-Net to automate LA segmentation. One model was trained using the entire unified-image-volume while a second model was trained on regional patch-volumes which were run for inference and then assimilated back into the full volume. The unified-image-volume U-Net achieved median DSCs of 0.92 and 0.88 for the train and test sets, respectively; the patch-volume U-Net achieved median DSCs of 0.90 and 0.89 for the train and test sets, respectively. This indicates that the unified-image-volume and patch-volume U-Net models captured up to 88 and 89% of the LA/LAA boundary's regional complexity, respectively. Additionally, the results indicate that the LA/LAA were fully captured in most of the predicted segmentations. By automating the segmentation process, our deep learning model can expedite LA/LAA shape, informing stratification of stroke risk.

This study proposes a new diagnostic tool for automatically extracting discriminative features and detecting temporomandibular joint disc displacement (TMJDD) accurately with artificial intelligence. We analyzed the structural magnetic resonance imaging (MRI) images of 52 patients with TMJDD and 32 healthy controls. The data were split into training and test sets, and only the training sets were used for model construction. U-net was trained with 100 sagittal MRI images of the TMJ to detect the joint cavity between the temporal bone and the mandibular condyle, which was used as the region of interest, and classify the images into binary categories using four convolutional neural networks: InceptionResNetV2, InceptionV3, DenseNet169, and VGG16. The best models were InceptionV3 and DenseNet169; the results of InceptionV3 for recall, precision, accuracy, and F1 score were 1, 0.81, 0.85, and 0.9, respectively, and the corresponding results of DenseNet169 were 0.92, 0.86, 0.85, and 0.89, respectively. Automated detection of TMJDD from sagittal MRI images is a promising technique that involves using deep learning neural networks. It can be used to support clinicians in diagnosing patients as having TMJDD.

Cerebral vascular autoregulation is impaired following resuscitation from cardiac arrest (CA), and its quantification may allow assessing CA-induced brain injury. However, hyperemia occurring immediately post-resuscitation limits the application of most metrics that quantify autoregulation. Therefore, to characterize autoregulation during this critical period, we developed three novel metrics based on how the cerebrovascular resistance (CVR) covaries with changes in cerebral perfusion pressure (CPP): (i) θCVR, which quantifies the CVR vs CPP gradient, (ii) a CVR-based transfer function analysis, and (iii) CVRx, the correlation coefficient between CPP and CVR. We tested these metrics in a model of asphyxia induced CA and resuscitation using seven adult male Wistar rats. Mean arterial pressure (MAP) and cortical blood flow recorded for 30 min post-resuscitation via arterial cannulation and laser speckle contrast imaging, were used as surrogates of CPP and cerebral blood flow (CBF), while CVR was computed as the CPP/CBF ratio. Using our metrics, we found that the status of cerebral vascular autoregulation altered substantially during hyperemia, with changes spread throughout the 0-0.05 Hz frequency band. Our metrics push the boundary of how soon autoregulation can be assessed, and if validated against outcome markers, may help develop a reliable metric of brain injury post-resuscitation.

Single ventricle physiology (SVP) is used to describe any congenital heart lesion that is unable to support independent pulmonary and systemic circulations. Current treatment strategies rely on a series of palliation surgeries that culminate in the Fontan physiology, which relies on the single functioning ventricle to provide systemic circulation while passively routing venous return through the pulmonary circulation. Despite significant reductions in early mortality, the presence of atrioventricular valve (AVV) regurgitation is a key predictor of heart failure in these patients. We sought to evaluate the biomechanical changes associated with the AVV in SVP physiologies. Left and right ventricles were sutured onto patient-derived 3D-printed mounts and mounted into an ex vivo systemic heart simulator capable of reproducing Norwood, Glenn, Fontan and Late Fontan physiologies. We found that the tricuspid anterior leaflet experienced elevated maximum force, average force, and maximum yank compared to the posterior and septal leaflets. Between physiologies, maximum yank was greatest in the Norwood physiology relative to the Glenn, Fontan, and Late Fontan physiologies. These contrasting trends suggest that long- and short-term mechanics of AVV failure in single ventricle differ and that AVV interventions should account for asymmetries in force profiles between leaflets and physiologies.

Impaired cardiac filling in response to increased passive myocardial stiffness contributes to the pathophysiology of heart failure. By leveraging cardiac MRI data and ventricular pressure measurements, we can estimate in vivo passive myocardial stiffness using personalized inverse finite element models. While it is well-known that this approach is subject to uncertainties, only few studies quantify the accuracy of these stiffness estimates. This lack of validation is, at least in part, due to the absence of ground truth in vivo passive myocardial stiffness values. Here, using 3D printing, we created soft, homogenous, isotropic, hyperelastic heart phantoms of varying geometry and stiffness and simulate diastolic filling by incorporating the phantoms into an MRI-compatible left ventricular inflation system. We estimate phantom stiffness from MRI and pressure data using inverse finite element analyses based on a Neo-Hookean model. We demonstrate that our identified softest and stiffest values of 215.7 and 512.3 kPa agree well with the ground truth of 226.2 and 526.4 kPa. Overall, our estimated stiffnesses revealed a good agreement with the ground truth ([Formula: see text] error) across all models. Our results suggest that MRI-driven computational constitutive modeling can accurately estimate synthetic heart material stiffnesses in the range of 200-500 kPa.

Osteochondral allograft transplantations are typically used to treat focal articular cartilage injuries where the damaged cartilage is replaced with fresh cadaveric donor grafts. Despite the notable success rate of this procedure, it is limited by fresh donor tissue availability which can only be stored for approximately 28 days after harvest. Vitrification, a form of cryopreservation, can extend the storage time of cartilage. Although it has shown to preserve chondrocyte viability, its effect on the mechanical properties of the tissue has not been thoroughly investigated. Therefore, in this study, the mechanical properties of fresh, frozen, and vitrified articular cartilage were evaluated through unconfined compression testing. Results showed that the peak modulus, equilibrium modulus, and relaxation time constants of the vitrified and control samples (tested one day after harvest) were similar and higher than the fresh (tested 21 days after harvest) and frozen samples. This demonstrated that vitrification does not adversely affect the mechanical properties of cartilage and can be used as an alternative to fresh allografts which are limited by storage time. The fresh samples also had inferior mechanical properties compared to the control samples suggesting that vitrified allografts could potentially improve clinical outcomes in addition to increasing donor tissue availability.

This manuscript presents new experimental methods for testing the ex vivo tensile properties of the uterosacral ligaments (USLs) in rats. The USL specimens ([Formula: see text]) were carefully dissected to preserve their anatomical attachments, and they were loaded along their main in vivo loading direction (MD) using a custom-built uniaxial tensile testing device. During loading, strain maps in both the MD and the perpendicular direction (PD) were collected using the digital image correlation technique. The mean (± S.E.M.) maximum load and displacement at the maximum load were [Formula: see text] N and [Formula: see text] mm, respectively. The USLs were found to be highly heterogeneous structures, with some specimens experiencing strains in the MD that were lower than [Formula: see text] and others reaching strains that were up to [Formula: see text] in the intermediate region. At 0.5 kPa stress, a value reached by all the specimens, the mean strain in the MD was [Formula: see text] while at 5 kPa stress, a value achieved only by 9 out of the 21 specimens, the mean strain increased to [Formula: see text]. Under uniaxial loading, the specimens also elongated in the PD, with strains that were one order of magnitude lower than the strains in the MD; at the 0.5 kPa stress, the mean strain in the PD was recorded to be [Formula: see text] and, at the 5 kPa stress, the strain in the PD was [Formula: see text]. The directions of maximum principal strains remained almost unchanged with the increase in stress, indicating that little microstructural re-organization occurred due to uniaxial loading. This study serves as a springboard for future investigations on the supportive function of the USLs in the rat model by offering guidelines on testing methods that capture their complex mechanical behavior.

Scholars increasingly rely on new artificial intelligence models for convenience and simple access to necessities due to the rapid evolution of scientific literature and technology. The invention of ChatGPT by OpenAI stands out as a key example of how significant advances in large language model technology have recently changed the field of artificial intelligence (AI). Since ChatGPT's development, it has been tested by multiple sectors on various topics to see how well it functions in a natural and conversational mode. The crucial question is how much ChatGPT can influence global health policy analysis. In this article, the researcher briefly explains ChatGPT's potential and the difficulties that users, such as researchers or policymakers, may continue to face.

Near-infrared spectroscopy (NIRS)-based peripheral perfusion, or microcirculation, can be used to assess the severity of peripheral vascular dysfunction. A low-cost, portable non-contact near-infrared optical scanner (NIROS) was developed for spatio-temporal mapping of tissue oxygenation and perfusion in tissues. In vivo validation studies were carried out on control subjects (n = 3) to assess the ability of NIROS to measure real-time oxygenation changes in response to an occlusion paradigm on the dorsum of the hand. NIROS captured real-time tissue oxygenation changes with 95% correlation when compared to a commercial device. A feasibility peripheral imaging study was performed in a mouse model (n = 5) of chronic kidney disease (CKD) induced vascular calcification to assess differences in microcirculatory peripheral tissue oxygenation. The tissue oxygenation (in terms of oxy-, deoxy-, and total hemoglobin changes) due to the occlusion paradigm was distinctly different prior to (week-6) and after the onset of vascular calcification (week-12) in the murine tails. Future work will involve extensive studies to correlate these microcirculatory tissue oxygenation changes in the peripheral tail to the vascular calcification in the heart.

The current study aims to demonstrate the feasibility of a novel balloon-integrated optical catheter (BIOC) to achieve endoscopic laser application for circumferential coagulation of a tubular tissue structure. Both optical and thermal numerical simulations were developed to predict the propagation of laser light and a spatio-temporal distribution of temperature in tissue. Ex vivo esophagus tissue was tested with 980 nm laser light at 30 W for 90 s for quantitative evaluations. In vivo porcine models were used to validate the performance of BIOC for circumferential and endoscopic laser coagulation of esophagus in terms of acute tissue responses post-irradiation. Optical simulations confirmed that a diffusing applicator was able to generate a circumferential light distribution in a tubular tissue structure. Both numerical and experimental results presented that the maximum temperature elevation occurred at 3-5 mm (muscle layer) below the mucosa surface after 90 s irradiation. In vivo tests confirmed the circumferential delivery of laser light to a deep muscle layer as well as no evidence of thermal damage to the esophageal mucosa. The proposed BIOC can be a feasible optical device to provide circumferential laser irradiation as well as endoscopic coagulation of tubular esophagus tissue for clinical applications.

Anticipating changes to vehicle interiors with future automated driving systems, the automobile industry recently has focused attention on crash response in novel postures with increased seatback recline. Prior research found that this posture may result in greater risk of lumbar spine injury in the event of a frontal crash. This study developed a lumbar spine injury risk function (IRF) that estimated injury risk as a function of simultaneously applied compression force and flexion moment. Force and moment failure data from 40 compression-flexion tests were utilized in a Weibull survival model, including appropriate data censoring. A mechanics-based injury metric was formulated, where lumbar spine compression force and flexion moment were normalized by specimen geometry. Subject age was incorporated as a covariate to further improve model fit. A weighting factor was included to adjust the influence of force and moment, and parameter optimization yielded a value of 0.11. Thus, the normalized compression force component had a greater effect on injury risk than the normalized flexion moment component. Additionally, as force was nominally increased, less moment was required to produce injury for a given age and specimen geometry. The resulting IRF may be utilized to improve occupant safety in the future.

The biomechanics and efficacy of personal protective equipment in mitigating injuries from blast overpressure remain unclear. The objectives of this study were to define intrathoracic pressures in response to blast wave (BW) exposure and biomechanically evaluate a soft-armor vest (SA) at diminishing these perturbations. Male Sprague-Dawley rats were instrumented with pressure sensors in the thorax and were exposed laterally to multiple exposures ranging from 33 to 108 kPa BW with SA and without SA. There were significant increases in rise time, peak negative pressure, and negative impulse in the thoracic cavity compared to the BW. Esophageal measurements were increased to a greater extent when compared to the carotid and the BW for all parameters (except positive impulse, which decreased). SA minimally altered the pressure parameters and energy content. This study establishes the relationship of external blast flow conditions and intra-body biomechanical responses in the thoracic cavity of rodents with and without SA.

Microvascular Obstruction (MVO) is a common consequence of acute myocardial infarction. MVO is underdiagnosed and treatment is often nonspecific and ineffective. A multi-scale in-vitro benchtop model was established to investigate drug perfusion in MVO affected microcirculation. The central element of the benchtop model was a fluidic microchip containing channels with diameters between [Formula: see text] and 50 μm representing [Formula: see text] of the microvascular tree fed by the left anterior descending artery (LAD). The outlets of the chip could be closed to mimic MVO. Two methods for intracoronary infusion of pharmacologic agents (simulated by dye) to regions with MVO were investigated using an occlusion-infusion catheter. The first case was a simple, bolus-like infusion into the LAD, whereas the second case consisted of infusion with concomitant proximal occlusion of the LAD phantom with a balloon. Results show that local dye concentration maxima in the chip with MVO were 2.2-3.2 times higher for the case with proximal balloon occlusion than for the conventional infusion method. The cumulated dose could be raised by a factor 4.6-5.2. These results suggest that drug infusion by catheter is more effective if the blood supply to the treated vascular bed is temporarily blocked by a balloon catheter.

Pedestrians who use wheelchairs (seated pedestrians) report higher mortality rates than standing pedestrians in vehicle-to-pedestrian collisions but the cause of this mortality is poorly understood. This study investigated the cause of seated pedestrian serious injuries (AIS 3+) and the effect of various pre-collision variables using finite element (FE) simulations. An ultralight manual wheelchair model was developed and tested to meet ISO standards. The GHBMC 50th percentile male simplified occupant model and EuroNCAP family car (FCR) and sports utility vehicle (SUV) were used to simulate vehicle collisions. A full factorial design of experiments (n = 54) was run to explore the effect of pedestrian position relative to the vehicle bumper, pedestrian arm posture, and pedestrian orientation angle relative to the vehicle. The largest average injury risks were at the head (FCR: 0.48 SUV: 0.79) and brain (FCR: 0.42 SUV: 0.50). The abdomen (FCR: 0.20 SUV: 0.21), neck (FCR: 0.08 SUV: 0.14), and pelvis (FCR: 0.02 SUV: 0.02) reported smaller risks. 50/54 impacts reported no thorax injury risk, but 3 SUV impacts reported risks ≥ 0.99. Arm (gait) posture and pedestrian orientation angle had larger effects on most injury risks. The most dangerous arm posture examined was when the hand was off the wheelchair handrail after wheel propulsion and the two more dangerous orientations were when the pedestrian faced 90° and 110° away from the vehicle. Pedestrian position relative to the vehicle bumper played little role in injury outcomes. The findings of this study may inform future seated pedestrian safety testing procedures to narrow down the most concerning impact scenarios and design impact tests around them.

Gait patterns are critical to health monitoring, gait impairment assessment, and wearable device control. Unrhythmic gait pattern detection under community-based conditions is a new frontier in this area. The present paper describes a high-accuracy gait phase estimation and prediction algorithm built on a two-stage artificial neural network. This work targets to develop an algorithm that can estimate and predict the gait cycle in real time using a portable controller with only two IMU sensors (one on each thigh) in the community setting. Our algorithm can detect the gait phase in unrhythmic conditions during walking, stair ascending, and stair descending, and classify these activities with standing. Moreover, our algorithm is able to predict both future intra- and inter-stride gait phases, offering a potential means to improve wearable device controller performance. The proposed data-driven algorithm is based on a dataset consisting of 5 able-bodied subjects and validated on 3 different able-bodied subjects. Under unrhythmic activity situations, validation shows that the algorithm can accurately identify multiple activities with 99.55% accuracy, and estimate ([Formula: see text]: 6.3%) and predict 200-ms-ahead ([Formula: see text]: 8.6%) the gait phase percentage in real time, which are on average 57.7 and 54.0% smaller than the error from the event-based method in the same conditions. This study showcases a solution to estimate and predict gait status for multiple unrhythmic activities, which may be deployed to controllers for wearable robots or health monitoring devices.

Endovascular thrombectomy procedures are significantly influenced by the mechanical response of thrombi to the multi-axial loading imposed during retrieval. Compression tests are commonly used to determine compressive ex vivo thrombus and clot analogue stiffness. However, there is a shortage of data in tension. This study compares the tensile and compressive response of clot analogues made from the blood of healthy human donors in a range of compositions. Citrated whole blood was collected from six healthy human donors. Contracted and non-contracted fibrin clots, whole blood clots and clots reconstructed with a range of red blood cell (RBC) volumetric concentrations (5-80%) were prepared under static conditions. Both uniaxial tension and unconfined compression tests were performed using custom-built setups. Approximately linear nominal stress-strain profiles were found under tension, while strong strain-stiffening profiles were observed under compression. Low- and high-strain stiffness values were acquired by applying a linear fit to the initial and final 10% of the nominal stress-strain curves. Tensile stiffness values were approximately 15 times higher than low-strain compressive stiffness and 40 times lower than high-strain compressive stiffness values. Tensile stiffness decreased with an increasing RBC volume in the blood mixture. In contrast, high-strain compressive stiffness values increased from 0 to 10%, followed by a decrease from 20 to 80% RBC volumes. Furthermore, inter-donor differences were observed with up to 50% variation in the stiffness of whole blood clot analogues prepared in the same manner between healthy human donors.

The emergence of artificial intelligence (AI) offers unprecedented opportunities for joint arthroplasty surgery. Notably, on 14th March, 2023, the OpenAI company officially launched its latest version GPT-4, which once again become the focus of discussion on social media. Although more than 200 articles have reported the potential role of ChatGPT/GPT-4 in various areas, there are no studies that discussed the potential of GPT-4 as an AI-powered virtual assistant for surgeons specialized in joint arthroplasty. In this study, we summarized the five major roles of GPT-4 including scientific research, disease diagnosis, treatment options, preoperative planning, intraoperative support, and postoperative rehabilitation for arthroplasty doctors. Of note, in parallel to enjoy AI dividend, it is also necessary to pay attention to protect the data from misuse with ethical considerations in place.

Acute respiratory distress syndrome (ARDS) has a high mortality rate that is due in part to ventilator-induced lung injury (VILI). Nevertheless, the majority of patients eventually recover, which means that their innate reparative capacities eventually prevail. Since there are currently no medical therapies for ARDS, minimizing its mortality thus amounts to achieving an optimal balance between spontaneous tissue repair versus the generation of VILI. In order to understand this balance better, we developed a mathematical model of the onset and recovery of VILI that incorporates two hypotheses: (1) a novel multi-hit hypothesis of epithelial barrier failure, and (2) a previously articulated rich-get-richer hypothesis of the interaction between atelectrauma and volutrauma. Together, these concepts explain why VILI appears in a normal lung only after an initial latent period of injurious mechanical ventilation. In addition, they provide a mechanistic explanation for the observed synergy between atelectrauma and volutrauma. The model recapitulates the key features of previously published in vitro measurements of barrier function in an epithelial monolayer and in vivo measurements of lung function in mice subjected to injurious mechanical ventilation. This provides a framework for understanding the dynamic balance between factors responsible for the generation of and recovery from VILI.

In this study, we analyzed the clinical factors and mechanical parameters for predicting orthodontic mini-implant (OMI) failure in the mandible, which has different properties from the maxilla. A patient-specific finite element analysis was applied to 32 OMIs (6 failures and 26 successes) implanted between the mandibular second premolars and first molars used for anchorage. The peak stress and strain parameters were calculated for each sample. A logistic regression of the failure (vs. success) of OMIs on the mechanical parameters in the models was conducted. In addition, the influence of clinical factors on the mechanical parameters considered to be related to OMI failure was examined by a regression analysis. The mechanical parameter which best predicts OMI failure in the mandible was found to be a minimum principal strain of between 0.5 to 1.0 mm from the OMI surface (R2 = 0.8033). The results indicate the patient's bone density, distance between the OMIs and adjacent root, and vertical implantation angle of the OMIs are potential clinical predictors of OMI failure in the mandible.

The implementation of technology in healthcare has revolutionized patient-centered decision making by providing contextualized information about a patient's healthcare journey, leading to increased efficiency (Keyworth et al. in BMC Med Inform Decis Mak 18:93, 2018, https://doi.org/10.1186/s12911-018-0661-3 ). Artificial intelligence has been integrated within Electronic Health Records (EHR) to prompt screenings or diagnostic tests based on a patient's holistic health profile. While larger hospitals have already widely adopted these technologies, free clinics hold lower utilization of these advanced capability EHRs. The patient population at a free clinic faces a multitude of factors that limits their access to comprehensive care, thus requiring necessary efforts and measures to close the gap in healthcare disparities. Emerging Artificial Intelligence (AI) technology, such as OpenAI's ChatGPT, GPT-4, and other large language models (LLMs) have remarkable potential to improve patient care outcomes, promote health equity, and enhance comprehensive and holistic care in resource-limited settings. This paper aims to identify areas in which integrating these LLM AI advancements into free clinics operations can optimize and streamline healthcare delivery to underserved patient populations. This paper also identifies areas of improvements in GPT that are necessary to deliver those services.

Inverse bone (re)modeling (IBR) can infer physiological loading conditions from the bone microstructure. IBR scales unit loads, imposed on finite element (FE) models of a bone, such that the trabecular microstructure is homogeneously loaded and the difference to a target stimulus is minimized. Micro-FE (µFE) analyses are typically used to model the microstructure, but computationally more efficient, homogenized FE (hFE) models, where the microstructure is replaced by an equivalent continuum, could be used instead. However, also the target stimulus has to be translated from the tissue to the continuum level. In this study, a new continuum-level target stimulus relating relative bone density and strain energy density is proposed. It was applied using different types of hFE models to predict the physiological loading of 21 distal radii sections, which was subsequently compared to µFE-based IBR. The hFE models were able to correctly identify the dominant load direction and showed a high correlation of the predicted forces, but mean magnitude errors ranged from - 14.7 to 26.6% even for the best models. While µFE-based IBR can still be regarded as a gold standard, hFE-based IBR enables faster predictions, the usage of more sophisticated boundary conditions, and the usage of clinical images.

The asymmetries study between both legs of the forces applied to the pedals in cycling is important because they may affect the performance of the cyclist or prevent the occurrence of injuries. Studies focused on analysing asymmetries in forces tend to consider only the effective force, disregarding the three-dimensional nature of the force. Furthermore, these studies do not analyse the possible physical or neurological causes that may have led to the appearance of the asymmetries. This paper presents a methodology to carry out three-dimensional analysis of the asymmetries of the forces applied in both pedals and discriminate the possible sources of these asymmetries. Seven participants, amateurs and without pathologies, were analysed. Two commercial pedals were instrumented to measure the three components of the force applied to each pedal. The Normalized Symmetry Index (NSI) and the Cross Correlation Coefficient (CCC) were used for the asymmetries analysis. Results showed that both indexes need to be used in conjunction to analyse the causes of asymmetry in the pedal forces from a 3D perspective along the pedal cycle. The NSI is an index that makes it possible to evaluate asymmetry by considering only the value of the force applied by each leg at each instant. The CCC makes it possible to evaluate whether the temporal evolutions of the forces applied by each leg are similar. Preliminary results suggest that the proposed methodology is effective for analysing asymmetries in the forces in a pedalling cycle from a three-dimensional point of view. Forces in the sagittal plane showed a high level of symmetry. The lateral-medial force presented the highest level of asymmetry due to the difference in the magnitudes of the applied forces by both legs and the existing time shift between the two force patterns. The results of this work will allow for more complete and accurate three-dimensional dynamic analyses of the lower body during pedalling.

We investigated the potential correlation between the fluid shear stress and the proliferation of bone prostate cancer cells on the surface of nanoclay-based scaffolds in a perfusion bioreactor. Human mesenchymal stem cells (hMSCs) were seeded on the scaffolds to initiate bone growth. After 23 days, prostate cancer cells (MDAPCa2b) were cultured on top of the osteogenically differentiated hMSCs. The scaffolds were separated into two groups subjected to two distinct conditions: (i) static (no flow); and (ii) dynamic (with flow) conditions to recapitulate bone metastasis of prostate cancer. Based on measured data, Computational Fluid Dynamics (CFD) models were constructed to determine the velocity and shear stress distributions on the scaffold surface. Our experimental results show distinct differences in the growth pattern of hMSCs and MDAPCa2b cells between the static and dynamic conditions. Our computational results further suggest that the dynamic flow leads to drastic change in cell morphology and tumorous distribution. Our work points to a strong correlation between tumor growth and local interstitial flows in bones.

Articular cartilage defects and degenerative diseases are pathological conditions that cause pain and the progressive loss of joint functionalities. The most severe cases are treated through partial or complete joint replacement with prostheses, even if the interest in cartilage regeneration and re-growth methods is steadily increasing. These methods consist of the targeted deposition of biomaterials. Only a few tools have been developed so far for performing these procedures in a minimally invasive way. This work presents an innovative device for the direct deposition of multiple biomaterials in an arthroscopic scenario. The tool is easily handleable and allows the extrusion of three different materials simultaneously. It is also equipped with a flexible tip to reach remote areas of the damaged cartilage. Three channels are arranged coaxially and a spring-based dip-coating approach allows the fabrication and assembly of a bendable polymeric tip. Experimental tests were performed to characterize the tip, showing the ability to bend it up to 90° (using a force of ~ 1.5 N) and to extrude three coaxial biomaterials at the same time with both tip straight and tip fully bent. Rheometric analysis and fluid-dynamic computational simulations were performed to analyze the fluids' behavior; the maximum shear stresses were observed in correspondence to the distal tip and the channel convergence chamber, but with values up to ~ 1.2 kPa, compatible with a safe extrusion of biomaterials, even laden with cells. The cells viability was assessed after the extrusion with Live/Dead assay, confirming the safety of the extrusion procedures. Finally, the tool was tested arthroscopically in a cadaveric knee, demonstrating its ability to deliver the biomaterial in different areas, even ones that are typically hard-to-reach with traditional tools.

Subcutaneous injection, which is a preferred delivery method for many drugs, causes deformation, damage, and fracture of the subcutaneous tissue. Yet, experimental data and constitutive modeling of these dissipation mechanisms in subcutaneous tissue remain limited. Here we show that subcutaneous tissue from the belly and breast anatomical regions in the swine show nonlinear stress-strain response with the characteristic J-shaped behavior of collagenous tissue. Additionally, subcutaneous tissue experiences damage, defined as a decrease in the strain energy capacity, as a function of the previously experienced maximum deformation. The elastic and damage response of the tissue are accurately described by a microstructure-driven constitutive model that relies on the convolution of a neo-Hookean material of individual fibers with a fiber orientation distribution and a fiber recruitment distribution. The model fit revealed that subcutaneous tissue can be treated as initially isotropic, and that changes in the fiber recruitment distribution with loading are enough to explain the dissipation of energy due to damage. When tested until failure, subcutaneous tissue that has undergone damage fails at the same peak stress as virgin samples, but at a much larger stretch, overall increasing the tissue toughness. Together with a finite element implementation, these data and constitutive model may enable improved drug delivery strategies and other applications for which subcutaneous tissue biomechanics are relevant.

Wearable assistive technology for the lower extremities has shown great promise towards improving gait function in people with neuromuscular injuries. But common secondary impairments, such as hypersensitive stretch reflexes or hyperreflexia, have been often neglected. Incorporation of biomechanics into the control loop could improve individualization and avoid hyperreflexia. However, adding hyperreflexia prediction to the control loop would require expensive or complex measurement of muscle fiber characteristics. In this study, we explore a clinically accessible biomechanical predictor set that can accurately predict rectus femoris (RF) reaction after knee flexion assistance in pre-swing by a powered orthosis. We examined a total of 14 gait parameters based on gait kinematic, kinetic, and simulated muscle-tendon states from 8 post-stroke individuals with Stiff-Knee gait (SKG) wearing a knee exoskeleton robot. We independently performed both parametric and non-parametric variable selection approaches using machine learning regression techniques. Both models revealed the same four kinematic variables relevant to knee and hip joint motions were sufficient to effectively predict RF hyperreflexia. These results suggest that control of knee and hip kinematics may be a more practical method of incorporating quadriceps hyperreflexia into the exoskeleton control loop than the more complex acquisition of muscle fiber properties.

Type-B aortic dissection (TBAD) is a disease in which a tear develops in the intimal layer of the descending aorta forming a true lumen and false lumen (FL). Because disease outcomes are thought to be influenced by haemodynamic quantities such as pressure and wall shear stress (WSS), their analysis via numerical simulations may provide valuable clinical insights. Major aortic branches are routinely included in simulations but minor branches are virtually always neglected, despite being implicated in TBAD progression and the development of complications. As minor branches are estimated to carry about 7-21% of cardiac output, neglecting them may affect simulation accuracy. We present the first simulation of TBAD with all pairs of intercostal, subcostal and lumbar arteries, using 4D-flow MRI (4DMR) to inform patient-specific boundary conditions. Compared to an equivalent case without minor branches, their inclusion improved agreement with 4DMR velocities, reduced time-averaged WSS (TAWSS) and transmural pressure and elevated oscillatory shear in regions where FL dilatation and calcification were observed in vivo. Minor branch inclusion resulted in differences of 60-75% in these metrics of potential clinical relevance, indicating a need to account for minor branch flow loss if simulation accuracy is sought.

Mesenchymal stromal cells (MSCs) are under investigation for wound healing and tissue regeneration due to their potent secretome. Compared to monodisperse cells, MSC spheroids exhibit increased cell survival and enhanced secretion of endogenous factors such as vascular endothelial growth factor (VEGF) and prostaglandin E2 (PGE2), two key factors in wound repair. We previously upregulated the proangiogenic potential of homotypic MSC spheroids by manipulating microenvironmental culture conditions. However, this approach depends on the responsiveness of host endothelial cells (ECs)-a limitation when attempting to restore large tissue deficits and for patients with chronic wounds in which ECs are dysfunctional and unresponsive. To address this challenge, we used a Design of Experiments (DOE) approach to engineer functionally distinct MSC spheroids that maximize VEGF production (VEGFMAX) or PGE2 production (PGE2,MAX) while incorporating ECs that could serve as the basic building blocks for vessel formation. VEGFMAX produced 22.7-fold more VEGF with enhanced endothelial cell migration compared to PGE2,MAX, while PGE2,MAX produced 16.7-fold more PGE2 with accelerated keratinocyte migration compared to VEGFMAX. When encapsulated together in engineered protease-degradable hydrogels as a model of cell delivery, VEGFMAX and PGE2,MAX spheroids exhibited robust spreading into the biomaterial and enhanced metabolic activity. The distinct bioactivities of these MSC spheroids demonstrate the highly tunable nature of spheroids and provide a new approach to leverage the therapeutic potential of cell-based therapies.

Brain and spinal cord injuries have devastating consequences on quality of life but are challenging to assess experimentally due to the traumatic nature of such injuries. Finite element human body models (HBM) have been developed to investigate injury but are limited by a lack of biofidelic spinal cord implementation. In many HBM, brain models terminate with a fixed boundary condition at the brain stem. The goals of this study were to implement a comprehensive representation of the spinal cord into a contemporary head and neck HBM, and quantify the effect of the spinal cord on brain deformation during simulated impacts. Spinal cord tissue geometries were developed, based on 3D medical imaging and literature data, meshed, and implemented into the GHBMC 50th percentile male model. The model was evaluated in frontal, lateral, rear, and oblique impact conditions, and the resulting maximum principal strains in the brain tissue were compared, with and without the spinal cord. A new cumulative strain curve metric was proposed to quantify brain strain distribution. Presence of the spinal cord increased brain tissue strains in all simulated cases, owing to a more compliant boundary condition, highlighting the importance of the spinal cord to assess brain response during impact.

Neuromusculoskeletal models can be used to evaluate aberrant muscle function in cerebral palsy (CP), for example by estimating muscle and joint contact forces during gait. However, to be accurate, models should include representative musculotendon parameters. We aimed to estimate personalised parameters that capture the mechanical behaviour of the plantarflexors in children with CP and typically developing (TD) children. Ankle angle (using motion capture), torque (using a load-cell), and medial gastrocnemius fascicle lengths (using ultrasound) were measured during slow passive ankle dorsiflexion rotation for thirteen children with spastic CP and thirteen TD children. Per subject, the measured rotation was input to a scaled OpenSim model to simulate the torque and fascicle length output. Musculotendon model parameters were personalised by the best match between simulated and experimental torque-angle and fascicle length-angle curves according to a least-squares fit. Personalised tendon slack lengths were significantly longer and optimal fibre lengths significantly shorter in CP than model defaults and than in TD. Personalised tendon compliance was substantially higher in both groups compared to the model default. The presented method to personalise musculotendon parameters will likely yield more accurate simulations of subject-specific muscle mechanics, to help us understand the effects of altered musculotendon properties in CP.

In this pilot study, we characterize and evaluate 3D-printed swabs for the collection of nasopharyngeal and oropharyngeal secretion samples for the SARS-CoV-2 detection. Swabs are made with the fused deposition modeling technique using the biopolymer polylactic acid (PLA) which is a medical-grade, biodegradable and low-cost material. We evaluated six swabs with mechanical tests in a laboratory and in an Adult Human Simulator performed by healthcare professionals. We proved the adequacy of the PLA swab to be used in the gold standard reverse transcriptase-polymerase chain reaction (qRT-PCR) for viral RNA detection. Then, we did in vitro validation for cell collection using the 3D-printed swabs and RNA extraction for samples from 10 healthy volunteers. The 3D-printed swabs showed good flexibility and maneuverability for sampling and at the same time robustness to pass into the posterior nasopharynx. The PLA did not interfere with the RNA extraction process and qRT-PCR test. When we evaluated the expression of the reference gene (RNase P) used in the SARS-CoV-2 detection, the 3D-printed swabs showed good reproducibility in the threshold cycle values (Ct = 23.5, range 19-26) that is comparable to control swabs (Ct = 24.7, range 20.8-32.6) with p value = 0.47. The 3D-printed swabs demonstrated to be a reliable, and an economical alternative for mass use in the detection of SARS-CoV-2.

Four-dimensional (4D) flow magnetic resonance imaging (MRI) is a leading-edge imaging technique and has numerous medicinal applications. In vitro 4D flow MRI can offer some advantages over in vivo ones, especially in accurately controlling flow rate (gold standard), removing patient and user-specific variations, and minimizing animal testing. Here, a complete testing method and a respiratory-motion-simulating platform are proposed for in vitro validation of 4D flow MRI. A silicon phantom based on the hepatic arteries of a living pig is made. Under the free-breathing, a human volunteer's liver motion (inferior-superior direction) is tracked using a pencil-beam MRI navigator and is extracted and converted into velocity-distance pairs to program the respiratory-motion-simulating platform. With the magnitude displacement of about 1.3 cm, the difference between the motions obtained from the volunteer and our platform is ≤ 1 mm which is within the positioning error of the MRI navigator. The influence of the platform on the MRI signal-to-noise ratio can be eliminated even if the actuator is placed in the MRI room. The 4D flow measurement errors are respectively 0.4% (stationary phantom), 9.4% (gating window = 3 mm), 27.3% (gating window = 4 mm) and 33.1% (gating window = 7 mm). The vessel resolutions decreased with the increase of the gating window. The low-cost simulation system, assembled from commercially available components, is easy to be duplicated.

As artificial intelligence (AI) permeates various fields, ChatGPT emerges as a contentious force in biomedical engineering, stirring both excitement and concern. This letter explores the disruptive potential and controversial implications of ChatGPT on research, collaboration, and the future of the field. By presenting thought-provoking questions and confronting divisive issues, we aim to spark a lively debate on the responsible integration of AI technology in biomedical engineering while safeguarding the essence of human expertise.

There is a growing number of protein drugs, yet their limited oral bioavailability requires that patients receive frequent, high dose injections. In situ forming implants (ISFIs) for controlled release of biotherapeutics have the potential to greatly reduce the injection frequency and improve patient compliance. However, protein release from ISFIs is a challenge due to their proclivity for instability. Specifically, factors such as the acidic microclimate within ISFIs can lead to protein aggregation and denaturation. Basic salts have been shown in PLGA microparticle and microcylinder formulations to significantly reduce protein instability by neutralizing this acidic environment. The overall objective of the study was to demonstrate that basic salts can be used with an ISFI system to neutralize the implant acidification. To this end, the basic salts MgCO3 and Mg(OH)2 were added to a protein-releasing ISFI and the effect on drug release, pH, implant swelling, implant diffusivity, and implant erosion were evaluated. Either salt added at 3 wt% neutralized the acidic environment surrounding the implants, keeping the pH at 6.64 ± 0.03 (MgCO3) and 6.46 ± 0.11 (Mg(OH)2) after 28 day compared to 3.72 ± 0.05 with no salts added. The salts initially increased solution uptake into the implants but delayed implant degradation and erosion. The 3 wt% Mg(OH)2 formulation also showed slightly improved drug release with a lower burst and increased slope. We showed that salt additives can be an effective way to modulate the pH in the ISFI environment, which can improve protein stability and ultimately improve the capacity of ISFIs for delivering pH-sensitive biomolecules. Such a platform represents a low-cost method of improving overall patient compliance and reducing the overall healthcare burden.

Emerging treatments for tricuspid valve (TV) regurgitation require realistic TV pathological models for preclinical testing. The aim of this work was to investigate structural features of fresh and defrosted porcine right-heart samples as models of mild and severe functional tricuspid regurgitation (FTR) condition in ex-vivo pulsatile flow platform. Ten fresh hearts were tested ex-vivo under steady and pulsatile flow in typical right-heart loading conditions. Hemodynamics and 3D echocardiographic imaging of TV and right ventricle (RV) were acquired. Hearts were then kept frozen for 14 days, defrosted, and tested again with the same protocol. Morphometric parameters of TV and RV were derived from 3D reconstructions based on echo data. Fresh samples showed a slightly dilated TV morphology, with coaptation gaps among the leaflets. Sample freezing induced worsening of TV insufficiency, with significant (p < 0.05) increases in annulus size (annulus area and perimeter 7.7-3.1% respectively) and dilation of RV (9.5%), which led to an increase in tenting volume (123.7%). These morphologic alterations reflected into a significant increment of regurgitation fraction (27%). Together, such results suggest that fresh porcine heart samples may be a reliable ex-vivo model of mild FTR condition, which can be enhanced through freezing/thawing treatment to model a severe pathological condition.

Instrumented mouthguards have been used to detect head accelerations and record kinematic data in numerous sports. Each recording requires validation through time-consuming video verification. Classification algorithms have been posed to automatically categorise head acceleration events and spurious events. However, classification algorithms must be designed and/or validated for each combination of sport, sex and mouthguard system. This study provides the first algorithm to classify head acceleration data from exclusively female rugby union players. Mouthguards instrumented with kinematic sensors were given to 25 participants for six competitive rugby union matches in an inter-university league. Across all instrumented players, 214 impacts were recorded from 460 match-minutes. Matches were video recorded to enable retrospective labelling of genuine and spurious events. Four machine learning algorithms were trained on five matches to predict these labels, then tested on the sixth match. Of the four classifiers, the support vector machine achieved the best results, with area under the receiver operator curve (AUROC) and area under the precision recall curve (AUPRC) scores of 0.92 and 0.85 respectively, on the test data. These findings represent an important development for head impact telemetry in female sport, contributing to the safer participation and improving the reliability of head impact data collection within female contact sport.

Accurate diagnosis of minor cartilage injuries with delayed contrast-enhanced computed tomography (CECT) is challenging as poor diffusion and toxicity issues limit the usage of common CT contrast agents. Hence, the design of safe contrast agents with physiochemical properties suitable for fast, deep cartilage imaging is imminent. Herein, a novel cationic bismuth contrast agent (Bi-DOTAPXD) based on dodecane tetraacetic acid (DOTA) was synthesized and examined for CECT of cartilage. The complex was designed to improve diagnosis by utilising a net-positive charge for enhanced permeability through cartilage, inherent low-toxicity and high X-ray attenuation of bismuth. Osteochondral plugs (n = 12), excised from visually intact porcine articular cartilage were immersed in Bi-DOTAPXD (8 mg/mL) and Gd-DOTAPXD (10 mg/mL) contrast agents and scanned with a high-resolution microcomputed tomography scanner at multiple time-points. The mean Bi-DOTAPXD and Gd-DOTAPXD partitions at 45-min time-point were 85.7 ± 35.1 and 69.8 ± 30.2%, and the partitions correlated with the histopathological analysis of cartilage proteoglycan (PG) content (r) at 0.657 and 0.632, respectively. The time diffusion constants (τ) for Bi-DOTAPXD and Gd-DOTA were 121 and 159 min, respectively. Diffusion Bi-DOTAPXD and Gd-DOTAPXD reflected inter-sample variation in cartilage PG content. Cationic Bi-DOTAPXD may have the potential as a CT agent for the diagnosis of cartilage.

Platelet adhesion to blood vessel walls is a key initial event in thrombus formation in both vascular disease processes and prosthetic cardiovascular devices. We extended a deformable multiscale model (MSM) of flowing platelets, incorporating Dissipative Particle Dynamics (DPD) and Coarse-Grained Molecular Dynamics (CGMD) describing molecular-scale intraplatelet constituents and their interaction with surrounding flow, to predict platelet adhesion dynamics under physiological flow shear stresses. Binding of platelet glycoprotein receptor Ibα (GPIbα) to von Willebrand factor (vWF) on the blood vessel wall was modeled by a molecular-level hybrid force field and validated with in vitro microchannel experiments of flowing platelets at 30 dyne/cm2. High frame rate videos of flipping platelets were analyzed with a Semi-Unsupervised Learning System (SULS) machine learning-guided imaging approach to segment platelet geometries and quantify adhesion dynamics parameters. In silico flipping dynamics followed in vitro measurements at 15 and 45 dyne/cm2 with high fidelity, predicting GPIbα-vWF bonding and debonding processes, distribution of bonds strength, and providing a biomechanical insight into initiation of the complex platelet adhesion process. The adhesion model and simulation framework can be further integrated with our established MSMs of platelet activation and aggregation to simulate initial mural thrombus formation on blood vessel walls.

Tetralogy of Fallot (ToF) is characterized by stenosis causing partial obstruction of the right ventricular outflow tract, typically alleviated through the surgical application of a vessel patch made from a biocompatible material. In this study, we use computational simulations to compare the mechanical performance of four patch materials for various stenosis locations. Nine idealized pre-operative ToF geometries were created by imposing symmetrical stenoses on each of three anatomical sub-regions of the pulmonary arteries of three patients with previously repaired ToF. A virtual surgery methodology was implemented to replicate the steps of vessel de-pressurization, surgical patching, and subsequent vessel expansion after reperfusion. Significant differences in patch average stress (p < 0.001) were found between patch materials. Biological patch materials (porcine xenopericardium, human pericardium) exhibited higher patch stresses in comparison to synthetic patch materials (Dacron and PTFE). Observed differences were consistent across the various stenosis locations and were insensitive to patient anatomy.

Laparoscopic surgery is widely used for treating intra-abdominal conditions involving the gallbladder, pancreas, liver, intestines and reproductive organs. Conventional laparoscopy instruments used in manual surgeries usually have straight shafts and four degrees of freedom (DOF) plus grasping. However, these are insufficient for the complete rotation of the instrument tip. This makes it challenging to access difficult-to-reach organs inside the abdomen during the surgeries. A few robotic instruments available in the market have higher maneuverability but are expensive. Instruments incorporating cable-based mechanisms require replacement after a few sterilization cycles. This paper describes a novel, reusable and affordable multi-DOF laparoscopy instrument that provides two additional DOF: (a) wrist articulation about one axis (wristed yaw) and (b) rotation of the jaw after articulation (jaw roll). The wrist can articulate up to 45° and also roll after articulation. The additional degrees of freedom enable better maneuverability, functionality and reach than conventional laparoscopy instruments. Further, the new instrument employs only rigid links, providing better strength and minimal loss of function after multiple sterilizations. The complete design of the novel instrument, followed by its kinematic analysis and force calculations are explained in this paper, concluding with its manufacture and experimental validation.

The anterior cruciate ligament (ACL) is the most commonly injured knee ligament. Surgical reconstruction is the gold standard treatment for ACL ruptures, but 20-50% of patients develop post-traumatic osteoarthritis (PTOA). ACL rupture is thus a well-recognized etiology of PTOA; however, little is known about the initial relationship between ligamentous injury and subsequent PTOA. The goals of this project were to: (1) develop both partial and full models of mid-substance ACL rupture in male and female mice using non-invasive mechanical methods by means of tibial displacement; and (2) to characterize early PTOA changes in the full ACL rupture model. A custom material testing system was utilized to induce either partial or full ACL rupture by means of tibial displacement at 1.6 or 2.0 mm, respectively. Mice were euthanized either (i) immediately post-injury to determine rupture success rates or (ii) 14 days post-injury to evaluate early PTOA progression following full ACL rupture. Our models demonstrated high efficacy in inciting either full or partial ACL rupture in male and female mice within the mid-substance of the ACL. These tools can be utilized for preclinical testing of potential therapeutics and to further our understanding of PTOA following ACL rupture.

Contrast-enhanced magnetic resonance angiography is a vital tool for evaluating vascular pathology. However, concerns about the limitations and safety of gadolinium-based contrast agents have led to an interest in alternative agents. Methemoglobin (metHb) increases the T1-weighted signal intensity of the magnetic resonance image of blood and could provide a safe and effective alternative. MetHb can be produced by the reaction of nitric oxide (NO) gas with oxyhemoglobin followed by natural conversion back to hemoglobin by cytochrome b5 reductase. Since rapid production of metHb via NO has not been studied, the effectiveness of producing metHb via NO delivery to blood was evaluated using a hollow-fiber module. MetHb production began immediately and > 90% conversion was achieved within 10 min. MetHb remained stable for at least 90 min when NO delivery was removed following metHb formation. Comparison of experimental data for metHb formation with model predictions showed that only a fraction of the NO delivered was utilized for metHb production, suggesting an additional fast reaction of NO with other blood constituents. Directly delivering NO to blood for the rapid formation of metHb provides a potential platform for producing metHb as an alternative contrast agent.

In vivo skin exhibits viscoelastic, hyper-elastic and non-linear characteristics. It is under a constant state of non-equibiaxial tension in its natural configuration and is reinforced with oriented collagen fibers, which gives rise to anisotropic behaviour. Understanding the complex mechanical behaviour of skin has relevance across many sectors including pharmaceuticals, cosmetics and surgery. However, there is a dearth of quality data characterizing the anisotropy of human skin in vivo. The data available in the literature is usually confined to limited population groups and/or limited angular resolution. Here, we used the speed of elastic waves travelling through the skin to obtain measurements from 78 volunteers ranging in age from 3 to 93 years old. Using a Bayesian framework allowed us to analyse the effect that age, gender and level of skin tension have on the skin anisotropy and stiffness. First, we propose a new measurement of anisotropy based on the eccentricity of angular data and conclude that it is a more robust measurement when compared to the classic "anisotropic ratio". Our analysis then concluded that in vivo skin anisotropy increases logarithmically with age, while the skin stiffness increases linearly along the direction of Langer Lines. We also concluded that the gender does not significantly affect the level of skin anisotropy, but it does affect the overall stiffness, with males having stiffer skin on average. Finally, we found that the level of skin tension significantly affects both the anisotropy and stiffness measurements employed here. This indicates that elastic wave measurements may have promising applications in the determination of in vivo skin tension. In contrast to earlier studies, these results represent a comprehensive assessment of the variation of skin anisotropy with age and gender using a sizeable dataset and robust modern statistical analysis. This data has implications for the planning of surgical procedures and questions the adoption of universal cosmetic surgery practices for very young or elderly patients.

Gadolinium-based contrast agents (GBCAs) are in widespread use to enhance magnetic resonance imaging for evaluating vascular pathology. However, safety concerns and limitations regarding the use of GBCAs has led to an increased interest in alternative contrast agents. Previously, methemoglobin (metHb) and oxygen-free hemoglobin (HHb) have been shown to increase the T1-weighted signal intensity of blood, which is associated with a decrease in the T1 parameter and an enhanced contrast of the image. Thus, a lower T1 value compared to the baseline value is favorable for imaging. However, it is unknown as to whether metHb or HHb would be a stronger and more appropriate contrast agent and to what extent the T1-weighted signal is affected by concentration. This study evaluated T1-weighted images of blood samples over a range of metHb and HHb concentrations, as well as ferrous nitrosyl hemoglobin (HbIINO) concentrations. Comparison of T1 values from a baseline value of ~ 1500 ms showed that metHb is the strongest contrast agent (T1 ~ 950 ms at 20% metHb) and that HHb is a relatively weak contrast agent (T1 ~ 1450 ms at 20% HHb). This study showed for the first time that HbIINO can provide a contrast effect, although not as strong as metHb but stronger than HHb (T1 estimated as 1250 ms at 20% HbIINO). With metHb providing a viable contrast between 10 and 20%, metHb has the potential to be a safe and effective contrast agent since it can be naturally converted back to hemoglobin.

Knowledge of individual muscle force during strength and conditioning exercises provides deeper understanding of how specific training decisions relate to desired training outcomes. The purpose of this study was to estimate individual muscle forces during hexbar jumps with 0%, 20%, 40%, and 60% of the hexbar deadlift 1-repetition maximum utilizing in vivo motion capture and computational modeling techniques of male participants. Muscle forces for the gluteus maximus, biceps femoris, rectus femoris, vastus intermedius, gastrocnemius, and soleus were estimated via static optimization. Changes in muscle forces over the concentric phase were analyzed across loading conditions using statistical parametric mapping, impulse, and peak values. Conclusions about the effects of load differ between the three analysis methods; therefore, careful selection of analysis method is essential. Peaks may be inadequate in assessing differences in muscle force during dynamic movements. If SPM, assessing point-by-point differences, is combined with impulse, where time of force application is considered, both timepoint and overall loading can be analyzed. The response of individual muscle forces to increases in external load, as assessed by impulse and SPM, includes increased total muscle output, proportionally highest at 20%1RM, and increased absolute force for the vasti and plantarflexors during the concentric phase of hexbar jumps.

Clonogenic assays are routinely used to evaluate the response of cancer cells to external radiation fields, assess their radioresistance and radiosensitivity, estimate the performance of radiotherapy. However, classic clonogenic tests focus on the number of colonies forming on a substrate upon exposure to ionizing radiation, and disregard other important characteristics of cells such their ability to generate structures with a certain shape. The radioresistance and radiosensitivity of cancer cells may depend less on the number of cells in a colony and more on the way cells interact to form complex networks. In this study, we have examined whether the topology of 2D cancer-cell graphs is influenced by ionizing radiation. We subjected different cancer cell lines, i.e. H4 epithelial neuroglioma cells, H460 lung cancer cells, PC3 bone metastasis of grade IV of prostate cancer and T24 urinary bladder cancer cells, cultured on planar surfaces, to increasing photon radiation levels up to 6 Gy. Fluorescence images of samples were then processed to determine the topological parameters of the cell-graphs developing over time. We found that the larger the dose, the less uniform the distribution of cells on the substrate-evidenced by high values of small-world coefficient (cc), high values of clustering coefficient (cc), and small values of characteristic path length (cpl). For all considered cell lines, [Formula: see text] for doses higher or equal to 4 Gy, while the sensitivity to the dose varied for different cell lines: T24 cells seem more distinctly affected by the radiation, followed by the H4, H460 and PC3 cells. Results of the work reinforce the view that the characteristics of cancer cells and their response to radiotherapy can be determined by examining their collective behavior-encoded in a few topological parameters-as an alternative to classical clonogenic assays.

This study focuses on the calcification development and routes of type-1 bicuspid aortic valves based on CT scans and the effect of the unique geometrical shapes of calcium deposits on their fragmentation under balloon valvuloplasty procedures. Towards this goal, the novel Reverse Calcification Technique (RCT), which can predict the calcification progression leading to the current state based on CT scans, is utilized for n = 26 bicuspid aortic valves patients. Two main calcification patterns of type-1 bicuspid aortic valves were identified; asymmetric and symmetric with either partial or full arcs and circles. Subsequently, a calcification fragmentation biomechanical model was introduced to study the balloon valvuloplasty procedure prior to transcatheter aortic valve replacement implantation that allows better device expansion. To achieve this goal, six representative stenotic bicuspid aortic valves of different calcification patterns were investigated. It was found that the distinct geometrical shape of the calcium deposits had a significant effect on the cracks' initiations. Full or partial circle deposits had stronger resistance to fragmentation and mainly remained intact, yet, arc-shaped pattern deposits resulted in multiple cracks in bottleneck regions. The proposed biomechanical computational models could help assess calcification fragmentation patterns toward improving treatment approaches in stenotic bicuspid aortic valve patients, particularly for the off-label use of transcatheter aortic valve replacement.

The endothelium in the coronary arteries is subject to wall shear stress and vessel wall strain, which influences the biology of the arterial wall. This study presents vessel-specific fluid-structure interaction (FSI) models of three coronary arteries, using directly measured experimental geometries and boundary conditions. FSI models are used to provide a more physiologically complete representation of vessel biomechanics, and have been extended to include coronary bending to investigate its effect on shear and strain. FSI both without- and with-bending resulted in significant changes in all computed shear stress metrics compared to CFD (p = 0.0001). Inclusion of bending within the FSI model produced highly significant changes in Time Averaged Wall Shear Stress (TAWSS) + 9.8% LAD, + 8.8% LCx, - 2.0% RCA; Oscillatory Shear Index (OSI) + 208% LAD, 0% LCx, + 2600% RCA; and transverse wall Shear Stress (tSS) + 180% LAD, + 150% LCx and + 200% RCA (all p < 0.0001). Vessel wall strain was homogenous in all directions without-bending but became highly anisotropic under bending. Changes in median cyclic strain magnitude were seen for all three vessels in every direction. Changes shown in the magnitude and distribution of shear stress and wall strain suggest that bending should be considered on a vessel-specific basis in analyses of coronary artery biomechanics.

Commotio cordis is one of the leading causes of sudden cardiac death in youth baseball. Currently, there are chest protector regulations regarding the prevention of Commotio cordis in baseball and lacrosse; however, they are not fully optimized. For the advancement of Commotio cordis safety, it is vital to include various age groups and a variety of impact angles in the testing process. This study employed finite element models and simulated Commotio cordis-inducing baseball collisions for different velocities, impact angles, and age groups. Commotio cordis risk response was characterized in terms of left ventricular strain and pressure, chest band and rib deformation, and force from impact. Normalized rib and chest band deformation when correlated with left ventricular strain resulted in R2 = 0.72, and R2 = 0.76, while left ventricular pressure resulted in R2 = 0.77, R2 = 0.68 across all velocities and impact angles in the child models. By contrast, the resultant reaction force risk metric as used by the National Operating Committee on Standards for Athletic Equipment (NOCSAE) demonstrated a correlation of R2 = 0.20 in the child models to ventricular strain, while illustrating a correlation to pressure of R2 = 0.74. When exploring future revisions to Commotio cordis safety requirements, the inclusion of deformation-related risk metrics at the level of the left ventricle should be considered.

Surgical simulation models have been developed using post-mortem human subjects (PMHS). These models involve the pressurization and ventilation of the PMHS to create a more realistic environment for training and the practice of surgical procedures. The overall objective of this study was to determine the feasibility of a previously developed surgical simulation model to detect soft tissue injuries during a ballistic impact to the torso. One of the main limitations of using PMHS for the assessment of soft tissue injuries in the field of injury biomechanics is the lack of physiological blood flow. To overcome this limitation, the assessment of the surgical simulation model for use in injury biomechanics applications was conducted based on data collected from behind armor blunt trauma (BABT) case studies. Documented injuries in real-world cases included anterior lung contusion, posterior lung contusion, and liver contusion. These real-world injuries were compared to those seen post-impact in the PMHS using pathological and histological techniques. Discussion of limitations and future work is presented.

Myocardial infarction (MI) results in cardiac myocyte death and the formation of a fibrotic scar in the left ventricular free wall (LVFW). Following an acute MI, LVFW remodeling takes place consisting of several alterations in the structure and properties of cellular and extracellular components with a heterogeneous pattern across the LVFW. The normal function of the heart is strongly influenced by the passive and active biomechanical behavior of the LVFW, and progressive myocardial structural remodeling can have a detrimental effect on both diastolic and systolic functions of the LV leading to heart failure. Despite important advances in understanding LVFW passive remodeling in the setting of MI, heterogeneous remodeling in the LVFW active properties and its relationship to organ-level LV function remain understudied. To address these gaps, we developed high-fidelity finite-element (FE) rodent computational cardiac models (RCCMs) of MI using extensive datasets from MI rat hearts representing the heart remodeling from one-week (1-wk) to four-week (4-wk) post-MI timepoints. The rat-specific models (n = 2 for each timepoint) integrate detailed imaging data of the heart geometry, myocardial fiber architecture, and infarct zone determined using late gadolinium enhancement prior to terminal measurements. The computational models predicted a significantly higher level of active tension in remote myocardium in early post-MI hearts (1-wk post-MI) followed by a return to near the control level in late-stage MI (3- and 4-wk post-MI). The late-stage MI rats showed smaller myofiber ranges in the remote region and in-silico experiments using RCCMs suggested that the smaller fiber helicity is consistent with lower contractile forces needed to meet the measured ejection fractions in late-stage MI. In contrast, in-silico experiments predicted that collagen fiber transmural orientation in the infarct region has little influence on organ-level function. In addition, our MI RCCMs indicated that reduced and potentially positive circumferential strains in the infarct region at end-systole can be used to infer information about the time-varying properties of the infarct region. The detailed description of regional passive and active remodeling patterns can complement and enhance the traditional measures of LV anatomy and function that often lead to a gross and limited assessment of cardiac performance. The translation and implementation of our model in patient-specific organ-level simulations offer to advance the investigation of individualized prognosis and intervention for MI.

Specific levator ani muscle imaging measures change with pregnancy and vaginal parity, though entire pelvic floor muscle complex (PFMC) shape variation related to pregnancy-induced and postpartum remodeling has never been quantified. We used statistical shape modeling to compute the 3D variation in PFMC morphology of reproductive-aged nulliparous, late pregnant, and parous women. Pelvic magnetic resonance images were collected retrospectively and PFMCs were segmented. Modes of variation and principal component scores, generated via statistical shape modeling, defined significant morphological variation. Nulliparous (have never given birth), late pregnant (3rd trimester), and parous (have given birth and not currently pregnant) PFMCs were compared via MANCOVA. The overall PFMC shape, mode 2, and mode 3 significantly differed across patient groups (p < 0.001, = 0.002, = 0.001, respectively). This statistical shape analysis described greater perineal and external anal sphincter descent, increased iliococcygeus concavity, and a proportionally wider mid-posterior levator hiatus in late pregnant compared to nulliparous and parous women. The late pregnant group was the most divergent, highlighting differences that likely reduce the mechanical burden of vaginal childbirth. This robust quantification of PFMC shape provides insight to pregnancy and postpartum remodeling and allows for generation of representative non-patient-specific PFMCs that can be used in biomechanical simulations.

Intraventricular hemorrhage is characterized by blood leaking into the cerebral ventricles and mixing with cerebrospinal fluid. A standard treatment method involves inserting a passive drainage catheter, known as an external ventricular drain (EVD), into the ventricle. EVDs have common adverse complications, including the occlusion of the catheter, that may lead to permanent neural damage or even mortality. In order to prevent such complications, a novel dual-lumen catheter (IRRAflow®) utilizing an active fluid exchange mechanism has been recently developed. However, the fluid dynamics of the exchange system have not been investigated. In this study, convective flow in a three-dimensional cerebral lateral ventricle with an inserted catheter is evaluated using an in-house lattice-Boltzmann-based fluid-solid interaction solver. Different treatment conditions are simulated, including injection temperature and patient position. Thermal and gravitational effects on medication distribution are studied using a dye simulator based on a recently-introduced (pseudo)spectral convection-diffusion equation solver. The effects of injection temperature and patient position on catheter performance are presented and discussed in terms of hematoma irrigation, vortical structures, mixing, and medication volume distribution. Results suggest that cold-temperature injections can increase catheter efficacy in terms of dye distribution and irrigation potential, both of which can be further guided by patient positioning.

With the goal of enhancing the early diagnosis of colorectal cancer (CRC) polyps and reducing the risk of mortality in cancer patients, in this article, we present a unique diagnosis framework including a Vision-based Surface Tactile Sensor (VS-TS) and complementary Artificial Intelligence algorithms. Leveraging the morphological characteristics (i.e., shape and texture) and stiffness features of the CRC polyps, the proposed framework is able to reliably and sensitively identify their type and stage. To thoroughly characterize and identify the required VS-TS sensitivity for reliable identification of polyps, we first fabricated three different VS-TSs and qualitatively evaluated their performances on 48 different types of polyp phantoms fabricated based on four different types of realistic CRC polyps and three different materials. Next, to quantitatively compare the performance and sensitivity of the fabricated VS-TSs, we used Support Vector Machine (SVM) algorithm and employed various statistical metrics (i.e., accuracy, reliability, and sensitivity). Next, using the most sensitive VS-TS, we classified the type of tumors using the SVM algorithm and applied the t-Distributed Stochastic Neighbor Embedding algorithm to successfully identify the stiffness of classified polyp phantoms solely based on the output images of the VS-TS sensor. Results demonstrated that an SVM algorithm applied on the image outputs of a VS-TS with a Shore hardness of 00-40 scale is able to classify all types of polyps with > 90% accuracy, sensitivity, and reliability. We also repeated experiments on samples of ex-vivo lamb tripe tissues and successfully verified the high sensitivity and reliability of the proposed framework (i.e., > 94%).

In this study, we have used deep learning techniques to understand the perception of researchers in the healthcare sector about the recently introduced chat generative pre-trained transformer (ChatGPT). Ever since the launch of ChatGPT, there have been various debates over the usage of ChatGPT for research purposes. In this article, using the pre-trained BERT (Bidirectional Encoder Representations from Transformers) model, we performed sentiment analysis and topic modeling to analyze the social media posts of healthcare researchers to understand their emotions towards ChatGPT.

Continuum mechanics-based finite element models of the shoulder aim to quantify the mechanical environment of the joint to aid in clinical decision-making for rotator cuff injury and disease. These models allow for the evaluation of the internal loading of the shoulder, which cannot be measured in-vivo. This study uses human cadaveric rotator cuff samples with surface tendon strain estimates, to validate a heterogeneous finite element model of the supraspinatus-infraspinatus complex during various load configurations. The computational model was considered validated when the absolute difference in average maximum principal strain for the articular and bursal sides for each load condition estimated by the model was no greater than 3% compared to that measured in the biomechanical study. The model can predict the strains for varying infraspinatus loads allowing for the study of load sharing between these two tightly coordinated tendons. The future goal is to use the modularity of this validated model to study the initiation and propagation of rotator cuff tear and other rotator cuff pathologies to ultimately improve care for rotator cuff tear patients.

Thoracic aortic aneurysm (TAA) is characterized by dilation of the aorta that can lead to dissection or rupture. Degradation of elastic fibers is a consistent histopathological feature of TAA that likely contributes to disease progression. Pentagalloyl glucose (PGG) shows promise for stabilizing elastic fibers in abdominal aortic aneurysms, but its efficacy and mechanical effects in the thoracic aorta are unknown. We simulated TAAs using elastase (ELA) to degrade elastic fibers in the mouse ascending aorta and determined the preventative and restorative potential of PGG. Biaxial mechanical tests, constitutive model fitting, and multiphoton imaging were performed on untreated (UNT), PGG, ELA, PGG + ELA, and ELA + PGG treated aortas. PGG treatment alone does not significantly alter mechanical properties or wall structure compared to UNT. ELA treatment alone causes an increase in the unloaded diameter and length, decreased compliance, significant changes in the material constants, and separation of the outer layers of the aortic wall compared to UNT. PGG treatment before or after ELA ameliorates the mechanical and structural changes associated with elastic fiber degradation, with preventative PGG treatment being most effective. These results suggest that PGG is a potential pharmaceutical option to stabilize elastic fibers in TAA.

Six kinematic parameters are needed to fully describe three-dimensional (3D) bone motion at a joint. At the knee, the relative movements of the femur and tibia are often represented by a 1-degree-of-freedom (1-DOF) model with a single flexion-extension axis or a 2-DOF model comprising a flexion-extension axis and an internal-external rotation axis. The primary aim of this study was to determine the accuracy with which 1-DOF and 2-DOF models predict the 3D movements of the femur, tibia and patella during daily activities. Each model was created by fitting polynomial functions to 3D tibiofemoral (TF) and patellofemoral (PF) kinematic data recorded from 10 healthy individuals performing 6 functional activities. Model cross-validation analyses showed that the 2-DOF model predicted 3D knee kinematics more accurately than the 1-DOF model. At the TF joint, mean root-mean-square (RMS) errors across all activities and all participants were 3.4°|mm (deg or mm) for the 1-DOF model and 2.4°|mm for the 2-DOF model. At the PF joint, mean RMS errors were 4.0°|mm and 3.9°|mm for the 1-DOF and 2-DOF models, respectively. These results indicate that a 2-DOF model with two rotations as inputs may be used with confidence to predict the full 3D motion of the knee-joint complex.

The formation of new vascular networks via angiogenesis is a crucial biological mechanism to balance tissue metabolic needs, yet the coordination of factors that influence the guidance of growing neovessels remain unclear. This study investigated the influence of extracellular cues within the immediate environment of sprouting tips over multiple hours and obtained quantitative relationships describing their effects on the growth trajectories of angiogenic neovessels. Three distinct microenvironmental cues-fibril tracks, ECM density, and the presence of nearby cell bodies-were extracted from 3D time series image data. The prominence of each cue was quantified along potential sprout trajectories to predict the response to multiple microenvironmental factors simultaneously. Sprout trajectories significantly correlated with the identified microenvironmental cues. Specifically, ECM density and nearby cellular bodies were the strongest predictors of the trajectories taken by neovessels (p < 0.001 and p = 0.016). Notwithstanding, direction changing trajectories, deviating from the initial neovessel orientation, were significantly correlated with fibril tracks (p = 0.003). Direction changes also occurred more frequently with strong microenvironmental cues. This provides evidence for the first time that local matrix fibril alignment influences changes in sprout trajectories but does not materially contribute to persistent sprouting. Together, our results suggest the microenvironmental cues significantly contribute to guidance of sprouting trajectories. Further, the presented methods quantitatively distinguish the influence of individual microenvironmental stimuli during guidance.

After muscle loss or injury, skeletal muscle tissue has the ability to regenerate and return its function. However, large volume defects in skeletal muscle tissue pose a challenge to regenerate due to the absence of regenerative elements such as biophysical and biochemical cues, making the development of new treatments necessary. One potential solution is to utilize electroactive polymers that can change size or shape in response to an external electric field. Poly(ethylene glycol) diacrylate (PEGDA) is one such polymer, which holds great potential as a scaffold for muscle tissue regeneration due to its mechanical properties. In addition, the versatile chemistry of this polymer allows for the conjugation of new functional groups to enhance its electroactive properties and biocompatibility. Herein, we have developed an electroactive copolymer of PEGDA and acrylic acid (AA) in combination with collagen methacrylate (CMA) to promote cell adhesion and proliferation. The electroactive properties of the CMA + PEGDA:AA constructs were investigated through actuation studies. Furthermore, the biological properties of the hydrogel were investigated in a 14-day in vitro study to evaluate myosin light chain (MLC) expression and metabolic activity of C2C12 mouse myoblast cells. The addition of CMA improved some aspects of material bioactivity, such as MLC expression in C2C12 mouse myoblast cells. However, the incorporation of CMA in the PEGDA:AA hydrogels reduced the sample movement when placed under an electric field, possibly due to steric hindrance from the CMA. Further research is needed to optimize the use of CMA in combination with PEGDA:AA as a potential scaffold for skeletal muscle tissue engineering.

Systolic anterior motion (SAM) of the mitral valve (MV) is a complex pathological phenomenon often occurring as an iatrogenic effect of surgical and transcatheter intervention. While the aortomitral angle has long been linked to SAM, the mechanistic relationship is not well understood. We developed the first ex vivo heart simulator capable of recreating native aortomitral biomechanics, and to generate models of SAM, we performed anterior leaflet augmentation and sequential undersized annuloplasty procedures on porcine aortomitral junctions (n = 6). Hemodynamics and echocardiograms were recorded, and echocardiographic analysis revealed significantly reduced coaptation-septal distances confirming SAM (p = 0.003) and effective manipulation of the aortomitral angle (p < 0.001). Upon increasing the angle in our pathological models, we recorded significant increases (p < 0.05) in both coaptation-septal distance and multiple hemodynamic metrics, such as aortic peak flow and effective orifice area. These results indicate that an increased aortomitral angle is correlated with more efficient hemodynamic performance of the valvular system, presenting a potential, clinically translatable treatment opportunity for reducing the risk and adverse effects of SAM. As the standard of care shifts towards surgical and transcatheter interventions, it is increasingly important to better understand SAM biomechanics, and our advances represent a significant step towards that goal.

Respiratory tract dosimetry predictions for inhalation of tobacco product smoke and aerosols are sensitive to the values of the physicochemical properties of constituents that make up the puff. Physicochemical property values may change significantly with temperature, particularly in the oral cavity and upper airways of the lung, where the puff undergoes adjustments from high temperatures in the tobacco product to reach body temperature. The assumption of fixed property values may introduce uncertainties in the predicted doses in these and other airways of the lung. To obtain a bound for the uncertainties and improve dose predictions, we studied temperature evolution of the inhaled puff in the human respiratory tract during different puff inhalation events. Energy equations were developed for the transport of the puff in the respiratory tract and were solved to find air and droplet temperatures throughout the respiratory tract during two puffing scenarios: 1. direct inhalation of the puff into the lung with no pause in the oral cavity, and 2. puff withdrawal, mouth hold, and puff delivery to the lung via inhalation of dilution air. These puffing scenarios correspond to the majority of smoking scenarios. Model predictions showed that temperature effects were most significant during puff withdrawal. Otherwise, the puff reached thermal equilibrium with the body. Findings from this study will improve predictions of deposition and uptake of puff constituents, and therefore inform inhalation risk assessment from use of electronic nicotine delivery systems (ENDS) and combusted cigarettes.

Gastrointestinal motility patterns can be mapped via electrical signals measured non-invasively on the body surface. However, short-term (≈ 2-4 h) meal response studies as well as long-term monitoring (≥ 24 h) may be hindered by skin irritation inherent with traditional Ag/AgCl pre-gelled ("wet") electrodes. The aim of this work was to investigate the practical utility of using dry electrodes for GI body-surface electrical measurements. To directly compare dry vs. wet electrodes, we simultaneously recorded electrical signals from both types arranged in a 9-electrode array during an ≈ 2.5 h colonic meal-response study. Wavelet-based analyses were used to identify the signature post-meal colonic cyclic motor patterns. Blinded comparison of signal quality was carried out by four expert manual reviewers in order to assess the practical utility of each electrode type for identifying GI activity patterns. Dry electrodes recorded high-quality GI signals with signal-to-noise ratio of 10.0 ± 3.5 dB, comparable to that of wet electrodes (9.9 ± 3.6 dB). Although users rated dry electrodes as slightly more difficult to self-apply, they caused no skin irritation and were thus better tolerated overall. Dry electrodes are a more comfortable alternative to conventional wet electrode systems, and may offer a potentially viable option for long-term GI monitoring studies.

Ulnar collateral ligament reconstruction (UCLR) is frequently performed among injured overhead-throwing athletes. One of the most common graft choices when performing a UCLR is the ipsilateral palmaris longus tendon (PL). The purpose of this study was to investigate the material properties of aseptically processed cadaveric knee collateral ligaments (kMCL) as a potential graft source for UCLR and compare them to the gold standard PL autograft. Each PL and kMCL cadaveric sample was subjected to cyclic preconditioning, stress relaxation, and load-to-failure testing, and the mechanical properties were recorded. PL samples exhibited a greater average decrease in stress compared to the kMCL samples during the stress-relaxation test (p < 0.0001). PL samples also demonstrated a greater average Young's modulus in the linear region of the stress-strain curve compared to the kMCL samples (p < 0.01). The average yield strain and maximum strain of kMCL samples were significantly greater than the PL, p = 0.03 and 0.02, respectively. Both graft materials had comparable maximum toughness and demonstrated a similar ability to deform plastically without rupture. The clinical significance of our result is that prepared knee medial collateral ligament allografts may provide a viable graft material for use in the reconstruction of elbow ligaments.

Degenerative cervical myelopathy (DCM) is the commonest cause of cervical spinal cord dysfunction in older adults and is characterized by spinal cord compression and stress during neck motion. Although surgical decompression eliminates static spinal cord compression, cord stress resulting from flexion-extension motion of the spinal column has not been determined for single and multi-level surgical interventions. The effect of surgery on spinal cord stress is expected to change with the number of surgical levels as well as patient-specific anatomy. Using a MRI-derived patient-specific finite element model, we simulated 1-, 2- and 3-level anterior cervical diskectomy and fusion (ACDF) surgery for DCM. A substantial decrease in spinal cord stress at the level of spinal cord decompression was noted in all simulations. This was associated with a considerable increase in spinal cord stress rostral to the surgical level, and the magnitude of stress was higher in multi-level surgery. Increased spinal cord stress at the rostral adjacent segment correlated with increased segmental range of motion (r = 0.69, p = 0.002) and disk pressure (r = 0.57, p = 0.05). Together, these results indicate that ACDF for DCM is associated with adverse spinal cord stress patterns adjacent to the fusion construct, and further research is needed to determine if the altered stress is associated with clinical outcomes after surgery for DCM.

Ligaments of the knee provide stability and prevent excessive motions of the joint. Rupture of the anterior cruciate ligament (ACL), a common sports injury, results in an altered loading environment for other tissues in the joint, likely leading to their mechanical adaptation. In the collateral ligaments, the patterns and mechanisms of biomechanical adaptation following ACL transection (ACLT) remain unknown. We aimed to characterize the adaptation of elastic and viscoelastic properties of the lateral and medial collateral ligaments eight weeks after ACLT. Unilateral ACLT was performed in six rabbits, and collateral ligaments were harvested from transected and contralateral knee joints after eight weeks, and from an intact control group (eight knees from four animals). The cross-sectional areas were measured with micro-computed tomography. Stepwise tensile stress-relaxation testing was conducted up to 6% final strain, and the elastic and viscoelastic properties were characterized with a fibril-reinforced poroviscoelastic material model. We found that the cross-sectional area of the collateral ligaments in the ACL transected knees increased, the nonlinear elastic collagen network modulus of the LCL decreased, and the amount of fast relaxation in the MCL decreased. Our results indicate that rupture of the ACL leads to an early adaptation of the elastic and viscoelastic properties of the collagen fibrillar network in the collateral ligaments. These adaptations may be important to consider when evaluating whole knee joint mechanics after ACL rupture, and the results aid in understanding the consequences of ACL rupture on other tissues.

Astronauts may pilot a future lunar lander in a standing or upright/reclined seated posture. This study compared kinematics and injury risk for the upright/reclined (30°; 60°) seated vs. standing postures for lunar launch/landing using human body modeling across 30 simulations. While head metrics for standing and upright seated postures were comparable to 30 cm height jumps, those of reclined postures were closer to 60 cm height jumps. Head linear acceleration for 60° reclined posture in the 5 g/10 ms pulse exceeded NASA's tolerance (10.1 g; tolerance: 10 g). Lower extremity metrics exceeding NASA's tolerance in the standing posture (revised tibia index: 0.36-0.53; tolerance: 0.43) were lowered in seated postures (0.00-0.04). Head displacement was higher in standing vs. seated (9.0 cm vs. 2.4 cm forward, 7.0 cm vs. 1.3 cm backward, 2.1 cm vs. 1.2 cm upward, 7.3 cm vs. 0.8 cm downward, 2.4 cm vs. 3.2 cm lateral). Higher arm movement was seen with seated vs. standing (40 cm vs. 25 cm forward, 60 cm vs. 15 cm upward, 30 cm vs. 20 cm downward). Pulse-nature contributed more than 40% to the injury metrics for seated postures compared to 80% in the standing posture. Seat recline angle contributed about 22% to the injury metrics in the seated posture. This study established a computational methodology to simulate the different postures of an astronaut for lunar landings and generated baseline injury risk and body kinematics data.

The performance of a transcatheter aortic valve (TAV) can be evaluated by analyzing the flow field downstream of the valve. However, three dimensional flow and pressure fields, and particle residence time, a quantity closely related to thrombosis risk, are challenging to obtain. This experimental study aims to provide a comprehensive 3D measurement of the flow field downstream of an Edwards SAPIEN 3 using time-resolved 3D particle tracking velocimetry (3D PTV) with Shake-the-Box (STB) algorithm. The valve was deployed in an idealized aorta model and tested in a left heart simulator under physiological conditions. Detailed 3D vortical structures, pressure distributions, and particle residence time were obtained by analyzing the 3D particle tracks. Results have shown large-scale retrograde flow entering the sinuses of the TAV at systole, reducing flow stasis there. However, the 3D particle tracks reveal that the retrograde flow has a high residence time and might have already experienced high shear stress near the main jet. Thus by only focusing on the flow in the sinus region is not sufficient to evaluate the leaflet thrombosis risk, and the flow downstream of the valve should be taken into consideration. The unique perspectives offered by 3D PTV are important when evaluating the performance of the TAVs.

Surgical repair of functional mitral regurgitation (FMR) that occurs in nearly 60% of heart failure (HF) patients is currently performed with undersizing mitral annuloplasty (UMA), which lacks short- and long-term durability. Heterogeneity in valve geometry makes tailoring this repair to each patient challenging, and predictive models that can help with planning this surgery are lacking. In this study, we present a 3D echo-derived computational model, to enable subject-specific, pre-surgical planning of the repair. Three computational models of the mitral valve were created from 3D echo data obtained in three pigs with HF and FMR. An annuloplasty ring model in seven sizes was created, each ring was deployed, and post-repair valve closure was simulated. The results indicate that large annuloplasty rings (> 32 mm) were not effective in eliminating regurgitant gaps nor in restoring leaflet coaptation or reducing leaflet stresses and chordal tension. Smaller rings (≤ 32 mm) restored better systolic valve closure in all investigated cases,but excessive valve tethering and restricted motion of the leaflets were still present. This computational study demonstrates that for effective correction of FMR, the extent of annular reduction differs between subjects, and overly reducing the annulus has deleterious effects on the valve.

Millions of people worldwide suffer from spinal cord injuries (SCIs) and traumatic brain injuries (TBIs) annually. Safety devices meant to protect against SCIs and TBIs, such as helmets, airbags, seat belts, and compliant floors are often evaluated with the use of anthropometric test devices (ATD s); however, there are currently no neck surrogates appropriate for the multiplane loading that often occurs in real-world scenarios leading to injury. As such, our objective in this study was to design and create an anatomically correct functional spinal unit (FSU) that produces a repeatable and biofidelic response to lateral bending, axial rotation, and quasistatic flexion-extension motion. This is a critical step in developing a biofidelic omnidirectional surrogate that can be used in future evaluations of safety devices in transportation, occupational, and sports settings. To create a biofidelic C4-C5 FSU, anatomically accurate C4 and C5 vertebrae were designed and manufactured using a 3D printer using geometry derived from the CT scans of a healthy 31-year-old male. Potential intervertebral disc and ligament surrogate materials were tested in compression and tension, respectively, to select representative materials for the surrogate intervertebral disc and cervical ligaments. The C4-C5 FSU was assembled and tested repeatedly in quasistatic flexion-extension, axial rotation, and lateral bending. Kinematic results were captured and compared to previously published cadaver data. The surrogate disc showed excellent Biofidelity (ISO/TR 9790) in compression, and the surrogate ligaments were within 25 N/mm of linear cadaveric stiffness ranges. The assembled FSU named UBC Neck C4-C5 showed good biofidelity under quasistatic axial rotation, lateral bending, flexion-extension, and coupled motion (ISO/TR 9790). However, the instantaneous centre of rotation was not similar to ex vivo or in vivo published studies. The UBC Neck C4-C5 FSU resulted in good biofidelity ratings and will inform future construction of a full surrogate neck to be used in the testing of head and neck safety equipment.

While astronauts may pilot future lunar landers in a standing posture, the response of the human body under lunar launch and landing-related dynamic loading conditions is not well understood. It is important to consider the effects of active muscles under these loading conditions as muscles stabilize posture while standing. In the present study, astronaut response for a piloted lunar mission in a standing posture was simulated using an active human body model (HBM) with a closed-loop joint-angle based proportional integral derivative controller muscle activation strategy and compared with a passive HBM to understand the effects of active muscles on astronaut body kinematics and injury risk. While head, neck, and lumbar spine injury risk were relatively unaffected by active muscles, the lower extremity injury risk and the head and arm kinematics were significantly changed. Active muscle prevented knee-buckling and spinal slouching and lowered tibia injury risk in the active vs. passive model (revised tibia index: 0.02-0.40 vs. 0.01-0.58; acceptable tolerance: 0.43). Head displacement was higher in the active vs. passive model (11.6 vs. 9.0 cm forward, 6.3 vs. 7.0 cm backward, 7.9 vs. 7.3 cm downward, 3.7 vs. 2.4 cm lateral). Lower arm movement was seen with the active vs. passive model (23 vs. 35 cm backward, 12 vs. 20 cm downward). Overall simulations suggest that the passive model may overpredict injury risk in astronauts for spaceflight loading conditions, which can be improved using the model with active musculature.

The placenta is a critical fetal exchange organ, with a complex branching tree-like structure. Its surface is covered by a single multinucleated cell, the syncytiotrophoblast, which bathes in maternal blood for most of pregnancy. Mechanosensing protein expression by the syncytiotrophoblast at term suggests that shear stress exerted by maternal blood flow may modulate placental development and function. However, it is not known how the mechanosensitive capacity of the syncytiotrophoblast, or the shear stress it experiences, change across gestation. Here, we show that the syncytiotrophoblast expresses both mechanosensitive ion channels (Piezo 1, Polycystin 2, TRPV6) and motor proteins associated with primary cilia (Dynein 1, IFT88, Kinesin 2), with higher staining for all these proteins seen in late first trimester placentae than at term. MicroCT imaging of placental tissue was then used to inform computational models of blood flow at the placentone scale (using a porous media model), and at the villous scale (using explicit flow simulations). These two models are then linked to produce a combined model that allows the variation of shear stress across both these scales simultaneously. This combined model predicts that the range of shear stress on the syncytiotrophoblast is higher in the first-trimester than at term (0.8 dyne/cm2 median stress compared to 0.04 dyne/cm2) when considering both these scales. Together, this suggests that the nature of blood flow through the intervillous space, and the resulting shear stress on the syncytiotrophoblast have important influences on placental morphogenesis and function from early in pregnancy.

Extended-duration cyclic loading of the spine is known to be correlated to lower back pain (LBP). Therefore, it is important to understand how the loading history affects the entire structural behavior of the spine, including the viscoelastic effects. Six human spinal segments (L4L5) were loaded with pure moments up to 7.5 Nm cyclically for half an hour, kept unloaded for 15 min, and loaded with three cycles. This procedure was performed in flexion-extension (FE), axial rotation (AR), and lateral bending (LB) and repeated six times per direction for a total of 18 h of testing per segment. A Long Short-Term Memory (LSTM) Recurrent Neural Network (RNN) was trained to predict the change in the biomechanical response under cyclic loading. A strong positive correlation between the total testing time and the ratio of the third cycle to the last cycle of the loading sequence was found (BT: [Formula: see text] =  0.3469, p = 0.0003, RT: [Formula: see text] =0.1988, p  =   0.0377). The moment-range of motion (RoM) curves could be very well predicted with an RNN ([Formula: see text]=0.988), including the correlation between testing time and testing temperature as inputs. This study shows successfully the feasibility of using RNNs to predict changing moment-RoM curves under cyclic moment loading.

Left ventricular assist devices (LVADs) comprise a primary treatment choice for advanced heart failure patients. Treatment with LVAD is commonly associated with complications like stroke and gastro-intestinal (GI) bleeding, which adversely impacts treatment outcomes, and causes fatalities. The etiology and mechanisms of these complications can be linked to the fact that LVAD outflow jet leads to an altered state of hemodynamics in the aorta as compared to baseline flow driven by aortic jet during ventricular systole. Here, we present a framework for quantitative assessment of aortic hemodynamics in LVAD flows realistic human vasculature, with a focus on quantifying the differences between flow driven by LVAD jet and the physiological aortic jet when no LVAD is present. We model hemodynamics in the aortic arch proximal to the LVAD outflow graft, as well as in the abdominal aorta away from the LVAD region. We characterize hemodynamics using quantitative descriptors of flow velocity, stasis, helicity, vorticity and mixing, and wall shear stress. These are used on a set of 27 LVAD scenarios obtained by parametrically varying LVAD outflow graft anastomosis angles, and LVAD flow pulse modulation. Computed descriptors for each of these scenarios are compared against the baseline flow, and a detailed quantitative characterization of the altered state of hemodynamics due to LVAD operation (when compared to baseline aortic flow) is compiled. These are interpreted using a conceptual model for LVAD flow that distinguishes between flow originating from the LVAD outflow jet (and its impingement on the aorta wall), and flow originating from aortic jet during aortic valve opening in normal physiological state.

Tibiofemoral contact loads are crucial parameters in the onset and progression of osteoarthrosis. While contact loads are frequently estimated from musculoskeletal models, their customization is often limited to scaling musculoskeletal geometry or adapting muscle lines. Moreover, studies have usually focused on superior-inferior contact force without investigating three-dimensional contact loads. Using experimental data from six patients with instrumented total knee arthroplasty (TKA), this study customized a lower limb musculoskeletal model to consider the positioning and the geometry of the implant at knee level. Static optimization was performed to estimate tibiofemoral contact forces and contact moments as well as musculotendinous forces. Predictions from both a generic and a customized model were compared to the instrumented implant measurements. Both models accurately predict superior-inferior (SI) force and abduction-adduction (AA) moment. Notably, the customization improves prediction of medial-lateral (ML) force and flexion-extension (FE) moments. However, there is subject-dependent variability in the prediction of anterior-posterior (AP) force. The customized models presented here predict loads on all joint axes and in most cases improve prediction. Unexpectedly, this improvement was more limited for patients with more rotated implants, suggesting a need for further model adaptations such as muscle wrapping or redefinition of hip and ankle joint centers and axes.

Coronary artery bypass graft surgery is a common intervention for coronary artery disease; however, it suffers from graft failure, and the underlying mechanisms are not fully understood. To better understand the relation between graft hemodynamics and surgical outcomes, we performed computational fluid dynamics simulations with deformable vessel walls in 10 study participants (24 bypass grafts) based on CT and 4D flow MRI one month after surgery to quantify lumen diameter, wall shear stress (WSS), and related hemodynamic measures. A second CT acquisition was performed one year after surgery to quantify lumen remodeling. Compared to venous grafts, left internal mammary artery grafts experienced lower abnormal WSS (< 1 Pa) area one month after surgery (13.8 vs. 70.1%, p = 0.001) and less inward lumen remodeling one year after surgery (- 2.4% vs. - 16.1%, p = 0.027). Abnormal WSS area one month post surgery correlated with percent change in graft lumen diameter one year post surgery (p = 0.030). This study shows for the first time prospectively a correlation between abnormal WSS area one month post surgery and graft lumen remodeling 1 year post surgery, suggesting that shear-related mechanisms may play a role in post-operative graft remodeling and might help explain differences in failure rates between arterial and venous grafts.

Conventional catheter-based interventions for treating peripheral artery disease suffer high failure and complication rates. The mechanical interactions with the anatomy constrain catheter controllability, while their length and flexibility limit their pushability. Also, the 2D X-ray fluoroscopy guiding these procedures fails to provide sufficient feedback about the device location relative to the anatomy. Our study aims to quantify the performance of conventional non-steerable (NS) and steerable (S) catheters in phantom and ex vivo experiments. In a 10 mm diameter, 30 cm long artery phantom model, with four operators, we evaluated the success rate and crossing time in accessing 1.25 mm target channels, the accessible workspace, and the force delivered through each catheter. For clinical relevance, we evaluated the success rate and crossing time in crossing ex vivo chronic total occlusions. For the S and NS catheters, respectively, users successfully accessed 69 and 31% of the targets, 68 and 45% of the cross-sectional area, and could deliver 14.2 and 10.2 g of mean force. Using a NS catheter, users crossed 0.0 and 9.5% of the fixed and fresh lesions, respectively. Overall, we quantified the limitations of conventional catheters (navigation, reachable workspace, and pushability) for peripheral interventions; this can serve as a basis for comparison with other devices.

Shield back-face deformation (BFD) is the result of composite ballistic shields deflecting or absorbing a projectile's energy and deforming towards the user. BFD can result in localized loading to the upper extremity, where the shield is secured to the user. An augmented anthropomorphic test device upper extremity was used to quantify this applied load. Four locations along the upper extremity were tested-the hand, wrist, forearm, and elbow-for investigating differing boundary conditions and their effect on resultant load. Varying stand-off distances, the distance between the back of the shield and the force sensor, were investigated. Digital image correlation was also conducted to measure the dynamic displacement of the shield. The mean peak back-face velocity of the shield was 208.4 ± 38.8 m/s, while the average affected area was 1505 ± 158.3 mm2. Impulse was not significantly affected by anatomical location for the same stand-off distance; however, as stand-off distance decreased, the measured force significantly increased (p < 0.05). Notably, impact duration did not differ significantly for any of the impact scenarios. This is the first step in developing injury criteria for this region resulting from behind shield blunt trauma, and these data will be used for developing injury thresholds in post-mortem human surrogates.

Active muscles play an important role in postural stabilization, and muscle-induced joint stiffening can alter the kinematic response of the human body, particularly that of the lower extremities, under dynamic loading conditions. There are few full-body human body finite element models with active muscles in a standing posture. Thus, the objective of this study was to develop and validate the M50-PS+Active model, an average-male simplified human body model in a standing posture with active musculature. The M50-PS+Active model was developed by incorporating 116 skeletal muscles, as one-dimensional beam elements with a Hill-type material model and closed-loop Proportional Integral Derivative (PID) controller muscle activation strategy, into the Global Human Body Models Consortium (GHBMC) simplified pedestrian model M50-PS. The M50-PS+Active model was first validated in a gravity standing test, showing the effectiveness of the active muscles in maintaining a standing posture under gravitational loading. The knee kinematics of the model were compared against volunteer kinematics in unsuited and suited step-down tests from NASA's active response gravity offload system (ARGOS) laboratory. The M50-PS+Active model showed good biofidelity with volunteer kinematics with an overall CORA score of 0.80, as compared to 0.64 (fair) in the passive M50-PS model. The M50-PS+Active model will serve as a useful tool to study the biomechanics of the human body in vehicle-pedestrian accidents, public transportation braking, and space missions piloted in a standing posture.

This study aims to develop a phantom that simulates the electrical properties of a human blood vessel surrounded by tissues, inside which bubbles can be infused to mimic Decompression Sickness (DCS) conditions. This phantom may be used to calibrate novel electrical methods for bubbles detection in humans and study bubble dynamics during DCS. It may contribute to the limitation of in-vivo trials and time/effort saving, while its use can be extended to other biomedical applications. To facilitate the design of the phantom, we perform first in-vitro measurements in a flow-loop and in-vivo measurements in a swine, in order to detect infused bubbles of a few tenths μm-representing Decompression Sickness conditions-in the test liquid flow and blood flow, respectively, by means of "I-VED" EU patented electrical impedance spectroscopy technique. Results show that the proposed phantom, consisting of a spongy specimen soaked in agar gel in the presence of electrolyte with a hole along it, simulates adequately the electrical properties of a human blood vessel surrounded by tissues. I-VED demonstrates pretty high sensitivity to sense micro-bubbles over the partially conductive vessel walls of the phantom or the isolated animal vein, as well as in the flow-loop: bubbles presence increases electrical impedance and causes intense signal fluctuations around its mean value.

The standard of care for intermediate (Stage II) and advanced (Stages III and IV) non-small cell lung cancer (NSCLC) involves chemotherapy with taxane/platinum derivatives, with or without radiation. Ideally, patients would be screened a priori to allow non-responders to be initially treated with second-line therapies. This evaluation is non-trivial, however, since tumors behave as complex multiscale systems. To address this need, this study employs a multiscale modeling approach to evaluate first-line chemotherapy response of individual patient tumors based on metabolomic analysis of tumor core biopsies obtained during routine clinical evaluation. Model parameters were calculated for a patient cohort as a function of these metabolomic profiles, previously obtained from high-resolution 2DLC-MS/MS analysis. Evaluation metrics were defined to classify patients as Disease-Control (DC) [encompassing complete-response (CR), partial-response (PR), and stable-disease (SD)] and Progressive-Disease (PD) following first-line chemotherapy. Response was simulated for each patient and compared to actual response. The results show that patient classifications were significantly separated from each other, and also when grouped as DC vs. PD and as CR/PR vs. SD/PD, by fraction of initial tumor radius metric at 6 days post simulated bolus drug injection. This study shows that patient first-line chemotherapy response can in principle be evaluated from multiscale modeling integrated with tumor tissue metabolomic data, offering a first step towards individualized lung cancer treatment prognosis.

Occupants exposed to low or moderate crash events can already suffer from whiplash-associated disorders leading to severe and long-lasting symptoms. However, the underlying injury mechanisms and the role of muscle activity are not fully clear. Potential increases in injury risk of non-nominal postures, i.e., rotated head, cannot be evaluated in detail due to the lack of experimental data. Examining changes in neck muscle activity to hold and stabilize the head in a rotated position during pre-crash scenarios might provide a deeper understanding of muscle reflex contributions and injury mechanisms. In this study, the influence of two different head postures (nominal vs. rotation of the head by about 63 ± 9° to the right) on neck muscle activity and head kinematics was investigated in simulated braking experiments inside a driving simulator. The braking scenario was implemented by visualization of the virtual scene using head-mounted displays and a combined translational-rotational platform motion. Kinematics of seventeen healthy subjects was tracked using 3D motion capturing. Surface electromyography were used to quantify muscle activity of left and right sternocleidomastoideus (SCM) and trapezius (TRP) muscles. The results show clear evidence that rotated head postures affect the static as well as the dynamic behavior of muscle activity during the virtual braking event. With head turned to the right, the contralateral left muscles yielded higher base activation and delayed muscle onset times. In contrast, right muscles had much lower activations and showed no relevant changes in muscle activation between nominal and rotated head position. The observed delayed muscle onset times and increased asymmetrical muscle activation patterns in the rotated head position are assumed to affect injury mechanisms. This could explain the prevalence of rotated head postures during a crash reported by patients suffering from WAD. The results can be used for validating the active behavior of human body models in braking simulations with nominal and rotated head postures, and to gain a deeper understanding of neck injury mechanisms.

Fetuses with critical aortic stenosis (FAS) are at high risk of progression to HLHS by the time of birth (and are thus termed "evolving HLHS"). An in-utero catheter-based intervention, fetal aortic valvuloplasty (FAV), has shown promise as an intervention strategy to circumvent the progression, but its impact on the heart's biomechanics is not well understood. We performed patient-specific computational fluid dynamic (CFD) simulations based on 4D fetal echocardiography to assess the changes in the fluid mechanical environment in the FAS left ventricle (LV) directly before and 2 days after FAV. Echocardiograms of five FAS cases with technically successful FAV were retrospectively analysed. FAS compromised LV stroke volume and ejection fraction, but FAV rescued it significantly. Calculations to match simulations to clinical measurements showed that FAV approximately doubled aortic valve orifice area, but it remained much smaller than in healthy hearts. Diseased LVs had mildly stenotic mitral valves, which generated fast and narrow diastolic mitral inflow jet and vortex rings that remained unresolved directly after FAV. FAV further caused aortic valve damage and high-velocity regurgitation. The high-velocity aortic regurgitation jet and vortex ring caused a chaotic flow field upon impinging the apex, which drastically exacerbated the already high energy losses and poor flow energy efficiency of FAS LVs. Two days after the procedure, FAV did not alter wall shear stress (WSS) spatial patterns of diseased LV but elevated WSS magnitudes, and the poor blood turnover in pre-FAV LVs did not significantly improve directly after FAV. FAV improved FAS LV's flow function, but it also led to highly chaotic flow patterns and excessively high energy losses due to the introduction of aortic regurgitation directly after the intervention. Further studies analysing the effects several weeks after FAV are needed to understand the effects of such biomechanics on morphological development.

It is very important for clinicians to provide restorative treatments that provide durability for endodontically treated teeth. Trauma, occlusal premature contact, and features of teeth are some of the issues that can cause vertical root fractures (VRFs) in root canal-treated teeth. The aim of this 3-D study was to compare stress distribution on mandibular premolar teeth when using a variety of post designs instrumented with different rotary systems. Six mandibular premolar teeth were instrumented with the following tools: ProTaper Next, WaveOne (WO), Reciproc (R), ReciprocBlue (RB), F6-Skytaper, and TF-Adaptive. Teeth were scanned using cone beam computed tomography (CBCT) and the images were transferred to the Catia V5R25 software. Data were recorded in a stereolithography (STL) format. Four different post systems were used, fabricated from metal, fiber, zirconia, and titanium, respectively. Dentin, gutta, post, core, and crown models were added to the solid model. ANSYS V17.2 finite element analysis (FEA) software was used to determine stress distribution on each assembly. Finite analysis models were created that allowed for the calculation of stress distribution of 250-N loading at a 45° angle and vertical in relation to the roots. The maximum principal stress and von Mises values were higher under oblique loading on the roots. The F6-Skytaper and WO systems showed lower stress than other systems. The TF-Adaptive instrument showed higher stress distribution than the other models. Fiber and titanium posts showed lower stress than others. The F6-Skytaper, R, and RB instruments were found to be most effective in terms of displacement of the crown, resulting in the lowest stress values. Fiber and titanium posts showed better results than other post systems, while root canals instrumented with the F6-Skytaper and WO instruments were less likely to result in root fractures.

To improve abdominal aortic aneurysm (AAA) rupture risk assessment, a large, longitudinal study on AAA hemodynamics and biomechanics is necessary, using personalized fluid-structure interaction (FSI) modeling. 3-dimensional, time-resolved ultrasound (3D+t US) is the preferred image modality to obtain the patient-specific AAA geometry for such a study, since it is safe, affordable and provides temporal information. However, the 3D+t US field-of-view (FOV) is limited and therefore often fails to capture the inlet and aorto-iliac bifurcation geometry. In this study, a framework was developed to add parametric inlet and bifurcation geometries to the abdominal aortic aneurysm geometry by employing dataset statistics and parameters of the AAA geometry. The impact of replacing the patient-specific inlet and bifurcation geometries, acquired using computed tomography (CT) scans, by parametric geometries was evaluated by examining the differences in hemodynamics (systolic and time-averaged wall shear stress and oscillatory shear index) in the aneurysm region. The results show that the inlet geometry has a larger effect on the AAA hemodynamics (median differences of 7.5 to 18.8%) than the bifurcation geometry (median differences all below 1%). Therefore, it is not feasible to replace the patient-specific inlet geometry by a generic one. Future studies should investigate the possibilities of extending the proximal FOV of 3D+t US. However, this study did show the feasibility of adding a parametric bifurcation geometry to the aneurysm geometry. After extending the proximal FOV, the obtained framework can be used to extract AAA geometries from 3D+t US for FSI simulations, despite the absence of the bifurcation geometry.

Left atrial ligation (LAL) of the chick embryonic heart is a model of the hypoplastic left heart syndrome (HLHS) where a purely mechanical intervention without genetic or pharmacological manipulation is employed to initiate cardiac malformation. It is thus a key model for understanding the biomechanical origins of HLHS. However, its myocardial mechanics and subsequent gene expressions are not well-understood. We performed finite element (FE) modeling and single-cell RNA sequencing to address this. 4D high-frequency ultrasound imaging of chick embryonic hearts at HH25 (ED 4.5) were obtained for both LAL and control. Motion tracking was performed to quantify strains. Image-based FE modeling was conducted, using the direction of the smallest strain eigenvector as the orientations of contractions, the Guccione active tension model and a Fung-type transversely isotropic passive stiffness model that was determined via micro-pipette aspiration. Single-cell RNA sequencing of left ventricle (LV) heart tissues was performed for normal and LAL embryos at HH30 (ED 6.5) and differentially expressed genes (DEG) were identified.After LAL, LV thickness increased by 33%, strains in the myofiber direction increased by 42%, while stresses in the myofiber direction decreased by 50%. These were likely related to the reduction in ventricular preload and underloading of the LV due to LAL. RNA-seq data revealed potentially related DEG in myocytes, including mechano-sensing genes (Cadherins, NOTCH1, etc.), myosin contractility genes (MLCK, MLCP, etc.), calcium signaling genes (PI3K, PMCA, etc.), and genes related to fibrosis and fibroelastosis (TGF-β, BMP, etc.). We elucidated the changes to the myocardial biomechanics brought by LAL and the corresponding changes to myocyte gene expressions. These data may be useful in identifying the mechanobiological pathways of HLHS.

Blast-induced auditory trauma is a common injury in military service members and veterans that leads to hearing loss. While the inner ear response to blast exposure is difficult to characterize experimentally, computational models have advanced to predict blast wave transmission from the ear canal to the cochlea; however, published models have either straight or spiral cochlea with fluid-filled two chambers. In this paper, we report the recently developed 3D finite element (FE) model of the human ear mimicking the anatomical structure of the 3-chambered cochlea. The model consists of the ear canal, middle ear, and two and a half turns of the cochlea with three chambers separated by the Reissner's membrane (RM) and the basilar membrane (BM). The blast overpressure measured from human temporal bone experiments was applied at the ear canal entrance and the Fluent/Mechanical coupled fluid-structure interaction analysis was conducted in ANSYS software. The FE model-derived results include the pressure in the canal near the tympanic membrane (TM) and the intracochlear pressure at scala vestibuli, the TM displacement, and the stapes footplate (SFP) displacement, which were compared with experimentally measured data in human temporal bones. The validated model was used to predict the biomechanical response of the ear to blast overpressure: distributions of the maximum strain and stress within the TM, the BM displacement variation from the base to apex, and the energy flux or total energy entering the cochlea. The comparison of intracochlear pressure and BM displacement with those from the FE model of 2-chambered cochlea indicated that the 3-chamber cochlea model with the RM and scala media chamber improved our understanding of cochlea mechanics. This most comprehensive FE model of the human ear has shown its capability to predict the middle ear and cochlea responses to blast overpressure which will advance our understanding of auditory blast injury.

There is an increasing demand to develop predictive medicine through the creation of predictive models and digital twins of the different body organs. To obtain accurate predictions, real local microstructure, morphology changes and their accompanying physiological degenerative effects must be taken into account. In this article, we present a numerical model to estimate the long-term aging effect on the human intervertebral disc response by means of a microstructure-based mechanistic approach. It allows to monitor in-silico the variations in disc geometry and local mechanical fields induced by age-dependent long-term microstructure changes. Both lamellar and interlamellar zones of the disc annulus fibrosus are constitutively represented by considering the main underlying microstructure features in terms of proteoglycans network viscoelasticity, collagen network elasticity (along with content and orientation) and chemical-induced fluid transfer. With age, a noticeable increase in shear strain is especially observed in the posterior and lateral posterior regions of the annulus which is in correlation with the high vulnerability of elderly people to back problems and posterior disc hernia. Important insights about the relation between age-dependent microstructure features, disc mechanics and disc damage are revealed using the present approach. These numerical observations are hardly obtainable using current experimental technologies which makes our numerical tool useful for patient-specific long-term predictions.

Hemifacial microsomia (HFM), one of the most common congenital facial anomalies, was usually treated with the bilateral sagittal split osteotomy (BSSO) procedure to correct the asymmetric appearance and malocclusion of the mandible. However, the frequent post-operative relapse incidents would lead to the restoration of the mandibular segment to its preoperative position and failure of the BSSO procedure. In this study, a customized asymmetric fixed plate (CAF plate) was developed to resist relapse due to hemifacial microsomia occlusal forces and the different muscular traction forces on both sides of the mandible. For the actual HFM case in this study, the reconstructed mandibular segmental bone model was fixed using BSSO with a rectangular plate (the original CAF plate appearance) in the topology optimization analysis. With the topology optimization technique, the CAF plate was designed with a lightweight profile and excellent structural strength in consideration of the HFM asymmetrical muscle traction and occlusal force. Using biomechanical simulations, the von-Mises stress and CAF plate mandibular segment displacement and the miniplate were compared to evaluate which had superior relapse resistance. In the in-vitro biomechanical test, a fatigue force of 250,000 cycles and a constant muscle traction force were applied to the HFM mandibular model, which was fixed with the CAF plate fabricated using metal 3D printing (selective laser melting, SLM) to obtain the mandibular segment displacement as a relapse assessment. The topology optimization analysis showed that the CAF plate has the best characteristics, light weight and structural strength with 30% volume retention. The biomechanical analysis showed that the maximum von Mises stress of the mini-plate was 2.71 times higher than that of the CAF plate. The relapse displacement of the mandibular segment fixed with the mini-plate was 1.62 times higher than that fixed with the CAF plate. The CAF plate ability to resist relapse was confirmed by the biomechanical testing results so that only 0.29 mm of recurrence displacement was observed in the mandibular segment. The results indicated that the CAF plate structural strength and resistance to relapse was significantly better than that of the mini-plate. This study developed a customized asymmetric fixation plate for hemifacial microsomia, integrating topology optimization, metal 3D printing, and in vitro biomechanical testing to resist occlusal forces and differential muscle traction on both sides of the mandible to reduce relapse and improve fixation stability.

Iliac wing fractures due to lap belt loading have been identified in laboratory tests for almost 50 years and an analysis of recent data suggests these injuries are also occurring in the field. With the introduction of highly autonomous vehicles on the horizon, vehicle manufacturers are exploring open cabin concepts that permit reclined postures and separation of the occupant from the knee bolster and instrument panel. This will result in greater reliance on the lap belt and lap belt/pelvis loading to restrain occupants. No injury criteria exist for iliac wing fractures resulting from lap belt loading like that seen in frontal crash conditions. This study tested the tolerance of isolated iliac wings in a controlled lap belt-like loading environment while incorporating the effect of loading angle after analyzing lap belt loading experiments from a previous study. Twenty-two iliac wings were tested; nineteen of them sustained fracture (exact), but the loading input was insufficient to cause fracture in the other three (right censored). The fracture tolerance of the tested specimens ranged widely (1463-8895 N) and averaged 4091 N (SD 2381 N). Injury risk functions were created by fitting Weibull survival models to data that integrated censored and exact failure observations.