Flexible, Biodegradable, and Wireless Magnetoelectric Paper for Simple In Situ Personalization of Bioelectric Implants.

Bioelectronic implants delivering electrical stimulation offer an attractive alternative to traditional pharmaceuticals in electrotherapy. However, achieving simple, rapid, and cost-effective personalization of these implants for customized treatment in unique clinical and physical scenarios presents a substantial challenge. This challenge is further compounded by the need to ensure safety and minimal invasiveness, requiring essential attributes such as flexibility, biocompatibility, lightness, biodegradability, and wireless stimulation capability. Here, a flexible, biodegradable bioelectronic paper with homogeneously distributed wireless stimulation functionality for simple personalization of bioelectronic implants is introduced. The bioelectronic paper synergistically combines i) lead-free magnetoelectric nanoparticles (MENs) that facilitate electrical stimulation in response to external magnetic field and ii) flexible and biodegradable nanofibers (NFs) that enable localization of MENs for high-selectivity stimulation, oxygen/nutrient permeation, cell orientation modulation, and biodegradation rate control. The effectiveness of wireless electrical stimulation in vitro through enhanced neuronal differentiation of neuron-like PC12 cells and the controllability of their microstructural orientation are shown. Also, scalability, design flexibility, and rapid customizability of the bioelectronic paper are shown by creating various 3D macrostructures using simple paper crafting techniques such as cutting and folding. This platform holds promise for simple and rapid personalization of temporary bioelectronic implants for minimally invasive wireless stimulation therapies.

[Short-term efficacy of digitally-assisted traditional Chinese medicine manual reduction combined with 3D printed splint in the treatment of AO type-A distal radius fractures].

Objective To explore the short-term efficacy of digitally-assisted traditional Chinese medicine manual reduction combined with 3D printed splint in the treatment of AO type-A distal radius fractures, and explore the quantification of traditional Chinese medicine manual reduction and personalized improvement of splinting. Methods The clinical data of 50 patients with AO type-A distal radius fractures, who received treatment at the outpatient department of Cangzhou Integrated Traditional Chinese and Western Medicine Hospital in Hebei Province, were retrospective analyzed. The patient cohort included 22 females and 28 males, with ages ranging from 25 to 75 years old. Among them, 27 cases presented with distal radius fractures on the left side, and 24 cases on the right side. The patients were categorized into two groups: treatment group (n=25) and control group(n=25). There were 13 males and 12 females in the treatment group, with an average age of (56.2±5.5) years old. Treatment approach for this group involved several steps. Initially, Mimics Research software was used to conduct comprehensive analysis of complete CT data from the affected limb, resulting in the creation of a three-dimensional model. Subsequently, 3D models of the bones and skin contours, stored as STL format files, were imported into the Materialise Magics 23.0 software for model processing and repair. This facilitated the simulation of reduction and recording of displacement data, effectively generating a "digital prescription" to guide and quantify traditional Chinese medicine manipulation procedures. Finally, a personalized 3D printed splint was applied for fixation treatment. There were 15 males and 10 females in the control group, with an average age of (53.32±5.28) years old. These patients were treated with manualreduction combined with traditional splinting. The clinical efficacy of the two groups was assessed in terms of fracture reduction quality, fracture healing time, Gartland-Werley wrist joint score and X-ray parameters (palminclination angle, ulnar deviation angle, radius height) at 6 weeks post-operatively. Results The treatment group exhibited a shorter duration for achieving clinical healing compared to the control group (P<0.05). Six weeks post-operatively, the treatment group demonstrated higher wrist joint function scores, and a higher proportion of excellent and good outcomes than the control group(P<0.05). The treatment group was superior to the control group in terms of imaging parameters 6 weeks post-operatively (P<0.05). Conclusion By quantifying skin contours through digital simulation prescription reduction, a personalized 3D printed splint is developed to effectively stabilize fractures, enhancing localized fixation while ensuring greater adherence, stability, and comfort. This innovative approach offers personalized treatment for AO type-A distal radius fractures and presents a novel, precise treatment strategy for consideration.

On-chip 3D neuromuscular model for drug screening and precision medicine in neuromuscular disease.

This protocol describes the design, fabrication and use of a 3D physiological and pathophysiological motor unit model consisting of motor neurons coupled to skeletal muscles interacting via the neuromuscular junction (NMJ) within a microfluidic device. This model facilitates imaging and quantitative functional assessment. The 'NMJ chip' enables real-time, live imaging of axonal outgrowth, NMJ formation and muscle maturation, as well as synchronization of motor neuron activity and muscle contraction under optogenetic control for the study of normal physiological events. The proposed protocol takes ~2-3 months to be implemented. Pathological behaviors associated with various neuromuscular diseases, such as regression of motor neuron axons, motor neuron death, and muscle degradation and atrophy can also be recapitulated in this system. Disease models can be created by the use of patient-derived induced pluripotent stem cells to generate both the motor neurons and skeletal muscle cells used. This is demonstrated by the use of cells from a patient with sporadic amyotrophic lateral sclerosis but can be applied more generally to models of neuromuscular disease, such as spinal muscular atrophy, NMJ disorder and muscular dystrophy. Models such as this hold considerable potential for applications in precision medicine, drug screening and disease risk assessment.

Efficacy of electrical polarization on a rat femoral bone defect model with a custom-made external fixator.

BACKGROUND: We have developed a technology to electrically polarize living bone. OBJECTIVE: The effects of stored electrical charge in electrical polarized bone on the facilitation of new bone formation were assayed. METHODS: Stimulated depolarized current measurement was performed in electrically polarized and nonpolarized femora of SD rats. These bone specimens were implanted into bone defects of the rat femora and fixed with a custom-made external fixator. X-ray imaging of the implant was performed every week. After 3 weeks, micro-CT scanning was performed to evaluate the displacement rate. Histological observation was performed, and the occupancy ratio of the newly formed bone was calculated from tissue specimens stained with Villanueva's Goldner method. RESULTS: There was a tendency for the displacement rate of the implant to be smaller and the occupancy ratio of the newly formed bone to be larger, especially at the distal end, in the polarized group compared with the nonpolarized group. The time of callus appearance was significantly earlier in the polarized group than in the nonpolarized group, and bridging callus grew from the distal to the proximal end. CONCLUSIONS: Bone specimens can be electrically polarized, and the stored electrical charge can work effectively to facilitate new bone formation.

User Models for Personalized Physical Activity Interventions: Scoping Review.

BACKGROUND: Fitness devices have spurred the development of apps that aim to motivate users, through interventions, to increase their physical activity (PA). Personalization in the interventions is essential as the target users are diverse with respect to their activity levels, requirements, preferences, and behavior. OBJECTIVE: This review aimed to (1) identify different kinds of personalization in interventions for promoting PA among any type of user group, (2) identify user models used for providing personalization, and (3) identify gaps in the current literature and suggest future research directions. METHODS: A scoping review was undertaken by searching the databases PsycINFO, PubMed, Scopus, and Web of Science. The main inclusion criteria were (1) studies that aimed to promote PA; (2) studies that had personalization, with the intention of promoting PA through technology-based interventions; and (3) studies that described user models for personalization. RESULTS: The literature search resulted in 49 eligible studies. Of these, 67% (33/49) studies focused solely on increasing PA, whereas the remaining studies had other objectives, such as maintaining healthy lifestyle (8 studies), weight loss management (6 studies), and rehabilitation (2 studies). The reviewed studies provide personalization in 6 categories: goal recommendation, activity recommendation, fitness partner recommendation, educational content, motivational content, and intervention timing. With respect to the mode of generation, interventions were found to be semiautomated or automatic. Of these, the automatic interventions were either knowledge-based or data-driven or both. User models in the studies were constructed with parameters from 5 categories: PA profile, demographics, medical data, behavior change technique (BCT) parameters, and contextual information. Only 27 of the eligible studies evaluated the interventions for improvement in PA, and 16 of these concluded that the interventions to increase PA are more effective when they are personalized. CONCLUSIONS: This review investigates personalization in the form of recommendations or feedback for increasing PA. On the basis of the review and gaps identified, research directions for improving the efficacy of personalized interventions are proposed. First, data-driven prediction techniques can facilitate effective personalization. Second, use of BCTs in automated interventions, and in combination with PA guidelines, are yet to be explored, and preliminary studies in this direction are promising. Third, systems with automated interventions also need to be suitably adapted to serve specific needs of patients with clinical conditions. Fourth, previous user models focus on single metric evaluations of PA instead of a potentially more effective, holistic, and multidimensional view. Fifth, with the widespread adoption of activity monitoring devices and mobile phones, personalized and dynamic user models can be created using available user data, including users' social profile. Finally, the long-term effects of such interventions as well as the technology medium used for the interventions need to be evaluated rigorously.

[Medicine 4.0: examples of applications of electronics, information technology and microsystems in modern medicine]. / « Médecine 4.0 ¼ - Exemples d'application de l'électronique, de la technologie de l'information et des microsystèmes dans la médecine moderne.

The electronic advances of the last hundred years have made enormous contributions to medical research and the development of new therapeutic methods. In recent years in particular, it has been demonstrated that intelligent sensors, with appropriate radio interfaces, will soon allow diagnostic and therapeutic processes in medicine to be linked to one another - this will enable the development of completely new forms of therapy [1]. This new "Medicine 4.0" was the subject of a first article in the series, which presented the progress achieved through the merging of microsensor technology, microelectronics, information and communication technologies, with a particular focus on the case of personalized chemotherapy. The purpose of this new article is to present more practical applications of these new therapeutic methods.

Innovation, productivity, and pricing: Capturing value from precision medicine technology in Canada.

For new technology and innovation such as precision medicine to become part of the solution for the fiscal sustainability of Canadian Medicare, decision-makers need to change how services are priced rather than trying to restrain emerging technologies like precision medicine for short-term cost savings. If provincial public payers shift their thinking to be public purchasers, value considerations would direct reform of the reimbursement system to have prices that adjust with technologically driven productivity gains. This strategic shift in thinking is necessary if Canadians are to benefit from the promised benefits of innovations like precision medicine.

Personalized nutrition diagnostics at the point-of-need.

Micronutrient deficiency is widespread and negatively impacts morbidity, mortality, and quality of life globally. On-going advancements in nutritional biomarker discovery are enabling objective and accurate assessment of an individual's micronutrient and broader nutritional status. The vast majority of such assessment however still needs to be conducted in traditional centralized laboratory facilities which are not readily accessible in terms of cost and time in both the developed and developing countries. Lab-on-a-chip (LOC) technologies are enabling an increasing number of biochemical reactions at the point-of-need (PON) settings, and can significantly improve the current predicament in nutrition diagnostics by allowing rapid evaluation of one's nutritional status and providing an easy feedback mechanism for tracking changes in diet or supplementation. We believe that nutrition diagnostics represents a particularly appealing opportunity over other PON applications for two reasons: (1) healthy ranges for many micronutrients are well defined which allows for an unbiased diagnosis, and (2) many deficiencies can be reversed through changes in diet or supplementation before they become severe. In this paper, we provide background on nutritional biomarkers used in nutrition diagnostics and review the emerging technologies that exploit them at the point-of-need.

Integrated Care and Connected Health Approaches Leveraging Personalised Health through Big Data Analytics.

Integrated care and connected health are two fast evolving concepts that have the potential to leverage personalised health. From the one side, the restructuring of care models and implementation of new systems and integrated care programs providing coaching and advanced intervention possibilities, enable medical decision support and personalized healthcare services. From the other side, the connected health ecosystem builds the means to follow and support citizens via personal health systems in their everyday activities and, thus, give rise to an unprecedented wealth of data. These approaches are leading to the deluge of complex data, as well as in new types of interactions with and among users of the healthcare ecosystem. The main challenges refer to the data layer, the information layer, and the output of information processing and analytics. In all the above mentioned layers, the primary concern is the quality both in data and information, thus, increasing the need for filtering mechanisms. Especially in the data layer, the big biodata management and analytics ecosystem is evolving, telemonitoring is a step forward for data quality leverage, with numerous challenges still left to address, partly due to the large number of micro-nano sensors and technologies available today, as well as the heterogeneity in the users' background and data sources. This leads to new R&D pathways as it concerns biomedical information processing and management, as well as to the design of new intelligent decision support systems (DSS) and interventions for patients. In this paper, we illustrate these issues through exemplar research targeting chronic patients, illustrating the current status and trends in PHS within the integrated care and connected care world.

Improving Tumor Treating Fields Treatment Efficacy in Patients With Glioblastoma Using Personalized Array Layouts.

PURPOSE: To investigate tumors of different size, shape, and location and the effect of varying transducer layouts on Tumor Treating Fields (TTFields) distribution in an anisotropic model. METHODS AND MATERIALS: A realistic human head model was generated from MR images of 1 healthy subject. Four different virtual tumors were placed at separate locations. The transducer arrays were modeled to mimic the TTFields-delivering commercial device. For each tumor location, varying array layouts were tested. The finite element method was used to calculate the electric field distribution, taking into account tissue heterogeneity and anisotropy. RESULTS: In all tumors, the average electric field induced by either of the 2 perpendicular array layouts exceeded the 1-V/cm therapeutic threshold value for TTFields effectiveness. Field strength within a tumor did not correlate with its size and shape but was higher in more superficial tumors. Additionally, it always increased when the array was adapted to the tumor's location. Compared with a default layout, the largest increase in field strength was 184%, and the highest average field strength induced in a tumor was 2.21 V/cm. CONCLUSIONS: These results suggest that adapting array layouts to specific tumor locations can significantly increase field strength within the tumor. Our findings support the idea of personalized treatment planning to increase TTFields efficacy for patients with GBM.

A patient-specific aperture system with an energy absorber for spot scanning proton beams: Verification for clinical application.

PURPOSE: In the authors' proton therapy system, the patient-specific aperture can be attached to the nozzle of spot scanning beams to shape an irradiation field and reduce lateral fall-off. The authors herein verified this system for clinical application. METHODS: The authors prepared four types of patient-specific aperture systems equipped with an energy absorber to irradiate shallow regions less than 4 g/cm(2). The aperture was made of 3-cm-thick brass and the maximum water equivalent penetration to be used with this system was estimated to be 15 g/cm(2). The authors measured in-air lateral profiles at the isocenter plane and integral depth doses with the energy absorber. All input data were obtained by the Monte Carlo calculation, and its parameters were tuned to reproduce measurements. The fluence of single spots in water was modeled as a triple Gaussian function and the dose distribution was calculated using a fluence dose model. The authors compared in-air and in-water lateral profiles and depth doses between calculations and measurements for various apertures of square, half, and U-shaped fields. The absolute doses and dose distributions with the aperture were then validated by patient-specific quality assurance. Measured data were obtained by various chambers and a 2D ion chamber detector array. RESULTS: The patient-specific aperture reduced the penumbra from 30% to 70%, for example, from 34.0 to 23.6 mm and 18.8 to 5.6 mm. The calculated field width for square-shaped apertures agreed with measurements within 1 mm. Regarding patient-specific aperture plans, calculated and measured doses agreed within -0.06% ± 0.63% (mean ± SD) and 97.1% points passed the 2%-dose/2 mm-distance criteria of the γ-index on average. CONCLUSIONS: The patient-specific aperture system improved dose distributions, particularly in shallow-region plans.

From Wearable Sensors to Smart Implants--Toward Pervasive and Personalized Healthcare.

OBJECTIVE: This paper discusses the evolution of pervasive healthcare from its inception for activity recognition using wearable sensors to the future of sensing implant deployment and data processing. METHODS: We provide an overview of some of the past milestones and recent developments, categorized into different generations of pervasive sensing applications for health monitoring. This is followed by a review on recent technological advances that have allowed unobtrusive continuous sensing combined with diverse technologies to reshape the clinical workflow for both acute and chronic disease management. We discuss the opportunities of pervasive health monitoring through data linkages with other health informatics systems including the mining of health records, clinical trial databases, multiomics data integration, and social media. CONCLUSION: Technical advances have supported the evolution of the pervasive health paradigm toward preventative, predictive, personalized, and participatory medicine. SIGNIFICANCE: The sensing technologies discussed in this paper and their future evolution will play a key role in realizing the goal of sustainable healthcare systems.

A flexible platform for biofeedback-driven control and personalization of electrical nerve stimulation therapy.

Electrical vagus nerve stimulation is a treatment alternative for many epileptic and depressed patients whose symptoms are not well managed with pharmaceutical therapy. However, the fixed stimulus, open loop dosing mechanism limits its efficacy and precludes major advances in the quality of therapy. A real-time, responsive form of vagus nerve stimulation is needed to control nerve activation according to therapeutic need. This personalized approach to therapy will improve efficacy and reduce the number and severity of side effects. We present autonomous neural control, a responsive, biofeedback-driven approach that uses the degree of measured nerve activation to control stimulus delivery. We demonstrate autonomous neural control in rats, showing that it rapidly learns how to most efficiently activate any desired proportion of vagal A, B, and/or C fibers over time. This system will maximize efficacy by minimizing patient response variability and by minimizing therapeutic failures resulting from longitudinal decreases in nerve activation with increasing durations of treatment. The value of autonomous neural control equally applies to other applications of electrical nerve stimulation.

Active multispectral imaging system for photodiagnosis and personalized phototherapies.

The proposed system has been designed to identify dermatopathologies or to apply personalized phototherapy treatments. The system emits electromagnetic waves in different spectral bands in the range of visible and near infrared to irradiate the target (skin or any other object) to be spectrally characterized. Then, an imaging sensor measures the target response to the stimulus at each spectral band and, after processing, the system displays in real time two images. In one of them the value of each pixel corresponds to the more reflected wavenumber whereas in the other image the pixel value represents the energy absorbed at each band. The diagnosis capability of this system lies in its multispectral design, and the phototherapy treatments are adapted to the patient and his lesion by measuring his absorption capability. This "in situ" absorption measurement allows us to determine the more appropriate duration of the treatment according to the wavelength and recommended dose. The main advantages of this system are its low cost, it does not have moving parts or complex mechanisms, it works in real time, and it is easy to handle. For these reasons its widespread use in dermatologist consultation would facilitate the work of the dermatologist and would improve the efficiency of diagnosis and treatment. In fact the prototype has already been successfully applied to pathologies such as carcinomas, melanomas, keratosis, and nevi.

[Individualised correction of presbyopia by the use of phacoemulsification: monovision and multifocal lenses]. / Individualisierte Presbyopiekorrektur bei der Kataraktoperation: Monovision und Multifokallinsen.

The cataract operation has transformed from a procedure for correcting spherical and astigmatic errors to one for correcting even presbyopia. Higher demands by the patients and more and more complex and individual lifestyle options need customised concepts of presbyopic correction, taking also into account comorbidities and neuroadaption. One concept for achieving this goal is multifocal lenses, undergoing a renaissance these days. Monovision using monofocal lenses is a cost neutral alternative with very few side effects, if well performed. It is defined by the far focus of one eye and the near focus of the other. Binocularity of human vision enables multiple options by combining different means of presbyopia correction. But it also complicates making the right choice. This underlines the importance of an accurate patient selection and the precise definition of what to achieve for each individual patient.

Closing the loop for Deep Brain Stimulation implants enables personalized healthcare for Parkinson's disease patients.

DEEP brain stimulation implants have improved life quality for more than 70,000 patients world-wide with diseases like Parkinson's, essential tremor, or obsessive-compulsive disorder where pharmaceutical therapies alone could not offer sufficient relief. Still, optimization and monitoring relies heavily on regular clinical visits, putting a burden on patient's comfort and clinicians. Permanent monitoring and combination with other patient health signals could ultimately lead to a personalized closed-loop therapy with remote quality monitoring. This requires technological improvements on the DBS implants such as integration of recording capabilities for brain activity monitoring, active low-power electronics, rechargeable battery technology, and body sensor networks for integration with e.g. gait, speech, and other vital information sensors on the patient's body and a link to a telemedicine platform using mobile technologies.

Biomarkers in the era of personalized medicine - a multiplexed SNP assay using capillary electrophoresis for assessing drug metabolism capacity.

Pharmacogenetics is the study of genetic differences in an individual that leads to variability in drug response. Single-nucleotide polymorphisms (SNPs) prove to be important determinants in evaluating and predicting a patient's response to certain medications and risk of adverse events. The Cytochrome P450 2D6 (CYP2D6) gene is particularly important in the metabolism of many clinically prescribed drugs. In this study, we designed a multiplexed panel to interrogate 8 clinically relevant SNPs of CYP2D6 (*2 at C2856G, *2 at G4181C, *3, *4, *5,*6, *7, and *8). We PCR-amplified a 4.7 kB segment of the CYP2D6 locus containing all the SNPs of interest using genomic DNA extracted from whole blood. Using single base extension and capillary electrophoresis separation, peaks corresponding to the SNPs resolve within a 25-60 bp window. We subsequently analyzed 25 samples using this protocol and compared results to traditional DNA sequencing using an ABI 3730. All samples were 100% concordant between the two methods. This assay can be performed with <24 h turnaround time and minimal hands-on effort. This multiplex SNP panel can be used for interrogation of 8 SNPs within the 2D6 gene, with application to identifying poor metabolizers of 2d6. Patients harbouring SNPs in 2D6 could be triaged to alternative therapies in an effort to maximize therapeutic efficacy and reduce adverse drug reactions.