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LoRa technology has gained popularity as one of the most widely used standards for device interconnection due to its ability to cover long distances and energy efficiency, making it a suitable choice for various Internet of Things (IoT) monitoring and control applications. In this sense, this work presents the development of a visual support tool for creating IoT devices with LoRa and LoRaWAN connectivity. This work significantly advances the state of the art in LoRa technology by introducing a novel visual support tool tailored for creating IoT devices with LoRa and LoRaWAN connectivity. By simplifying the development process and offering compatibility with multiple hardware solutions, this research not only facilitates the integration of LoRaWAN technology within educational settings but also paves the way for rapid prototyping of IoT nodes. The incorporation of block programming for LoRa and LoRaWAN using the Arduinoblocks framework as a graphical environment enhances the capabilities of the tool, positioning it as a comprehensive solution for efficient firmware generation. In addition to the visual tool for firmware generation, multiple compatible hardware solutions enable easy, economical, and stable development, offering a comprehensive hardware and software solution. The hardware proposal is based on an ESP32 microcontroller, known for its power and low cost, in conjunction with an RFM9x module that is based on SX127x LoRa transceivers. Finally, three successfully tested use cases and a discussion are presented.

The transfer from batch to flow chemistry is often based on commercial microfluidic equipment, such as costly complete reactor systems, which cannot be easily tailored to specific requirements of technologies such as DNA-encoded library technology (DELT), in particular for increasingly important photochemical reactions. Customized photoreactor concepts using rapid prototyping technology offer a modular, flexible, and affordable design that allows for adaptation to various applications. In order to validate the prototype reactors, a photochemical pinacol coupling reaction at 368 nm was conducted to demonstrate the transfer from batch to flow chemistry. The conversion rates were optimized by adapting the design parameters of the microfluidic flow photoreactor module. Subsequently, the photoreactor module has been extended to an application with DNA-tagged substrates by switching to LEDs with a wavelength of 454 nm. The successful recovery of DNA confirmed the feasibility of the modular-designed flow photo reactor. This collaborative approach holds enormous potential to drive the development of DELT and flow equipment design.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2023 Dinter, Willems, Nissalk, Hastürk, Brunschweiger and Kockmann.)

Humans, Models, Anatomic, Computer Simulation, Hand, Anastomosis, Surgical education, Clinical Competence, Thoracic Surgical Procedures, and Simulation Training

Objective: The objective of this paper is to describe the techniques and process of developing and testing a take-home surgical anastomosis simulation model.
Design: Through an iterative process, a simulation model was customized and designed to target specific skill development and performance objectives that focused on anastomotic techniques in thoracic surgery and consist of 3D printed and silicone molded components. Various manufacturing techniques such as silicone dip spin coating and injection molding have been described in this paper and explored as part of the research and development process. The final prototype is a low-cost, take-home model with reusable and replaceable components.
Setting: The study took place at a single-center quaternary care university-affiliated hospital.
Participants: The participants included in the model testing were 10 senior thoracic surgery trainees who completed an in-person training session held during an annual hands- on thoracic surgery simulation course. Feedback was then collected in the form of an evaluation of the model from participants.
Results: All 10 participants had an opportunity to test the model and complete at least 1 pulmonary artery and bronchial anastomosis. The overall experience was rated highly, with minor feedback provided regarding the set- up and fidelity of the materials used for the anastomoses. Overall, the trainees agreed that the model was suitable for teaching advanced anastomotic techniques and expressed an interest in being able to use this model to practice skill development.
Conclusions: Developed simulation model can be easily reduced, with customized components that accurately simulate real-life vascular and bronchial components suitable for training of anastomoses technique amongst senior thoracic surgery trainees.
(Copyright © 2023. Published by Elsevier Inc.)

Models of urea kinetics facilitate a mechanistic understanding of urea transfer and provide a tool for optimizing dialysis efficacy. Dual-compartment models have largely replaced single-compartment models as they are able to accommodate the urea rebound on the cessation of dialysis. Modeling the kinetics of urea and other molecular species is frequently regarded as a rarefied academic exercise with little relevance at the bedside. We demonstrate the utility of System Dynamics in creating multi-compartment models of urea kinetics by developing a dual-compartment model that is efficient, intuitive, and widely accessible to a range of practitioners. Notwithstanding its simplicity, we show that the System Dynamics model compares favorably with the performance of a more complex volume-average model in terms of calibration to clinical data and parameter estimation. Its intuitive nature, ease of development/modification, and excellent performance with real-world data may make System Dynamics an invaluable tool in widening the accessibility of hemodialysis modeling.
(© 2023. The Author(s).)

Optical sensing offers several advantages owing to its non-invasiveness and high sensitivity. The miniaturization of optical sensors will mitigate spatial and weight constraints, expanding their applications and extending the principal advantages of optical sensing to different fields, such as healthcare, Internet of Things, artificial intelligence, and other aspects of society. In this study, we present the development of a miniature optical sensor for monitoring thrombi in extracorporeal membrane oxygenation (ECMO). The sensor, based on a complementary metal-oxide semiconductor integrated circuit (CMOS-IC), also serves as a photodiode, amplifier, and light-emitting diode (LED)-mounting substrate. It is sized 3.8 × 4.8 × 0.75 mm 3 and provides reflectance spectroscopy at three wavelengths. Based on semiconductor and microelectromechanical system (MEMS) processes, the design of the sensor achieves ultra-compact millimeter size, customizability, prototyping, and scalability for mass production, facilitating the development of miniature optical sensors for a variety of applications.

Since temperature and its spatial, and temporal variations affect a wide range of physical properties of material systems, they can be used to create reconfigurable spatial structures of various types in physical and biological objects. This paper presents an experimental optical setup for creating tunable two-dimensional temperature patterns on a micrometer scale. As an example of its practical application, we have produced temperature-induced magnetization landscapes in ferrimagnetic yttrium iron garnet films and investigated them using micro-focused Brillouin light scattering spectroscopy. It is shown that, due to the temperature dependence of the magnon spectrum, spatial temperature distributions can be visualized even for microscale thermal patterns.
(© 2023 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).)

Animals, Antivenins therapeutic use, Antibodies, Monoclonal therapeutic use, Snake Bites diagnosis, Snake Bites drug therapy, Crotalid Venoms therapeutic use, and Bothrops

Background: Brazil is home to a multitude of venomous snakes; perhaps the most medically relevant of which belong to the Bothrops genus. Bothrops spp. are responsible for roughly 70% of all snakebites in Brazil, and envenomings caused by their bites can be treated with three types of antivenom: bothropic antivenom, bothro-lachetic antivenom, and bothro-crotalic antivenom. The choice to administer antivenom depends on the severity of the envenoming, while the choice of antivenom depends on availability and on how certain the treating physician is that the patient was bitten by a bothropic snake. The diagnosis of a bothropic envenoming can be made based on expert identification of the dead snake or a photo thereof or based on a syndromic approach wherein the clinician examines the patient for characteristic manifestations of envenoming. This approach can be very effective but requires staff that has been trained in clinical snakebite management, which, unfortunately, far from all relevant staff has.
Results: In this article, we describe a prototype of the first lateral flow assay (LFA) capable of detecting venoms from Brazilian Bothrops spp. The monoclonal antibodies for the assay were generated using hybridoma technology and screened in sandwich enzyme-linked immunosorbent assays (ELISAs) to identify Bothrops spp.-specific antibody sandwich pairs. The prototype LFA is able to detect venom from several Bothrops spp. The LFA has a limit of detection (LoD) of 9.5 ng/mL in urine, when read with a commercial reader, and a visual LoD of approximately 25 ng/mL.
Significance: The work presented here serves as a proof of concept for a genus-specific venom detection kit that could support physicians in diagnosing Bothrops envenomings. Although further optimisation and testing is needed before the LFA can find clinical use, such a device could aid in decentralising antivenoms in the Brazilian Amazon and help ensure optimal snakebite management for even more victims of this highly neglected disease.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Cecilie Knudsen, Jonas A. Jürgensen, Søren H. Dam, Aleksander M. Haack, Rasmus U. W. Friis, and Andreas H. Laustsen are co-founders of VenomAid Diagnostics A/S. Jonas A. Jürgensen, Pelle D. Knudsen, and Georgina M. Ross are employed by VenomAid Diagnostics A/S. Cecilie Knudsen is an industrial PhD student at the Technical University of Denmark. Her PhD is co-sponsored by Innovation Fund Denmark and BioPorto Diagnostics A/S. Cecilie Knudsen, Jonas A. Jürgensen, Søren H. Dam, Aleksander M. Haack, Rasmus U. W. Friis, and Andreas H. Laustsen have been designated as inventors on a patent application related to the work presented here.
(Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Humans, Prospective Studies, Fatigue, Educational Status, Psychiatry, and Military Personnel

Background: Military service inherently includes frequent periods of high-stress training, operational tempo, and sustained deployments to austere far-forward environments. These occupational requirements can contribute to acute and chronic sleep disruption, fatigue, and behavioral health challenges related to acute and chronic stress and disruption of team dynamics. To date, there is no centralized mobile health platform that supports self- and supervised detection, monitoring, and management of sleep and behavioral health issues in garrison and during and after deployments.
Objective: The objective of this study was to adapt a clinical decision support platform for use outside clinical settings, in garrison, and during field exercises by medics and soldiers to monitor and manage sleep and behavioral health in operational settings.
Methods: To adapt an existing clinical decision support digital health platform, we first gathered system, content, and context-related requirements for a sleep and behavioral health management system from experts. Sleep and behavioral health assessments were then adapted for prospective digital data capture. Evidence-based and operationally relevant educational and interventional modules were formatted for digital delivery. These modules addressed the management and mitigation of sleep, circadian challenges, fatigue, stress responses, and team communication. Connectivity protocols were adapted to accommodate the absence of cellular or Wi-Fi access in deployed settings. The resulting apps were then tested in garrison and during 2 separate field exercises.
Results: Based on identified requirements, 2 Android smartphone apps were adapted for self-monitoring and management for soldiers (Soldier app) and team supervision and intervention by medics (Medic app). A total of 246 soldiers, including 28 medics, received training on how to use the apps. Both apps function as expected under conditions of limited connectivity during field exercises. Areas for future technology enhancement were also identified.
Conclusions: We demonstrated the feasibility of adapting a clinical decision support platform into Android smartphone-based apps to collect, save, and synthesize sleep and behavioral health data, as well as share data using adaptive data transfer protocols when Wi-Fi or cellular data are unavailable. The AIRE (Autonomous Connectivity Independent System for Remote Environments) prototype offers a novel self-management and supervised tool to augment capabilities for prospective monitoring, detection, and intervention for emerging sleep, fatigue, and behavioral health issues that are common in military and nonmilitary high-tempo occupations (eg, submarines, long-haul flights, space stations, and oil rigs) where medical expertise is limited.
(©Anne Germain, Megan Wolfson, I Wayan Pulantara, Meredith L Wallace, Katie Nugent, George Mesias, Kristina Clarke-Walper, Phillip J Quartana, Joshua Wilk. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 28.08.2023.)

Lab-On-A-Chip Devices, Microfluidics, and Nucleic Acid Amplification Techniques methods

In this work, we demonstrate an inexpensive method of prototyping microfluidics using a desktop injection molding machine. A centrifugal microfluidic device with a novel central filling mechanism was developed to demonstrate the technique. We overcame the limitations of desktop machines in replicating microfluidic features by variotherm heating and cooling the mold between 50 °C and 110 °C within two minutes. Variotherm heating enabled good replication of microfeatures, with a coefficient of variation averaging only 3.6% attained for the measured widths of 100 μm wide molded channels. Using this methodology, we produced functional polystyrene centrifugal microfluidic chips, capable of aliquoting fluids into 5.0 μL reaction chambers with 97.5% accuracy. We performed allele-specific loop-mediated isothermal amplification (AS-LAMP) reactions for genotyping CYP2C19 alleles on these chips. Readouts were generated using optical pH sensors integrated onto chips, by drop-casting sensor precursor solutions into reaction chambers before final chip assembly. Positive reactions could be discerned by decreases in pH sensor fluorescence, thresholded against negative control reactions lacking the primers for nucleic acid amplification and with time-to-results averaging 38 minutes. Variotherm desktop injection molding can enable researchers to prototype microfluidic devices more cost-effectively, in an iterative fashion, due to reduced costs of smaller, in-house molds. Designs prototyped this way can be directly translated to mass production, enhancing their commercialization potential and positive impacts.

Three-dimensional printing technology has been used for more than three decades in many industries, including the automotive and aerospace industries. So far, the use of this technology in medicine has been limited only to 3D printing of anatomical models for educational and training purposes, which is due to the insufficient functional properties of the materials used in the process. Only recent advances in the development of innovative materials have resulted in the flourishing of the use of 3D printing in medicine and pharmacy. Currently, additive manufacturing technology is widely used in clinical fields. Rapid development can be observed in the design of implants and prostheses, the creation of biomedical models tailored to the needs of the patient and the bioprinting of tissues and living scaffolds for regenerative medicine. The purpose of this review is to characterize the most popular 3D printing techniques.

The increasing demand for seafood is responsible for many environmental impacts, especially caused by aquaculture. Shrimp accounts for a substantial part of seafood production and therefore also for negative effects associated with it. This work aimed to develop a mushroom-based shrimp analogue with a texture similar to shrimp using the fruiting bodies of pink oyster mushroom ( Pleurotus djamor ) and lion's mane ( Hericium erinaceus ). Three flushes of pink oyster mushrooms and a first flush of lion's mane mushroom were analysed regarding their nutritional composition and whether they are suitable shrimp alternatives. The two mushrooms are rich in proteins (∼32% and ∼26% w/w for the first flush of pink oyster and lion's mane, respectively). The protein content of pink oyster mushroom decreased and the dietary fibre content increased across the different flushes. The antioxidants in the mushrooms were extracted using different methods, whereby aqueous extracts mostly excelled in terms of antioxidant activity. Hydrolysis confirmed the presence of conjugated p -coumaric acid in both mushrooms and possibly conjugated caffeic acid in pink oyster. Texture analysis results of the prototypes were close to the values of fried shrimp. However, although the sensory qualities of the final prototypes were perceived as similar to shrimp, further improvements in the recipe are necessary to make the prototypes indistinguishable from shrimp.
Competing Interests: None.
(© 2023 The Author(s).)

This study proposes a design approach and the development of a low-power planar biped robot named YU-Bibot. The kinematic structure of the robot consists of six independently driven axes, and it weighs approximately 20 kg. Based on biomimetics, the robot dimensions were selected as the average anthropomorphic dimensions of the human lower extremities. The optimization of the mechanical design and actuator selection of the robot was based on the results of parametric simulations. The natural human walking gait was mimicked as a walking pattern in these simulations. As a result of the optimization, a low power-to-weight ratio of 30 W/kg was obtained. The drive system of the robot joints consists of servo-controlled brushless DC motors with reduction gears and additional bevel gears at the knee and ankle joints. The robot features spring-supported knee and ankle joints that counteract the robot's weight and compensate for the backlash present in these joints. The robot is constrained to move only in the sagittal plane by using a lateral support structure. The robot's feet are equipped with low-cost, force-sensitive resistor (FSR)-type sensors for monitoring ground contact and zero-moment point (ZMP) criterion. The experimental results indicate that the proposed robot mechanism can follow the posture commands accurately and demonstrate locomotion at moderate stability. The proposed parametric natural gait simulation-based design approach and the resulting biped robot design with a low power/weight ratio are the main contributions of this study.

Microfluidic devices have found extensive applications in mechanical, biomedical, chemical, and materials research. However, the high initial cost, low resolution, inferior feature fidelity, poor repeatability, rough surface finish, and long turn-around time of traditional prototyping methods limit their wider adoption. In this study, a strategic approach to a deterministic fabrication process based on in-situ image analysis and intermittent flow control called image-guided in-situ maskless lithography (IGIs-ML), has been proposed to overcome these challenges. By using dynamic image analysis and integrated flow control, IGIs-ML provides superior repeatability and fidelity of densely packed features across a large area and multiple devices. This general and robust approach enables the fabrication of a wide variety of microfluidic devices and resolves critical proximity effect and size limitations in rapid prototyping. The affordability and reliability of IGIs-ML make it a powerful tool for exploring the design space beyond the capabilities of traditional rapid prototyping.
(© 2023. The Author(s).)

In this work, we introduce a polymer version of a previously developed silicon MEMS drop deposition tool for surface functionalization that consists of a microcantilever integrating an open fluidic channel and a reservoir. The device is fabricated by laser stereolithography, which offers the advantages of low-cost and fast prototyping. Additionally, thanks to the ability to process multiple materials, a magnetic base is incorporated into the cantilever for convenient handling and attachment to the holder of a robotized stage used for spotting. Droplets with diameters ranging from ∼50 µm to ∼300 µm are printed upon direct contact of the cantilever tip with the surface to pattern. Liquid loading is achieved by fully immersing the cantilever into a reservoir drop, where a single load results in the deposition of more than 200 droplets. The influences of the size and shape of the cantilever tip and the reservoir on the printing outcome are studied. As a proof-of-concept of the biofunctionalization capability of this 3D printed droplet dispenser, microarrays of oligonucleotides and antibodies displaying high specificity and no cross-contamination are fabricated, and droplets are deposited at the tip of an optical fiber bundle.
Competing Interests: Conflict of interestThe authors declare no competing interests.
(© The Author(s) 2023.)

Animals, Bayes Theorem, Uncertainty, and Anthozoa

Emerging diseases can have devastating consequences for wildlife and require a rapid response. A critical first step towards developing appropriate management is identifying the etiology of the disease, which can be difficult to determine, particularly early in emergence. Gathering and synthesizing existing information about potential disease causes, by leveraging expert knowledge or relevant existing studies, provides a principled approach to quickly inform decision-making and management efforts. Additionally, updating the current state of knowledge as more information becomes available over time can reduce scientific uncertainty and lead to substantial improvement in the decision-making process and the application of management actions that incorporate and adapt to newly acquired scientific understanding. Here we present a rapid prototyping method for quantifying belief weights for competing hypotheses about the etiology of disease using a combination of formal expert elicitation and Bayesian hierarchical modeling. We illustrate the application of this approach for investigating the etiology of stony coral tissue loss disease (SCTLD) and discuss the opportunities and challenges of this approach for addressing emergent diseases. Lastly, we detail how our work may apply to other pressing management or conservation problems that require quick responses. We found the rapid prototyping methods to be an efficient and rapid means to narrow down the number of potential hypotheses, synthesize current understanding, and help prioritize future studies and experiments. This approach is rapid by providing a snapshot assessment of the current state of knowledge. It can also be updated periodically (e.g., annually) to assess changes in belief weights over time as scientific understanding increases. Synthesis and applications: The rapid prototyping approaches demonstrated here can be used to combine knowledge from multiple experts and/or studies to help with fast decision-making needed for urgent conservation issues including emerging diseases and other management problems that require rapid responses. These approaches can also be used to adjust belief weights over time as studies and expert knowledge accumulate and can be a helpful tool for adapting management decisions.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier Ltd. All rights reserved.)

Female, Humans, Pilot Projects, Endoscopes, Fallopian Tubes, Ovarian Neoplasms diagnostic imaging, and Ovarian Neoplasms pathology

Significance: High grade serous ovarian cancer is the most deadly gynecological cancer, and it is now believed that most cases originate in the fallopian tubes (FTs). Early detection of ovarian cancer could double the 5-year survival rate compared with late-stage diagnosis. Autofluorescence imaging can detect serous-origin precancerous and cancerous lesions in ex vivo FT and ovaries with good sensitivity and specificity. Multispectral fluorescence imaging (MFI) can differentiate healthy, benign, and malignant ovarian and FT tissues. Optical coherence tomography (OCT) reveals subsurface microstructural information and can distinguish normal and cancerous structure in ovaries and FTs.
Aim: We developed an FT endoscope, the falloposcope, as a method for detecting ovarian cancer with MFI and OCT. The falloposcope clinical prototype was tested in a pilot study with 12 volunteers to date to evaluate the safety and feasibility of FT imaging prior to standard of care salpingectomy in normal-risk volunteers. In this manuscript, we describe the multiple modifications made to the falloposcope to enhance robustness, usability, and image quality based on lessons learned in the clinical setting.
Approach: The ∼ 0.8    mm diameter falloposcope was introduced via a minimally invasive approach through a commercially available hysteroscope and introducing a catheter. A navigation video, MFI, and OCT of human FTs were obtained. Feedback from stakeholders on image quality and procedural difficulty was obtained.
Results: The falloposcope successfully obtained images in vivo . Considerable feedback was obtained, motivating iterative improvements, including accommodating the operating room environment, modifying the hysteroscope accessories, decreasing endoscope fragility and fiber breaks, optimizing software, improving fiber bundle images, decreasing gradient-index lens stray light, optimizing the proximal imaging system, and improving the illumination.
Conclusions: The initial clinical prototype falloposcope was able to image the FTs, and iterative prototyping has increased its robustness, functionality, and ease of use for future trials.
(© 2023 The Authors.)

Background: Design dynamics that evolve during a designer's prototyping process encapsulate important insights about the way the designer is using his or her knowledge, creativity, and reflective thinking. Nevertheless, the capturing of such dynamics is not always an easy task, as they are built through alternations between the self-first and self-third person views.
Objective: This study aimed at introducing a conceptual framework, namely 2D-ME, to provide an explainable domain that could express the dynamics across the design timeline during a prototyping process of serious games.
Methods: Within the 2D-ME framework, the Technological-Pedagogical-Content Knowledge (TPACK), its adaptation to the serious games (TPACK-Game), and the activity theory frameworks were combined to produce dynamic constructs that incorporate self-first and self-third person extension of the TPACK-Game to Games TPACK, rules, division of labor, and object. The dynamic interplay between such constructs was used as an adaptation engine within an optimization prototype process, so each sequential version of the latter could converge to the designer's initial idea of the serious game. Moreover, higher-order thinking is scaffolded with the internal Activity Interview Script proposed in this paper.
Results: An experimental case study of the application of the 2D-ME conceptual framework in the design of a light reflection game was showcased, revealing all the designer's dynamics, both from internal (via a diary) and external (via the prototype version) views. The findings of this case study exemplified the convergence of the prototyping process to an optimized output, by minimizing the mean square error between the conceptual (initial and updated) idea of the prototype, following explainable and tangible constructs within the 2D-ME framework.
Conclusions: The generic structure of the proposed 2D-ME framework allows its transferability to various levels of expertise in serious games mastering, and it is used both for the designer's process exploration and training of the novice ones.
(©Sofia Hadjileontiadou, Sofia B Dias, Leontios Hadjileontiadis. Originally published in JMIR Serious Games (https://games.jmir.org), 24.04.2023.)

Green Fluorescent Proteins chemistry, Green Fluorescent Proteins genetics, Biosynthetic Pathways, Metabolic Engineering methods, Nicotinamide Mononucleotide biosynthesis, Enzymes chemistry, and Enzymes genetics

Engineering biological systems to test new pathway variants containing different enzyme homologs is laborious and time-consuming. To tackle this challenge, a strategy was developed for rapidly prototyping enzyme homologs by combining cell-free protein synthesis (CFPS) with split green fluorescent protein (GFP). This strategy featured two main advantages: (1) dozens of enzyme homologs were parallelly produced by CFPS within hours, and (2) the expression level and activity of each homolog was determined simultaneously by using the split GFP assay. As a model, this strategy was applied to optimize a 3-step pathway for nicotinamide mononucleotide (NMN) synthesis. Ten enzyme homologs from different organisms were selected for each step. Here, the most productive homolog of each step was identified within 24 h rather than weeks or months. Finally, the titer of NMN was increased to 1213 mg/L by improving physiochemical conditions, tuning enzyme ratios and cofactor concentrations, and decreasing the feedback inhibition, which was a more than 12-fold improvement over the initial setup. This strategy would provide a promising way to accelerate design-build-test cycles for metabolic engineering to improve the production of desired products.
(© 2023 Wiley Periodicals LLC.)

Two antimicrobial agents such as silver nanoparticles (AgNPs) and titanium dioxide (TiO 2 ) have been formulated with natural polysaccharides (chitosan or alginate) to develop innovative inks for the rapid, customizable, and extremely accurate manufacturing of 3D-printed scaffolds useful as dressings in the treatment of infected skin wounds. Suitable chemical-physical properties for the applicability of these innovative devices were demonstrated through the evaluation of water content (88-93%), mechanical strength (Young's modulus 0.23-0.6 MPa), elasticity, and morphology. The antimicrobial tests performed against Staphylococcus aureus and Pseudomonas aeruginosa demonstrated the antimicrobial activities against Gram+ and Gram- bacteria of AgNPs and TiO 2 agents embedded in the chitosan (CH) or alginate (ALG) macroporous 3D hydrogels (AgNPs MIC starting from 5 µg/mL). The biocompatibility of chitosan was widely demonstrated using cell viability tests and was higher than that observed for alginate. Constructs containing AgNPs at 10 µg/mL concentration level did not significantly alter cell viability as well as the presence of titanium dioxide; cytotoxicity towards human fibroblasts was observed starting with an AgNPs concentration of 100 µg/mL. In conclusions, the 3D-printed dressings developed here are cheap, highly defined, easy to manufacture and further apply in personalized antimicrobial medicine applications.

This study aims to describe the prototype development and testing of a serious game designed for Brazilian children with diabetes. Following an approach of user-centered design, the researchers assessed game's preferences and diabetes learning needs to develop a Paper Prototype. The gameplay strategies included diabetes pathophysiology, self-care tasks, glycemic management, and food group learning. Diabetes and technology experts (n = 12) tested the prototype during audio-recorded sessions. Next, they answered a survey to evaluate the content, organization, presentation, and educational game aspects. The prototype showed a high content validity ratio (0.80), with three items not achieving the critical values (0.66). Experts recommended improving the game content and food illustrations. This evaluation contributed to the medium-fidelity prototype version, which after testing with diabetes experts (n = 12) achieved high content validity values (0.88). One item did not meet the critical values. Experts suggested increasing the options of outdoor activities and meals. Researchers also observed and video-recorded children with diabetes (n = 5) playing the game with satisfactory interaction. They considered the game enjoyable. The interdisciplinary team plays an important role guiding the designers in the use of theories and real needs of children. Prototypes are a low-cost usability and a successful method for evaluating games.
(Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Biotechnology, Microtechnology, Printing, Three-Dimensional, Microfluidics methods, and Cell Culture Techniques

Rapid prototyping of microfluidic chips is a key enabler for controlled biotechnology applications in microspaces, as it allows for the efficient design and production of microfluidic systems. With rapid prototyping, researchers and engineers can quickly create and test new microfluidic chip designs, which can then be optimized for specific applications in biotechnology. One of the key advantages of microfluidic chips for biotechnology is the ability to manipulate and control biological samples in a microspace, which enables precise and controlled experiments under well-defined conditions. This is particularly useful for applications such as cell culture, drug discovery, and diagnostic assays, where precise control over the biological environment is crucial for obtaining accurate results. Established methods, for example, soft lithography, 3D printing, injection molding, as well as other recently highlighted innovative approaches, will be compared and challenges as well as limitations will be discussed. It will be shown that rapid prototyping of microfluidic chips enables the use of advanced materials and technologies, such as smart materials and digital sensors, which can further enhance the capabilities of microfluidic systems for biotechnology applications. Overall, rapid prototyping of microfluidic chips is an important enabling technology for controlled biotechnology applications in microspaces, as well as for upscaling it into macroscopic bioreactors, and its continued development and improvement will play a critical role in advancing the field. The review will highlight recent trends in terms of materials and competing approaches and shed light on current challenges on the way toward integrated microtechnologies. Also, the possibility to easy and direct implementation of novel functions (membranes, functionalization of interfaces, etc.) is discussed.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier Ltd. All rights reserved.)

Three-dimensional (3D) printing technology is advantageous in the fast prototyping of complex structures, but its utilization in functional material fabrication is still limited due to a lack of activation capability. To fabricate and activate the functional material of electrets, a synchronized 3D printing and corona charging method is presented to prototype and polarize polylactic acid electrets in one step. By upgrading the 3D printer nozzle and incorporating a needle electrode to apply high voltage, parameters such as needle tip distance and applied voltage level were compared and optimized. Under different experimental conditions, the average surface distribution in the center of the samples was -1498.87 V, -1115.73 V, and -814.51 V. Scanning electron microscopy results showed that the electric field contributes to keeping the printed fiber structure straight. The polylactic acid electrets exhibited relatively uniform surface potential distribution on a sufficiently large sample surface. In addition, the average surface potential retention rate was improved by 12.021-fold compared to ordinary corona-charged samples. The above advantages are unique to the 3D-printed and polarized polylactic acid electrets, proving that the proposed method is suitable for quickly prototyping and effectively polarizing the polylactic acid electrets simultaneously.

Female, Humans, Spectroscopy, Fourier Transform Infrared, Fluorouracil, Polyesters, and Uterine Cervical Neoplasms drug therapy

Solid lipid nanoparticles (SLNs) are used extensively to achieve site-specific drug delivery with improved bioavailability and reduced toxicity. This work focused on a new approach to provide site-specific stimuli-responsive delivery of SLNs loaded within thermo-sonic nano-organogel (TNO) variants to deliver the model chemotherapeutic agent 5-FU in treating cervical cancer. Pharmaceutically stable nanospherical SLNs comprising poly-L-lactic acid (PLA), palmitic acid (PA), and polyvinyl alcohol (PVA) were prepared and incorporated into TNO variants augmented by external thermal and ultrasound stimuli for release of 5-FU in the cervix. Results revealed that rate-modulated 5-FU release was achieved from SLNs (particle size =450.9 nm; PDI =0.541; zeta potential =-23.2 mV; %DL =33%) within an organogel upon exposure to either a single (thermo-) and/or both (thermo-sonic) stimuli. 5FU was released from all TNO variants with an initial burst on day 1 followed by sustained release over 14 days. TNO 1 provided desirable release over 15 days (44.29% vs. 67.13% under single (T) or combined (TU) stimuli, respectively). Release rates were primarily influenced by the SLN:TO ratio in tandem with biodegradation and hydrodynamic influx. Biodegradation by day 7 revealed that variant TNO 1 (1:5) released 5FU (46.8%) analogous to its initial mass than the other TNO variants (i.e., ratios of 2:5 and 3:5). FT-IR spectra revealed assimilation of the system components and corroborative with the DSC and XRD analysis (i.e., in ratios of PA:PLA 1:1 and 2:1). In conclusion, the TNO variants produced may be used as a potential stimuli-responsive platform for the site-specific delivery of chemotherapeutic agents such as 5-FU to treat cervical cancer.
(© 2023. The Author(s).)

Humans, Porosity, Electrodes, and Graphite

Flexible pressure sensors are widely applied in tactile perception, fingerprint recognition, medical monitoring, human-machine interfaces, and the Internet of Things. Among them, flexible capacitive pressure sensors have the advantages of low energy consumption, slight signal drift, and high response repeatability. However, current research on flexible capacitive pressure sensors focuses on optimizing the dielectric layer for improved sensitivity and pressure response range. Moreover, complicated and time-consuming fabrication methods are commonly applied to generate microstructure dielectric layers. Here, we propose a rapid and straightforward fabrication approach to prototyping flexible capacitive pressure sensors based on porous electrodes. Laser-induced graphene (LIG) is produced on both sides of the polyimide paper, resulting in paired compressible electrodes with 3D porous structures. When the elastic LIG electrodes are compressed, the effective electrode area, the relative distance between electrodes, and the dielectric property vary accordingly, thereby generating a sensitive pressure sensor in a relatively large working range (0-9.6 kPa). The sensitivity of the sensor is up to 7.71%/kPa -1 , and it can detect pressure as small as 10 Pa. The simple and robust structure allows the sensor to produce quick and repeatable responses. Our pressure sensor exhibits broad potential in practical applications in health monitoring, given its outstanding comprehensive performance combined with its simple and quick fabrication method.

Because they are made of elastically deformable and compliant materials, soft robots can passively change shape and conform to their environment, providing potential advantages over traditional robotics approaches. However, existing manufacturing workflows are often labor intensive and limited in their ability to create highly integrated three-dimensional (3D) heterogeneous material systems. In this study, we address this with a streamlined workflow to produce field-deployable soft robots based on 3D printing with digital light processing (DLP) of silicone-like soft materials. DLP-based 3D printing is used to create soft actuators (2.2 g) capable of exerting up to 0.5 Newtons of force that are integrated into a bioinspired untethered soft robot. The robot walks underwater at speeds comparable with its biological analog, the brittle star. Using a model-free planning algorithm and feedback, the robot follows remote commands to move to desired positions. Moreover, we show that the robot is able to perform untethered locomotion outside of a laboratory and in a natural aquatic environment. Our results represent progress in soft robot manufacturing autonomy for a 3D printed untethered soft robot.

Lab-On-A-Chip Devices, Polymers, Dimethylpolysiloxanes, and Microtechnology

Polydimethylsiloxane (PDMS) based microfluidic devices have found increasing utility for electrophoretic and electrokinetic assays because of their ease of fabrication using replica molding. However, the fabrication of high-resolution molds for replica molding still requires the resource-intensive and time-consuming photolithography process, which precludes quick design iterations and device optimization. We here demonstrate a low-cost, rapid microfabrication process, based on electrohydrodynamic jet printing (EJP), for fabricating non-sacrificial master molds for replica molding of PDMS microfluidic devices. The method is based on the precise deposition of an electrically stretched polymeric solution of polycaprolactone in acetic acid on a silicon wafer placed on a computer-controlled motion stage. This process offers the high-resolution (order 10  μ $\umu$ m) capability of photolithography and rapid prototyping capability of inkjet printing to print high-resolution templates for elastomeric microfluidic devices within a few minutes. Through proper selection of the operating parameters such as solution flow rate, applied electric field, and stage speed, we demonstrate microfabrication of intricate master molds and corresponding PDMS microfluidic devices for electrokinetic applications. We demonstrate the utility of the fabricated PDMS microchips for nonlinear electrokinetic processes such as electrokinetic instability and controlled sample splitting in ITP. The ability to rapid prototype customized reusable master molds with order 10  μ $\umu$ m resolution within a few minutes can help in designing and optimizing microfluidic devices for various electrokinetic applications.
(© 2023 Wiley-VCH GmbH.)

A flexible power electronic converter embedding a rapid control prototyping platform suitable to be applied in research test setups and teaching laboratories is proposed and described in this paper. The electronic system is composed of three subsystems, namely, i ) three half-bridge power boards, ii ) a dc-link capacitor bank with a half-bridge power module for active dc-link control, iii ) an interfacing board, called motherboard, to couple the power modules with a control unit, iv ) a digital control unit with rapid control prototyping functionalities for controlling power electronic circuits. Power modules integrate sensors with related conditioning circuits, driving circuits for power switches, and protection circuits. Conversion circuits exploit GaN electronic switches for optimal performance. The architecture and implementation of the system are described in detail in this manuscript. Main applications are in the implementation of conversion circuits for supplying arbitrary ac or dc voltages or currents, testing of new control algorithms for power electronic converters, testing of systems of electronic converters in, for example, smart nanogrids or renewable energy applications, training of undergraduate and graduate students.
Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(© 2023 The Author(s).)

This study presents a robustness optimization method for rapid prototyping (RP) of functional artifacts based on visualized computing digital twins (VCDT). A generalized multiobjective robustness optimization model for RP of scheme design prototype was first built, where thermal, structural, and multidisciplinary knowledge could be integrated for visualization. To implement visualized computing, the membership function of fuzzy decision-making was optimized using a genetic algorithm. Transient thermodynamic, structural statics, and flow field analyses were conducted, especially for glass fiber composite materials, which have the characteristics of high strength, corrosion resistance, temperature resistance, dimensional stability, and electrical insulation. An electrothermal experiment was performed by measuring the temperature and changes in temperature during RP. Infrared thermographs were obtained using thermal field measurements to determine the temperature distribution. A numerical analysis of a lightweight ribbed ergonomic artifact is presented to illustrate the VCDT. Moreover, manufacturability was verified based on a thermal-solid coupled finite element analysis. The physical experiment and practice proved that the proposed VCDT provided a robust design paradigm for a layered RP between the steady balance of electrothermal regulation and manufacturing efficacy under hybrid uncertainties.
(© 2023. The Author(s).)

Hydrodynamics, Kinetics, Ultraviolet Rays, Disinfection methods, and Water Purification methods

We developed and studied one of the first high-flow UV-LED water disinfection reactors applicable to point-of-entry (POE) water disinfection. A multiphysics computational model was created to predict the performance of UV reactor design concepts by modeling the synergic effect of radiation, hydrodynamics, and the inactivation kinetics of microorganisms. The geometrical optics that describe light propagation in terms of rays were employed to model the radiation profile of multiple UV-LEDs with optical components in complex reactor geometries, the first account of such an approach. The computational solution of the mass, momentum, and species equations was applied to model the hydrodynamics and kinetics. We designed a reactor through a detailed computational study of the optical and hydrodynamic performance of various design strategies. Highly efficient UV fluence distribution in the reactor was achieved by creating nearly collimated UV radiation beams across the reactor and managing the hydrodynamics using a flow distributor. We fabricated a prototype of the optimized reactor design for experimental studies. Biodosimetry tests were conducted for various flow rates and UV transmittances (UVTs), and the experimental results were compared with the model predictions. The design, which employed 14 UV-LEDs assembled over custom-made optical modules, resulted in a reduction equivalent dose (RED) of 65 mJ/cm 2 at a flow rate of 20 liters per minute (LPM) while consuming about 50 W energy. This reactor design required only 0.05 W radiant power per LPM flow rate to achieve an NSF Class A UV dose equivalent of 40 mJ/cm 2 . The findings of this study provide insights into UV-LED reactor development strategies as well as the creation and application of reactor virtual prototyping tools for designing and optimizing highly efficient UV-LED reactors.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023. Published by Elsevier Ltd.)

Following COVID-19, the global educational landscape shifted dramatically. Almost every educational institute in Bangladesh undertook a strategic move to begin offering online or blended learning courses to mitigate the challenges created by the pandemic. The TVET sector, particularly the polytechnic institute of Bangladesh, endeavored to explore the blended learning approach as an immediate and long-term solution to address the educational dislocation caused by the pandemic. This study attempts to conceptualize a pedagogical design based on the ADDIE and rapid prototyping model to make a reliable and robust instructional design to be used in the blended learning context. A content validity index (CVI) was used to validate the proposed model; a technology acceptance model (TAM) was employed to examine its acceptability to students; and finally, students' academic performances were analysed to evaluate the overall performance of the proposed instructional design. The findings reveal that the proposed instructional design can be a reliable and valid pedagogical approach to be implemented in the blended learning context for polytechnic students. The proposed instructional design may help TVET educators and course designers to create a robust blended learning environment in the TVET sector and in other similar disciplines, such as science and engineering education.
Competing Interests: Conflict of interestThe authors declare no competing interests.
(© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

As part of this work, polymer composites based on polycarbonate/acrylonitrile-butadiene-styrene (PC/ABS) were obtained and used in 3D printing technology, particularly Melted Extrusion Modeling (MEM) technology. The influence of selected fillers on the properties of the obtained composites was investigated. For this purpose, modified fillers such as silica modified with alumina, bentonite modified with a quaternary ammonium salt, and hybrid lignin/silicon dioxide filler were introduced into the PC/ABS matrix. In the first part of this work, polymer blends and their composites containing 1.5-3 wt. of the filler were used to obtain the filament using the proprietary technological line. Moldings for testing the performance properties were obtained using additive manufacturing techniques and injection molding. In the subsequent part of this work, rheological properties (mass flow rate (MFR) and viscosity curves) and mechanical properties (Rockwell hardness and static tensile strength with Young's modulus) were examined. The structures of the obtained composites were also determined by scanning electron microscopy (SEM/EDS). The obtained results confirmed the results obtained from a wide-angle X-ray scattering analysis (WAXS). In turn, the physicochemical properties were characterized on the basis of the results of tests using thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). Based on the obtained results, it was found that the introduced modified additives had a significant impact on the processing and functional properties of the tested composites.

In this paper, we report a simple, rapid, low-cost, biocompatible, and detachable microfluidic chip fabrication method for customized designs based on Parafilm ® . Here, Parafilm ® works as both a bonding agent and a functional membrane. Its high ultimate tensile stress (3.94 MPa) allows the demonstration of high-performance actuators such as microvalves and micropumps. By laser ablation and the one-step bonding of multiple layers, 3D structured microfluidic chips were successfully fabricated within 2 h. The consumption time of this method (~2 h) was 12 times less than conventional photolithography (~24 h). Moreover, the shear stress of the PMMA-Parafilm ® -PMMA specimens (0.24 MPa) was 2.13 times higher than that of the PDMS-PDMS specimens (0.08 MPa), and 0.56 times higher than that of the PDMS-Glass specimens (0.16 MPa), showing better stability and reliability. In this method, multiple easily accessible materials such as polymethylmethacrylate (PMMA), PVC, and glass slides were demonstrated and well-incorporated as our substrates. Practical actuation devices that required high bonding strength including microvalves and micropumps were fabricated by this method with high performance. Moreover, the biocompatibility of the Parafilm ® -based microfluidic devices was validated through a seven-day E. coli cultivation. This reported fabrication scheme will provide a versatile platform for biochemical applications and point-of-care diagnostics.

Background: Shoulder dislocations are common occurrences, yet there are few simulation devices to train medical personnel on how to reduce these dislocations. Reductions require a familiarity with the shoulder and a nuanced motion against strong muscle tension. The goal of this work is to describe the design of an easily replicated, low-cost simulator for training shoulder reductions.
Materials and Methods: An iterative, stepwise engineering design process was used to design and implement ReducTrain. A needs analysis with clinical experts led to the selection of the traction-countertraction and external rotation methods as educationally relevant techniques to include. A set of design requirements and acceptance criteria was established that considered durability, assembly time, and cost. An iterative prototyping development process was used to meet the acceptance criteria. Testing protocols for each design requirement are also presented. Step-by-step instructions are provided to allow the replication of ReducTrain from easily sourced materials, including plywood, resistance bands, dowels, and various fasteners, as well as a 3D-printed shoulder model, whose printable file is included at a link in the Additional file 1: Appendix.
Results: A description of the final model is given. The total cost for all materials for one ReducTrain model is under US $200, and it takes about 3 h and 20 min to assemble. Based on repetitive testing, the device should not see any noticeable changes in durability after 1000 uses but may exhibit some changes in resistance band strength after 2000 uses.
Discussion: The ReducTrain device fills a gap in emergency medicine and orthopedic simulation. Its wide variety of uses points to its utility in several instructional formats. With the rise of makerspaces and public workshops, the construction of the device can be easily completed. While the device has some limitations, its robust design allows for simple upkeep and a customizable training experience.
Conclusion: A simplified anatomical design allows for the ReducTrain model to serve as a viable training device for shoulder reductions.
(© 2023. The Author(s).)

Humans, Communication, Software, and Language

Amidst the domestic labor shortage and worldwide pandemic in recent years, there has been an urgent need for a digital means that allows construction site workers, particularly site managers, to obtain information more efficiently in support of their daily managerial tasks. For workers who move around the site, traditional software applications that rely on a form-based interface and require multiple finger movements such as key hits and clicks can be inconvenient and reduce their willingness to use such applications. Conversational AI, also known as a chatbot, can improve the ease of use and usability of a system by providing an intuitive interface for user input. This study presents a demonstrative Natural Language Understanding (NLU) model and prototypes an AI-based chatbot for site managers to inquire about building component dimensions during their daily routines. Building Information Modeling (BIM) techniques are also applied to implement the answering module of the chatbot. The preliminary testing results show that the chatbot can successfully predict the intents and entities behind the inquiries raised by site managers with satisfactory accuracy for both intent prediction and the answer. These results provide site managers with alternative means to retrieve the information they need.

Intelligent sensor systems are essential for building modern Internet of Things applications. Embedding intelligence within or near sensors provides a strong case for analog neural computing. However, rapid prototyping of analog or mixed signal spiking neural computing is a non-trivial and time-consuming task. We introduce mixed-mode neural computing arrays for near-sensor-intelligent computing implemented with Field-Programmable Analog Arrays (FPAA) and Field-Programmable Gate Arrays (FPGA). The combinations of FPAA and FPGA pipelines ensure rapid prototyping and design optimization before finalizing the on-chip implementations. The proposed approach architecture ensures a scalable neural network testing framework along with sensor integration. The experimental set up of the proposed tactile sensing system in demonstrated. The initial simulations are carried out in SPICE, and the real-time implementation is validated on FPAA and FPGA hardware.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2023 Mallan, Gopi, Reghuvaran, Radhakrishnan and James.)

We demonstrate a method to emulate the optical performance of silicon photonic devices fabricated using advanced deep-ultraviolet lithography (DUV) processes on a rapid-prototyping electron-beam lithography process. The method is enabled by a computational lithography predictive model generated by processing SEM image data of the DUV lithography process. We experimentally demonstrate the emulation method's accuracy on integrated silicon Bragg grating waveguides and grating-based, add-drop filter devices, two devices that are particularly susceptible to DUV lithography effects. The emulation method allows silicon photonic device and system designers to experimentally observe the effects of DUV lithography on device performance in a low-cost, rapid-prototyping, electron-beam lithography process to enable a first-time-right design flow.

Dimethylpolysiloxanes, Microfluidics methods, and Microfluidic Analytical Techniques

Soft lithography has permitted rapid prototyping of precise microfluidic features by patterning a deformable elastomer such as polydimethylsiloxane (PDMS) with a photolithographically patterned mold. In microfluidics applications where the flexibility of PDMS is a drawback, a variety of more rigid materials have been proposed. Compared to alternatives, devices fabricated from epoxy and glass have superior mechanical performance, feature resolution, and solvent compatibility. Here we provide a detailed step-by-step method for fabricating rigid microfluidic devices from soft lithography patterned epoxy and glass. The bonding protocol was optimized yielding devices that withstand pressures exceeding 500 psi. Using this method, we demonstrate the use of rigid high aspect ratio spiral microchannels for high throughput cell focusing.
(© 2023. The Author(s).)

Humans, Pregnancy, Female, Pilot Projects, Feasibility Studies, Pregnancy Outcome, Life Change Events, and Prenatal Care

Background: A healthy lifestyle plays a key role in the prevention of lifestyle-related diseases, including subfertility and pregnancy complications. Although the benefits of a healthy lifestyle are well-known, long-term adherence is limited. Moreover, memory for lifestyle-related information as well as medical information provided by the medical professional is often poor and insufficient. In order to innovate and improve health care for both the patients and health care professionals, we developed a prototype of a digital life course care platform (Smarter Health app), providing personalized lifestyle care trajectories integrated in medical care journeys.
Objective: This pilot study aimed to evaluate the feasibility, defined as the actual app use, and the acceptability, which included patient satisfaction and appreciation, of the Smarter Health app.
Methods: Between March 17, 2021, and September 30, 2021, pregnant women familiar with the Dutch language seeking tertiary preconception and pregnancy care were offered the app as part of standard medical care at the outpatient clinic Healthy Pregnancy of the Department of Obstetrics and Gynecology of the Erasmus University Medical Center. Three months after activation of the app, patients received a digital questionnaire consisting of aspects of feasibility and acceptability.
Results: During this pilot study, 440 patients visited the outpatient clinic Healthy Pregnancy. Of the 440 patients, 293 (66.6%) activated the app. Of the 293 patients who activated the app, 125 (42.7%) filled out the questionnaire. Of these 125 patients, 48 (38.4%) used the app. Most app users used it occasionally and logged in 8 times during their medical care trajectory. Overall, app users were satisfied with the app (median 5-point Likert scale=2.4, IQR 2.0-3.3).
Conclusions: Our findings showed that the Smarter Health app, which integrates lifestyle care in medical care, is a feasible health care innovation, and that patients were satisfied with the app. Follow-up and evaluation of pregnancy outcomes should be performed to further substantiate wider clinical implementation.
(©Melissa van der Windt, Sofie Karolina Maria van Zundert, Sam Schoenmakers, Lenie van Rossem, Régine Patricia Maria Steegers-Theunissen. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 20.01.2023.)

Background: Diabetes is a global public health issue, causing burden on healthcare system and increasing risk of mortality. Mobile applications (apps) can be a promising approach to facilitate diabetes self-management. An increasingly utilized approach to facilitate engagement with mobile health (mHealth) technology is to involve potential users in the creation of the technology.
Objective: The aim of this study was to use co-design for type 2 diabetes mellitus (T2DM) self-management mHealth development.
Methods: Three rounds of iterative rapid prototyping panel sessions were conducted with a total of 9 T2DM participants in an Asian setting between Oct 2020 and April 2021. The participants were recruited through convenience sampling. For each round, feedback was gathered through qualitative interviews, and the feedback was used as a reference by the development team to develop and test a more refined version of the app in the next round. Transcribed semi-structured interview data was analyzed thematically using an inductive approach.
Results: Participants' ages ranged from 40 to 69 years. Data saturation was reached, with no new themes emerging from the data. During the sessions, the participants expressed a variety of concerns and feedback on T2DM self-management using EMPOWER app and raised suggestions on the features of ideal T2DM self-management app. Important features include 1) reminders and notifications for medications, 2) Bluetooth integration with glucometers and blood pressure machines to minimize manual entry, 3) enlarged local food database including information on sugar content and recommendations for healthier options, 4) one touch for logging of routine medications and favorite foods, 5) export function for data sharing with physicians. Overall inputs concerned aspects such as user-friendliness of the app, customization possibilities, and educational content for the features in the mobile app.
Conclusion: In this study, we explored users' opinions on a T2DM self-management mobile app using co-design approach. This study adds to the growing body of literature on co-designing behavioral mHealth interventions and can potentially guide researchers in mobile app design for other chronic conditions.
Competing Interests: The authors declare that they have no other competing interests.
(© 2023 Kwan et al.)

Microfluidics methods, Cell Encapsulation, Polymerase Chain Reaction, Microfluidic Analytical Techniques methods, and Microgels

Droplet microfluidics offers a platform from which new digital molecular assay, disease screening, wound healing and material synthesis technologies have been proposed. However, the current commercial droplet generation, assembly and imaging technologies are too expensive and rigid to permit rapid and broad-range tuning of droplet features/cargoes. This rapid prototyping bottleneck has limited further expansion of its application. Herein, an inexpensive home-made pipette droplet microfluidics kit is introduced. This kit includes elliptical pipette tips that can be fabricated with a simple DIY (Do-It-Yourself) tool, a unique tape-based or 3D printed shallow-center imaging chip that allows rapid monolayer droplet assembly/immobilization and imaging with a smart-phone camera or miniature microscope. The droplets are generated by manual or automatic pipetting without expensive and lab-bound microfluidic pumps. The droplet size and fluid viscosity/surface tension can be varied significantly because of our particular droplet generation, assembly and imaging designs. The versatility of this rapid prototyping kit is demonstrated with three representative applications that can benefit from a droplet microfluidic platform: (1) Droplets as microreactors for PCR reaction with reverse transcription to detect and quantify target RNAs. (2) Droplets as microcompartments for spirulina culturing and the optical color/turbidity changes in droplets with spirulina confirm successful photosynthetic culturing. (3) Droplets as templates/molds for controlled synthesis of gold-capped polyacrylamide/gold composite Janus microgels. The easily fabricated and user-friendly portable kit is hence ideally suited for design, training and educational labs.
(© 2023. The Author(s).)

Direct-write printing has contributed tremendously to additive manufacturing; in particular extrusion based printing where it has extended the range of materials for 3D printing and thus enabled use across many more sectors. The printing inks for direct-write printing however, need careful synthesis and invariably undergo extensive preparation before being able to print. Hence, new ink synthesis efforts are required every time a new material is to be printed; this is particularly challenging for low storage modulus (G') materials like silicones, especially at higher resolutions (under 10 µm). Here we report the development of a precise (< 10 µm) 3D printable polymer, with which we 3D print micromoulds which are filled with standard silicones like polydimethylsiloxane (PDMS) and left to cure at room temperature. The proof of concept is demonstrated using a simple water soluble polymer as the mould material. The approach enables micrometre scale silicone structures to be prototyped with ease, away from the cleanroom.
Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Manish K. Tiwari reports financial support was provided by Wellcome EPSRC Centre for Interventional and Surgical Sciences. Manish K. Tiwari reports financial support was provided by European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 714712. Saja Aabith reports financial support was provided by EPSRC DTP studentship award.
(© 2022 The Authors.)

Equipment Design, Transducers, Printing, Three-Dimensional, Ultrasonography, Ultrasonics, and Ultrasonic Therapy

We present a rapid prototyping method for sub-megahertz single-element piezoelectric transducers by using 3D-printed components. In most of the early research phases of applying new sonication ideas, the prototyping quickness is prioritized over the final packaging quality, since the quickness of preliminary demonstration is crucial for promptly determining specific aims and feasible research approaches. We aim to develop a rapid prototyping method for functional ultrasonic transducers to overcome the current long lead time (>a few weeks). Here, we used 3D-printed external housing parts considering a single matching layer and either air backing or epoxy-composite backing (acoustic impedance > 5 MRayl). By molding a single matching layer on the top surface of a piezoceramic in a 3D-printed housing, an entire packaging time was significantly reduced (<26 h) compared to the conventional methods with grinding, stacking, and bonding. We demonstrated this prototyping method for 590-kHz single-element, rectangular-aperture transducers for moderate pressure amplitudes (mechanical index > 1) at focus with temporal pulse controllability (maximum amplitude by <5-cycle burst). We adopted an air-backing design (Type A) for efficient pressure outputs, and bandwidth improvement was tested by a tungsten-composite-backing (Type B) design. The acoustic characterization results showed that the type A prototype provided 3.3 kPa/Vpp far-field transmitting sensitivity with 25.3% fractional bandwidth whereas the type B transducer showed 2.1 kPa/Vpp transmitting sensitivity with 43.3% fractional bandwidth. As this method provided discernable quickness and cost efficiency, this detailed rapid prototyping guideline can be useful for early-phase sonication projects, such as multi-element therapeutic ultrasound array and micro/nanomedicine testing benchtop device prototyping.

Synechococcus genetics

Cyanobacteria are of particular interest for chemical production as they can assimilate CO 2 and use solar energy to power chemical synthesis. However, unlike the model microorganism of Escherichia coli, the availability of genetic toolboxes for rapid proof-of-concept studies in cyanobacteria is generally lacking. In this study, we first characterized a set of promoters to efficiently drive gene expressions in the marine cyanobacterium Synechococcus sp. PCC7002. We identified that the endogenous cpcBA promoter represented one of the strongest promoters in PCC7002. Next, a set of shuttle vectors was constructed based on the endogenous pAQ1 plasmid to facilitate the rapid pathway assembly. Moreover, we used the shuttle vectors to modularly optimize the amorpha-4,11-diene synthesis in PCC7002. By modularly optimizing the metabolic pathway, we managed to redistribute the central metabolism toward the amorpha-4,11-diene production in PCC7002 with enhanced product titer. Taken together, the plasmid toolbox developed in this study will greatly accelerate the generation of genetically engineered PCC7002. KEY POINTS: • Promoter characterization revealed that the endogenous cpcBA promoter represented one of the strongest promoters in PCC7002 • A set of shuttle vectors with different antibiotic selection markers was constructed based on endogenous pAQ1 plasmid • By modularly optimizing the metabolic pathway, amorpha-4,11-diene production in PCC7002 was improved.
(© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Acoustics and Lasers

Acoustic patterning of micro-particles has many important biomedical applications. However, fabrication of such microdevices is costly and labor-intensive. Among conventional fabrication methods, photo-lithography provides high resolution but is expensive and time consuming, and not ideal for rapid prototyping and testing for academic applications. In this work, we demonstrate a highly efficient method for rapid prototyping of acoustic patterning devices using laser manufacturing. With this method we can fabricate a newly designed functional acoustic device in 4 hours. The acoustic devices fabricated using this method can achieve sub-wavelength, complex and non-periodic patterning of microparticles and biological objects with a spatial resolution of 60 μm across a large active manipulation area of 10 × 10 mm 2 .

Humans, Uridine, Pyrimidine Nucleotides, and Uridine Kinase antagonists inhibitors

Pyrimidine nucleotide biosynthesis in humans is a promising chemotherapeutic target for infectious diseases caused by RNA viruses. Because mammalian cells derive pyrimidine ribonucleotides through a combination of de novo biosynthesis and salvage, combined inhibition of dihydroorotate dehydrogenase (DHODH; the first committed step in de novo pyrimidine nucleotide biosynthesis) and uridine/cytidine kinase 2 (UCK2; the first step in salvage of exogenous nucleosides) strongly attenuates viral replication in infected cells. However, while several pharmacologically promising inhibitors of human DHODH are known, to date there are no reports of medicinally viable leads against UCK2. Here, we use structure-based drug prototyping to identify two classes of promising leads that noncompetitively inhibit UCK2 activity. In the process, we have identified a hitherto unknown allosteric site at the intersubunit interface of this homotetrameric enzyme. By reducing the k cat of human UCK2 without altering its K M , these new inhibitors have the potential to enable systematic dialing of the fractional inhibition of pyrimidine salvage to achieve the desired antiviral effect with minimal host toxicity.

Humans, Antihypertensive Agents therapeutic use, Aldosterone therapeutic use, Ghana epidemiology, Renin therapeutic use, Multicenter Studies as Topic, Hypertension, Stroke prevention control, and Stroke drug therapy

Purpose of Review: Worldwide, compared to other racial/ethnic groups, individuals of African ancestry have an excessively higher burden of hypertension-related morbidities, especially stroke. Identifying modifiable biological targets that contribute to these disparities could improve global stroke outcomes. In this scoping review, we discuss how pathological perturbations in the renin-angiotensin-aldosterone pathways could be harnessed via physiological profiling for the purposes of improving blood pressure control for stroke prevention among people of African ancestry.
Recent Findings: Transcontinental comparative data from the USA and Ghana show that the prevalence of treatment-resistant hypertension among stroke survivors is 42.7% among indigenous Africans, 16.1% among African Americans, and 6.9% among non-Hispanic Whites, p < 0.0001. A multicenter clinical trial of patients without stroke in 3 African countries (Nigeria, Kenya, and South Africa) demonstrated that physiological profiling using plasma renin activity and aldosterone to individualize selection of antihypertensive medications compared with usual care resulted in better blood pressure control with fewer medications over 12 months. Among Ghanaian ischemic stroke survivors treated without renin-aldosterone profiling data, an analysis revealed that those with low renin phenotypes did not achieve any meaningful reduction in blood pressure over 12 months on 3-4 antihypertensive medications despite excellent adherence. For a polygenic condition such as hypertension, individualized therapy based on plasma renin-aldosterone-guided selection of therapy for uncontrolled BP following precision medicine principles may be a viable strategy for primary and secondary stroke prevention with the potential to reduce disparities in the poor outcomes of stroke disproportionately shared by individuals of African ancestry. A dedicated clinical trial to test this hypothesis is warranted.
(© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

A low-cost open-source autonomous unmanned surface vehicle (USV) named "iDroneboat" is developed for real-time monitoring and visualization of water quality. The iDroneboat equipped with Internet of Things (IoT) sensors transmits real-time water quality data, including dissolved oxygen (DO), electronical conductivity (EC), pH, and water temperature (WT) to the cloud for data sharing through Long-term Evolution (LTE) communication protocols. Since material and supplies needed are readily accessible from online marketplaces or local hardware stores, the iDroneboat is easily replicable for local water quality studies and citizen-science activities. The iDroneboat appears to be a promising tool to advance environmental research activities, especially for impaired waterways ( e.g. , lakes, rivers, and reservoirs). The preliminary result shows that the proposed low-cost platform, iDroneboat, effectively displays water quality components in real-time to the cloud web services ( e.g. , ThingSpeak), ultimately contributing to citizen science activities and environmental stewardship in water research ecosystems.
Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(© 2022 The Author.)

Gold and Water chemistry

Frozen density embedding (FDE) represents an embedding scheme in which environmental effects are included from first-principles calculations by considering the surrounding system explicitly by means of its electron density. In the present paper, we extend the full four-component relativistic Dirac-Kohn-Sham (DKS) method, as implemented in the BERTHA code, to include environmental and confinement effects with the FDE scheme (DKS-in-DFT FDE). The implementation, based on the auxiliary density fitting techniques, has been enormously facilitated by BERTHA's python API (PyBERTHA), which facilitates the interoperability with other FDE implementations available through the PyADF framework. The accuracy and numerical stability of this new implementation, also using different auxiliary fitting basis sets, has been demonstrated on the simple NH 3 -H 2 O system, in comparison with a reference nonrelativistic implementation. The computational performance has been evaluated on a series of gold clusters (Au n , with n = 2, 4, 8) embedded into an increasing number of water molecules (5, 10, 20, 40, and 80 water molecules). We found that the procedure scales approximately linearly both with the size of the frozen surrounding environment (consistent with the underpinnings of the FDE approach) and with the size of the active system (in line with the use of density fitting). Finally, we applied the code to a series of heavy (Rn) and super-heavy elements (Cn, Fl, Og) embedded in a C 60 cage to explore the confinement effect induced by C 60 on their electronic structure. We compare the results from our simulations, with respect to more-approximate models employed in the atomic physics literature. Our results indicate that the specific interactions described by FDE are able to improve upon the cruder approximations currently employed, and, thus, they provide a basis from which to generate more-realistic radial potentials for confined atoms.

Equipment Design, Motion, and Robotics methods

Designs of soft actuators are mostly guided and limited to certain target functionalities. This article presents a novel programmable design for soft pneumatic bellows-shaped actuators with distinct motions, thus a wide range of functionalities can be engendered through tuning channel parameters. According to the design principle, a kinematic model is established for motion prediction, and a sampling-based optimal parameter search is executed for automatic design. The proposed design method and kinematic models provide a tool for the generation of an optimal channel curve, with respect to target functions and required motion trajectories. Quantitative characterizations on the analytical model are conducted. To validate the functionalities, we generate three types of actuators to cover a wide range of motions in manipulation and locomotion tasks. Comparisons of model prediction on motion trajectory and prototype performance indicate the efficacy of the forward kinematics, and two task-based optimal designs for manipulation scenarios validate the effectiveness of the design parameter search. Prototyped by additive manufacturing technique with soft matter, multifunctional robots in case studies have been demonstrated, suggesting adaptability of the structure and convenience of the soft actuator's automatic design in both manipulation and locomotion. Results show that the novel design method together with the kinematic model paves a way for designing function-oriented actuators in an automatic flow.

This review focuses on fast prototyping advancements in the field of maxillofacial prosthodontics, as well as the various methods for fabricating maxillofacial prostheses. As of date, the interface and software used for processing and designing maxillofacial prostheses are costlier, atypical for the specific purpose, and only reachable to highly trained dental specialists or computer-aided design (CAD) engineers. This review is a summary of all rapid prototyping trials conducted in the mentioned context of three-dimensional (3D) printing of maxillofacial prostheses, treatment modalities, and future perspectives relating to rapid prototyping in dentistry. We performed a search of relevant articles on Google Scholar and PubMed, which yielded a total of 21 articles for full-text reviews. After excluding some articles based on the exclusion criteria, a review was conducted. This study gives a comprehensive discussion of current issues and future ideas for integrating digital technology with conventional techniques.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright © 2022, Bansod et al.)

Databases, Factual, Humans, Software, Knowledge Bases, and Precision Medicine

Background: With significant advancements in the area of precision medicine, the breadth and complexity of the relevant knowledge in the field has increased significantly. However, the difficulty associated with dynamic modelling and the disorganization of such knowledge hinders its rapid development potential.
Results: To overcome the difficulty in using the relational database model for dynamic modelling, and to aid in the organization of precision medicine knowledge, we developed the Mind Mapping Knowledgebase Prototyping (MMKP) tool. The MMKP implements a novel design that we call a "polymorphic foreign key", which allows the establishment of a logical linkage between a single table field and a record from any table. This design has advantages in supporting dynamic changes to the structural relationships in precision medicine knowledge. Knowledge stored in MMKP is presented as a mind map to facilitate human interaction. When using this tool, medical experts may curate the structure and content of the precision knowledge in a flow that is similar to the human thinking process.
Conclusions: The design of polymorphic foreign keys natively supports knowledge modelling in the form of mind mapping, which avoids the hard-coding of medical logic into a rigid database schema and significantly reduces the workload that is required for adapting a relational data model to future changes to the medical logic. The MMKP tool provides a graphical user interface for both data management and knowledgebase prototyping. It supports the flexible customization of the data field constraints and annotations. MMKP is available as open-source code on GitHub: https://github.com/ZjuLiangsl/mmkp.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2022 Liang, Li, Dong and Chen.)

Drug Evaluation, Preclinical methods, Humans, Microfluidics, Precision Medicine, Antineoplastic Agents pharmacology, and Organoids

In vitro tissue models hold great promise for modeling diseases and drug responses. Here, we used emulsion microfluidics to form micro-organospheres (MOSs), which are droplet-encapsulated miniature three-dimensional (3D) tissue models that can be established rapidly from patient tissues or cells. MOSs retain key biological features and responses to chemo-, targeted, and radiation therapies compared with organoids. The small size and large surface-to-volume ratio of MOSs enable various applications including quantitative assessment of nutrient dependence, pathogen-host interaction for anti-viral drug screening, and a rapid potency assay for chimeric antigen receptor (CAR)-T therapy. An automated MOS imaging pipeline combined with machine learning overcomes plating variation, distinguishes tumorspheres from stroma, differentiates cytostatic versus cytotoxic drug effects, and captures resistant clones and heterogeneity in drug response. This pipeline is capable of robust assessments of drug response at individual-tumorsphere resolution and provides a rapid and high-throughput therapeutic profiling platform for precision medicine.
Competing Interests: Conflicts of interest X.S., D.H., and H.C. are co-founders of Xilis, Inc. X.S. left Duke and joined Terasaki Institute and Xilis on November 9, 2021. H.C. is also a member of the board of directors of Roche. H.C.’s full disclosure is given at https://www.uu.nl/staff/JCClevers/. Z.W. recently left Duke University and joined Xilis, Inc. as a full-time employee. Patents WO2020242594, US 2021/0285054, and US 2022/006279 are related to this work.
(Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Electrodes, Ion-Selective Electrodes, Ions, Potassium, Potentiometry, Printing, Three-Dimensional, Sodium, Internet of Things, and Robotics

We report automated fabrication of solid-contact sodium-selective (Na + -ISEs) and potassium-selective electrodes (K + -ISEs) using a 3D printed liquid handling robot controlled with Internet of Things (IoT) technology. The printing system is affordable and can be customized for the use with micropipettes for applications such as drop-casting, biological assays, sample preparation, rinsing, cell culture, and online analyte monitoring using multi-well plates. The robot is more compact (25 × 30 × 35 cm) and user-friendly than commercially available systems and does not require mechatronic experience. For fabrication of ion-selective electrodes, a carbon black intermediate layer and ion-selective membrane were successively drop-cast on the surface of stencil-printed carbon electrode using the dispensing robot. The 3D-printed robot increased ISE robustness while decreasing the modification time by eliminating manual steps. The Na + -ISEs and K + -ISEs were characterized for their potentiometric responses using a custom-made, low-cost (<$25) multi-channel smartphone-based potentiometer capable of signal processing and wireless data transmission. The electrodes showed Nernstian responses of 58.2 ± 2.6 mV decade -1 and 56.1 ± 0.7 mV decade -1 for Na + and K + , respectively with an LOD of 1.0 × 10 -5  M. We successfully applied the ISEs for multiplexed detection of Na + and K + in urine and artificial sweat samples at clinically relevant concentration ranges. The 3D-printed pipetting robot cost $100 and will pave the way for more accessible mass production of ISEs for those who cannot afford the expensive commercial robots.
(Copyright © 2022 Elsevier B.V. All rights reserved.)

Biocatalysis, Capsid Proteins genetics, Capsid Proteins metabolism, Catalysis, Nanotechnology, and Bacteriophage P22 metabolism

Protein cages are attractive as molecular scaffolds for the fundamental study of enzymes and metabolons and for the creation of biocatalytic nanoreactors for in vitro and in vivo use. Virus-like particles (VLPs) such as those derived from the P22 bacteriophage capsid protein make versatile self-assembling protein cages and can be used to encapsulate a broad range of protein cargos. In vivo encapsulation of enzymes within VLPs requires fusion to the coat protein or a scaffold protein. However, the expression level, stability, and activity of cargo proteins can vary upon fusion. Moreover, it has been shown that molecular crowding of enzymes inside VLPs can affect their catalytic properties. Consequently, testing of numerous parameters is required for production of the most efficient nanoreactor for a given cargo enzyme. Here, we present a set of acceptor vectors that provide a quick and efficient way to build, test, and optimize cargo loading inside P22 VLPs. We prototyped the system using a yellow fluorescent protein and then applied it to mevalonate kinases (MKs), a key enzyme class in the industrially important terpene (isoprenoid) synthesis pathway. Different MKs required considerably different approaches to deliver maximal encapsulation as well as optimal kinetic parameters, demonstrating the value of being able to rapidly access a variety of encapsulation strategies. The vector system described here provides an approach to optimize cargo enzyme behavior in bespoke P22 nanoreactors. This will facilitate industrial applications as well as basic research on nanoreactor-cargo behavior.

In synthetic biology, biosensors are routinely coupled with a gene expression system for detecting small molecules and physical signals. We reveal a fluorescent complex, based on the interaction of an Escherichia coli double bond reductase ( Ec CurA), as a detection unit with its substrate curcumin-we call this a direct protein (DiPro) biosensor. Using a cell-free synthetic biology approach, we use the Ec CurA DiPro biosensor to fine tune 10 reaction parameters (cofactor, substrate, and enzyme levels) for cell-free curcumin biosynthesis, assisted through acoustic liquid handling robotics. Overall, we increase Ec CurA-curcumin DiPro fluorescence within cell-free reactions by 78-fold. This finding adds to the growing family of protein-ligand complexes that are naturally fluorescent and potentially exploitable for a range of applications, including medical imaging to engineering high-value chemicals.
Competing Interests: The authors declare no conflict of interest.
(© 2022 The Authors. Engineering Biology published by John Wiley & Sons Ltd on behalf of The Institution of Engineering and Technology.)

Lab-On-A-Chip Devices, Microtechnology, Printing, Three-Dimensional, Microfluidics methods, and Stereolithography

Stereolithography based 3D printing of microfluidics for prototyping has gained a lot of attention due to several advantages such as fast production, cost-effectiveness, and versatility over traditional photolithography-based microfabrication techniques. However, existing consumer focused SLA 3D printers struggle to fabricate functional microfluidic devices due to several challenges associated with micron-scale 3D printing. Here, we explore the origins and mechanism of the associated failure modes followed by presenting guidelines to overcome these challenges. The prescribed method works completely with existing consumer class inexpensive SLA printers without any modifications to reliably print PDMS cast microfluidic channels with channel sizes as low as ~75 μm and embedded channels with channel sizes as low ~200 μm. We developed a custom multi-resin formulation by incorporating Polyethylene glycol diacrylate (PEGDA) and Ethylene glycol polyether acrylate (EGPEA) as the monomer units to achieve micron sized printed features with tunable mechanical and optical properties. By incorporating multiple resins with different mechanical properties, we were able to achieve spatial control over the stiffness of the cured resin enabling us to incorporate both flexible and rigid components within a single 3D printed microfluidic chip. We demonstrate the utility of this technique by 3D printing an integrated pressure-actuated pneumatic valve (with flexible cured resin) in an otherwise rigid and clear microfluidic device that can be fabricated in a one-step process from a single CAD file. We also demonstrate the utility of this technique by integrating a fully functional finger-actuated microfluidic pump. The versatility and accessibility of the demonstrated fabrication method have the potential to reduce our reliance on expensive and time-consuming photolithographic techniques for microfluidic chip fabrication and thus drastically lowering our barrier to entry in microfluidics research.
Competing Interests: The authors declare no conflict of interest

Hospitals, Humans, Retrospective Studies, Workflow, Artificial Intelligence, and Radiology methods

The field of artificial intelligence (AI) in medical imaging is undergoing explosive growth, and Radiology is a prime target for innovation. The American College of Radiology Data Science Institute has identified more than 240 specific use cases where AI could be used to improve clinical practice. In this context, thousands of potential methods are developed by research labs and industry innovators. Deploying AI tools within a clinical enterprise, even on limited retrospective evaluation, is complicated by security and privacy concerns. Thus, innovation must be weighed against the substantive resources required for local clinical evaluation. To reduce barriers to AI validation while maintaining rigorous security and privacy standards, we developed the AI Imaging Incubator. The AI Imaging Incubator serves as a DICOM storage destination within a clinical enterprise where images can be directed for novel research evaluation under Institutional Review Board approval. AI Imaging Incubator is controlled by a secure HIPAA-compliant front end and provides access to a menu of AI procedures captured within network-isolated containers. Results are served via a secure website that supports research and clinical data formats. Deployment of new AI approaches within this system is streamlined through a standardized application programming interface. This manuscript presents case studies of the AI Imaging Incubator applied to randomizing lung biopsies on chest CT, liver fat assessment on abdomen CT, and brain volumetry on head MRI.
(© 2022. The Author(s) under exclusive licence to Society for Imaging Informatics in Medicine.)

We demonstrate a real-time coherent optical receiver based on a single field programmable gate array (FPGA) chip. To strike the balance between the performance and hardware resources, we use a clock recovery scheme using the optimal interpolation (OI). The performance and complexity of the OI-based scheme and the traditional schemes are compared and discussed via offline digital signal processing. And a real-time 15GBaud single-polarization 16QAM transmission experiment under different received optical power using the FPGA-based receiver is carried out to demonstrate the overall performance of different clock recovery and equalization schemes. The result proves that, compared to the traditional scheme with a cubic interpolator and a 7-tap equalizer, the optimal interpolator significantly lowers the utilization of LUT, CARRY8, and DSP48 by 35%, 50%, and 11%, respectively, and can work properly under a received optical power of -40dBm.

Humans, Hydrogels, Microvessels, Neovascularization, Pathologic, Lab-On-A-Chip Devices, and Microtechnology

Reconstruction of 3D vascularized microtissues within microfabricated devices has rapidly developed in biomedical engineering, which can better mimic the tissue microphysiological function and accurately model human diseases in vitro . However, the traditional PDMS-based microfluidic devices suffer from the microfabrication with complex processes and usage limitations of either material properties or microstructure design, which drive the demand for easy processing and more accessible devices with a user-friendly interface. Here, we present an open microfluidic device through a rapid prototyping method by laser cutting in a cost-effective manner with high flexibility and compatibility. This device allows highly efficient and robust hydrogel patterning under a liquid guiding rail by spontaneous capillary action without the need for surface treatment. Different vascularization mechanisms including vasculogenesis and angiogenesis were performed to construct a 3D perfusable microvasculature inside a tissue chamber with various shapes under different microenvironment factors. Furthermore, as a proof-of-concept we have created a vascularized spheroid by placing a monoculture spheroid into the central through-hole of this device, which formed angiogenesis between the spheroid and microvascular network. This open microfluidic device has great potential for mass customization without the need for complex microfabrication equipment in the cleanroom, which can facilitate studies requiring high-throughput and high-content screening.

Electrodes and Ions chemistry

Traveling wave structures for lossless ion manipulation (TW-SLIM) has proven a valuable tool for the separation and study of gas-phase ions. Unfortunately, many of the traditional components of TW-SLIM experiments manifest practical and financial barriers to the technique's broad implementation. To this end, a series of technological innovations and methodologies are presented which enable for simplified SLIM experimentation and more rapid TW-SLIM prototyping. In addition to the use of multiple independent board sets that comprise the present SLIM system, we introduce a low-cost, multifunctional traveling wave generator to produce TW within the TW-SLIM. This square-wave producing unit proved effective in realizing TW-SLIM separations compared to traditional approaches. Maintaining a focus on lowering barriers to implementation, the present set of experiments explores the use of on-board injection (OBI) methods, which offer potential alternatives to ion funnel traps. These OBI techniques proved feasible and the ability of this simplified TW-SLIM platform to enhance ion accumulation was established. Further experimentation regarding ion accumulation revealed a complexity to ion accumulation within TW-SLIM that has yet to be expounded upon. Lastly, the ability of the presented TW-SLIM platform to store ions for extended periods (1 s) without significant loss (<10%) was demonstrated. The aforementioned experiments clearly establish the efficacy of a simplified TW-SLIM platform which promises to expand adoption and experimentation of the technique.
(Copyright © 2022 Elsevier B.V. All rights reserved.)

Gene Library, Protein Biosynthesis, Synthetic Biology, High-Throughput Screening Assays, and Microfluidics methods

Engineering regulatory parts for improved performance in genetic programs has played a pivotal role in the development of the synthetic biology cell programming toolbox. Here, we report the development of a novel high-throughput platform for regulatory part prototyping and analysis that leverages the advantages of engineered DNA libraries, cell-free protein synthesis (CFPS), high-throughput emulsion droplet microfluidics, standard flow sorting adapted to screen droplet reactions, and next-generation sequencing (NGS). With this integrated platform, we screened the activity of millions of genetic parts within hours, followed by NGS retrieval of the improved designs. This in vitro platform is particularly valuable for engineering regulatory parts of nonmodel organisms, where in vivo high-throughput screening methods are not readily available. The platform can be extended to multipart screening of complete genetic programs to optimize yield and stability.

Autotrophic Processes, Fermentation, Oxidation-Reduction, Carbon Cycle, and Escherichia coli metabolism

Carbon-negative synthesis of biochemical products has the potential to mitigate global CO 2 emissions. An attractive route to do this is the reverse β-oxidation (r-BOX) pathway coupled to the Wood-Ljungdahl pathway. Here, we optimize and implement r-BOX for the synthesis of C4-C6 acids and alcohols. With a high-throughput in vitro prototyping workflow, we screen 762 unique pathway combinations using cell-free extracts tailored for r-BOX to identify enzyme sets for enhanced product selectivity. Implementation of these pathways into Escherichia coli generates designer strains for the selective production of butanoic acid (4.9 ± 0.1 gL -1 ), as well as hexanoic acid (3.06 ± 0.03 gL -1 ) and 1-hexanol (1.0 ± 0.1 gL -1 ) at the best performance reported to date in this bacterium. We also generate Clostridium autoethanogenum strains able to produce 1-hexanol from syngas, achieving a titer of 0.26 gL -1 in a 1.5 L continuous fermentation. Our strategy enables optimization of r-BOX derived products for biomanufacturing and industrial biotechnology.
(© 2022. The Author(s).)

In preparation for new-generation imaging spectrometer missions and the accompanying unprecedented inflow of hyperspectral data, optimized models are needed to generate vegetation traits routinely. Hybrid models, combining radiative transfer models with machine learning algorithms, are preferred, however, dealing with spectral collinearity imposes an additional challenge. In this study, we analyzed two spectral dimensionality reduction methods: principal component analysis (PCA) and band ranking (BR), embedded in a hybrid workflow for the retrieval of specific leaf area (SLA), leaf area index (LAI), canopy water content (CWC), canopy chlorophyll content (CCC), the fraction of absorbed photosynthetic active radiation (FAPAR), and fractional vegetation cover (FVC). The SCOPE model was used to simulate training data sets, which were optimized with active learning. Gaussian process regression (GPR) algorithms were trained over the simulations to obtain trait-specific models. The inclusion of PCA and BR with 20 features led to the so-called GPR-20PCA and GPR-20BR models. The 20PCA models encompassed over 99.95% cumulative variance of the full spectral data, while the GPR-20BR models were based on the 20 most sensitive bands. Validation against in situ data obtained moderate to optimal results with normalized root mean squared error (NRMSE) from 13.9% (CWC) to 22.3% (CCC) for GPR-20PCA models, and NRMSE from 19.6% (CWC) to 29.1% (SLA) for GPR-20BR models. Overall, the GPR-20PCA slightly outperformed the GPR-20BR models for all six variables. To demonstrate mapping capabilities, both models were tested on a PRecursore IperSpettrale della Missione Applicativa (PRISMA) scene, spectrally resampled to Copernicus Hyperspectral Imaging Mission for the Environment (CHIME), over an agricultural test site (Jolanda di Savoia, Italy). The two strategies obtained plausible spatial patterns, and consistency between the two models was highest for FVC and LAI ( R 2 = 0.91, R 2 = 0.86) and lowest for SLA mapping ( R 2 = 0.53). From these findings, we recommend implementing GPR-20PCA models as the most efficient strategy for the retrieval of multiple crop traits from hyperspectral data streams. Hence, this workflow will support and facilitate the preparations of traits retrieval models from the next-generation operational CHIME.
Competing Interests: Conflicts of Interest: The authors declare no conflict of interest.

Humans, Intelligence, and Software

Sensor networks have dynamically expanded our ability to monitor and study the world. Their presence and need keep increasing, and new hardware configurations expand the range of physical stimuli that can be accurately recorded. Sensors are also no longer simply recording the data, they process it and transform into something useful before uploading to the cloud. However, building sensor networks is costly and very time consuming. It is difficult to build upon other people's work and there are only a few open-source solutions for integrating different devices and sensing modalities. We introduce REIP, a Reconfigurable Environmental Intelligence Platform for fast sensor network prototyping. REIP's first and most central tool, implemented in this work, is an open-source software framework, an SDK, with a flexible modular API for data collection and analysis using multiple sensing modalities. REIP is developed with the aim of being user-friendly, device-agnostic, and easily extensible, allowing for fast prototyping of heterogeneous sensor networks. Furthermore, our software framework is implemented in Python to reduce the entrance barrier for future contributions. We demonstrate the potential and versatility of REIP in real world applications, along with performance studies and benchmark REIP SDK against similar systems.

Despite evidence associating the use of mechanical circulatory support (MCS) devices with increased survival and quality of life in patients with advanced heart failure (HF), significant complications and high costs limit their clinical use. We aimed to design an innovative MCS device to address three important needs: low cost, minimally invasive implantation techniques, and low risk of infection. We used mathematical modeling to calculate the pump characteristics to deliver variable flows at different pump diameters, turbomachinery design software CFturbo (2020 R2.4 CFturbo GmbH, Dresden, Germany) to create the conceptual design of the pump, computational fluid dynamics analysis with Solidworks Flow Simulation to in silico test pump performance, Solidworks (Dassault Systèmes SolidWorks Corporation, Waltham, MA, USA) to further refine the design, 3D printing with polycarbonate filament for the initial prototype, and a stereolithography printer (Form 2, Formlabs, Somerville, MA, USA) for the second variant materialization. We present the concept, design, and early prototyping of a low-cost, minimally invasive, fully implantable in a subcutaneous pocket MCS device for long-term use and partial support in patients with advanced HF which unloads the left heart into the arterial system containing a rim-driven, hubless axial-flow pump and the wireless transmission of energy. We describe a low-cost, fully implantable, low-invasive, wireless power transmission left ventricular assist device that has the potential to address patients with advanced HF with higher impact, especially in developing countries. In vitro testing will provide input for further optimization of the device before proceeding to a completely functional prototype that can be implanted in animals.

Electrodes, Glucose, Gold chemistry, Hydrogen Peroxide, Silver, Electrochemical Techniques, and Microfluidics

We present a low-cost, accessible, and rapid fabrication process for electrochemical microfluidic sensors. This work leverages the accessibility of consumer-grade electronic craft cutters as the primary tool for patterning of sensor electrodes and microfluidic circuits, while commodity materials such as gold leaf, silver ink pen, double-sided tape, plastic transparency films, and fabric adhesives are used as its base structural materials. The device consists of three layers, the silver reference electrode layer at the top, the PET fluidic circuits in the middle and the gold sensing electrodes at the bottom. Separation of the silver reference electrode from the gold sensing electrodes reduces the possibility of cross-contamination during surface modification. A novel approach in mesoscale patterning of gold leaf electrodes can produce generic designs with dimensions as small as 250 μm. Silver electrodes with dimensions as small as 385 μm were drawn using a plotter and a silver ink pen, and fluid microchannels as small as 300 μm were fabricated using a sandwich of iron-on adhesives and PET. Device layers are then fused together using an office laminator. The integrated microfluidic electrochemical platform has electrode kinetics/performance of Δ E p = 91.3 mV, I pa / I pc = 0.905, characterized by cyclic voltammetry using a standard ferrocyanide redox probe, and this was compared against a commercial screen-printed gold electrode (Δ E p = 68.9 mV, I pa / I pc = 0.984). To validate the performance of the integrated microfluidic electrochemical platform, a catalytic hydrogen peroxide sensor and enzyme-coupled glucose biosensors were developed as demonstrators. Hydrogen peroxide quantitation achieves a limit of detection of 0.713 mM and sensitivity of 78.37 μA mM -1 cm -2 , while glucose has a limit of detection of 0.111 mM and sensitivity of 12.68 μA mM -1 cm -2 . This rapid process allows an iterative design-build-test cycle in under 2 hours. The upfront cost to set up the system is less than USD 520, with each device costing less than USD 0.12, making this manufacturing process suitable for low-resource laboratories or classroom settings.

Background: Augmented reality (AR) and brain-computer interface (BCI) are promising technologies that have a tremendous potential to revolutionize health care. While there has been a growing interest in these technologies for medical applications in the recent years, the combined use of AR and BCI remains a fairly unexplored area that offers significant opportunities for improving health care professional education and clinical practice. This paper describes a recent study to explore the integration of AR and BCI technologies for health care applications.
Objective: The described effort aims to advance an understanding of how AR and BCI technologies can effectively work together to transform modern health care practice by providing new mechanisms to improve patient and provider learning, communication, and shared decision-making.
Methods: The study methods included an environmental scan of AR and BCI technologies currently used in health care, a use case analysis for a combined AR-BCI capability, and development of an integrated AR-BCI prototype solution for health care applications.
Results: The study resulted in a novel interface technology solution that enables interoperability between consumer-grade wearable AR and BCI devices and provides the users with an ability to control digital objects in augmented reality using neural commands. The article discusses this novel solution within the context of practical digital health use cases developed during the course of the study where the combined AR and BCI technologies are anticipated to produce the most impact.
Conclusions: As one of the pioneering efforts in the area of AR and BCI integration, the study presents a practical implementation pathway for AR-BCI integration and provides directions for future research and innovation in this area.
(©Anya Andrews. Originally published in JMIR Formative Research (https://formative.jmir.org), 21.04.2022.)

Crown Lengthening, Humans, Printing, Three-Dimensional, Stereolithography, Computer-Aided Design, and Dental Implants

Progress with additive 3D printing is revolutionizing biomaterial manufacturing, including clinical dentistry and prosthodontics. Among the several 3D additive printing technologies, stereolithography is very popular as it utilizes light-activated resin for precise resolution. A simplified digital technique was used to fabricate two designs of a surgical guide for crown lengthening. Two cases are presented that utilized digital imaging and communications in medicine (DICOM) files obtained with computed tomography (CT) imaging and processed using four CAD software (Blue Sky Plan, Exocad, Meshmixer and 3D Slicer). The final models were converted to standard tessellation (STL) files and the guides were 3D printed with an additive stereolithography (SLA) printer. The first case was fabricated with a bone model from cone beam computed tomography (CBCT) data, and the second case was generated with intraoral and wax-up scans alone. Both methods appear to be equally effective compared to using a conventional method of guide frabication. However, proximal bone reduction was a concern with both designs. Digitally fabricated 3D printed surgical guide for crown lengthening has merit and a practical design is needed for future clinical validation.
(© 2021 by the American College of Prosthodontists.)

This paper demonstrates laser forming, localized heating with a laser to induce plastic deformation, can self-fold 2D printed circuit boards (PCBs) into 3D structures with electronic function. There are many methods for self-folding but few are compatible with electronic materials. We use a low-cost commercial laser writer to both cut and fold a commercial flexible PCB. Laser settings are tuned to select between cutting and folding with higher power resulting in cutting and lower power resulting in localized heating for folding into 3D shapes. Since the thin copper traces used in commercial PCBs are highly reflective and difficult to directly fold, two approaches are explored for enabling folding: plating with a nickel/gold coating or using a single, high-power laser exposure to oxidize the surface and improve laser absorption. We characterized the physical effect of the exposure on the sample as well as the fold angle as a function of laser passes and demonstrate the ability to lift weights comparable with circuit packages and passive components. This technique can form complex, multifold structures with integrated electronics; as a demonstrator, we fold a commercial board with a common timing circuit. Laser forming to add a third dimension to printed circuit boards is an important technology to enable the rapid prototyping of complex 3D electronics.

Exoskeletons and more in general wearable mechatronic devices represent a promising opportunity for rehabilitation and assistance to people presenting with temporary and/or permanent diseases. However, there are still some limits in the diffusion of robotic technologies for neuro-rehabilitation, notwithstanding their technological developments and evidence of clinical effectiveness. One of the main bottlenecks that constrain the complexity, weight, and costs of exoskeletons is represented by the actuators. This problem is particularly evident in devices designed for the upper limb, and in particular for the hand, in which dimension limits and kinematics complexity are particularly challenging. This study presents the design and prototyping of a hand finger exoskeleton. In particular, we focus on the design of a gear-based differential mechanism aimed at coupling the motion of two adjacent fingers and limiting the complexity and costs of the system. The exoskeleton is able to actuate the flexion/extension motion of the fingers and apply bidirectional forces, that is, it is able to both open and close the fingers. The kinematic structure of the finger actuation system has the peculiarity to present three DoFs when the exoskeleton is not worn and one DoF when it is worn, allowing better adaptability and higher wearability. The design of the gear-based differential is inspired by the mechanism widely used in the automotive field; it allows actuating two fingers with one actuator only, keeping their movements independent.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2022 Dragusanu, Troisi, Villani, Prattichizzo and Malvezzi.)

Post-traumatic reconstruction of the orbit can pose a challenge due to inherent intraoperative problems. Intra-orbital adipose tissue is difficult to manipulate and retract making visualization of the posterior orbital contents difficult. Rapid prototyping (RP) is a cost-effective method of anatomical model production allowing the surgeon to produce a patient specific implant (PSI) which can be pre-surgically adapted to the orbital defect with exact reconstruction. Intraoperative imaging allows immediate assessment of reconstruction at the time of surgery. Utilization and combination of both technologies improves accuracy of reconstruction with orbital implants and reduces cost, surgical time, and the rate of revision surgery.
Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
(© The Author(s) 2021.)

Adult, Dental Pulp Cavity, Humans, Root Canal Therapy, Tooth Root, Transplantation, Autologous, Treatment Outcome, Surgery, Computer-Assisted, and Tooth

Background: Autotransplantation is a beneficial treatment with a high success rate for young patients. However, most adult patients require root canal treatment (RCT) of the donor teeth after the autotransplantation procedure, which causes a prolonged treatment time and additional expenses and increases the rate of future tooth fracture. Rapid prototyping (RP)-assisted autotransplantation shortens the extra-alveolar time and enables a superior clinical outcome. However, no cohort studies of the application of this method on adult populations have been reported.
Methods: This study is a retrospective cohort study. All patients underwent autotransplantation from 2012 to 2020 in the Kaohsiung and Chia-Yi branches of Chang Gung Memorial Hospital, and the procedure and clinical outcomes were analysed. Differences in clinical outcomes, age, sex, extra-alveolar time, fixation method, and RCT rate were compared between the two groups.
Results: We enrolled 21 patients, 13 treated using the conventional method and 8 treated using the RP-based technique. The RCT rates of the conventional group and RP group were 92.3% and 59%, respectively. The mean age of the two groups was significantly different (28.8 ± 10 vs. 21.6 ± 2.1); after performing subgroup analysis by excluding all of the patients aged > 40 years, we found that the RCT rates were still significantly different (91.0% vs. 50%). The mean extra-alveolar time was 43 s in the RP group, and the autotransplantation survival rate in both groups was 100%.
Conclusions: Rapid prototyping-assisted autotransplantation was successfully adopted for all patients in our study population. By shortening the extra-alveolar time, only 50% of the patients required a root canal treatment with a 100% autotransplantation survival rate.
Trial Registration: Retrospectively registered.
(© 2022. The Author(s).)

Transforming lab research into a sustainable business is becoming a trend in the microfluidic field. However, there are various challenges during the translation process due to the gaps between academia and industry, especially from laboratory prototyping to industrial scale-up production, which is critical for potential commercialization. In this Perspective, based on our experience in collaboration with stakeholders, e.g., biologists, microfluidic engineers, diagnostic specialists, and manufacturers, we aim to share our understanding of the manufacturing process chain of microfluidic cartridge from concept development and laboratory prototyping to scale-up production, where the scale-up production of commercial microfluidic cartridges is highlighted. Four suggestions from the aspect of cartridge design for manufacturing, professional involvement, material selection, and standardization are provided in order to help scientists from the laboratory to bring their innovations into pre-clinical, clinical, and mass production and improve the manufacturability of laboratory prototypes toward commercialization.
(© 2022 Author(s).)

Gait, Humans, Neural Networks, Computer, Recognition, Psychology, Apathy, and Wearable Electronic Devices

Human gait is a unique behavioral characteristic that can be used to recognize individuals. Collecting gait information widely by the means of wearable devices and recognizing people by the data has become a topic of research. While most prior studies collected gait information using inertial measurement units, we gather the data from 40 people using insoles, including pressure sensors, and precisely identify the gait phases from the long time series using the pressure data. In terms of recognizing people, there have been a few recent studies on neural network-based approaches for solving the open set gait recognition problem using wearable devices. Typically, these approaches determine decision boundaries in the latent space with a limited number of samples. Motivated by the fact that such methods are sensitive to the values of hyper-parameters, as our first contribution, we propose a new network model that is less sensitive to changes in the values using a new prototyping encoder-decoder network architecture. As our second contribution, to overcome the inherent limitations due to the lack of transparency and interpretability of neural networks, we propose a new module that enables us to analyze which part of the input is relevant to the overall recognition performance using explainable tools such as sensitivity analysis (SA) and layer-wise relevance propagation (LRP).
Competing Interests: The authors have declared that no competing interests exist.

Capillary Action, Polymers, Porosity, Lab-On-A-Chip Devices, and Microfluidics

Paper-based microfluidics was initially developed for use in ultra-low-cost diagnostics powered passively by liquid wicking. However, there is significant untapped potential in using paper to internally guide porous microfluidic flows using externally applied pressure gradients. Here, we present a new technique for fabricating and utilizing low-cost polymer-laminated paper-based microfluidic devices using external pressure. Known as microfluidic pressure in paper (μPiP), devices fabricated by this technique are capable of sustaining a pressure gradient for use in precise liquid handling and manipulation applications similar to conventional microfluidic open-channel designs, but instead where fluid is driven directly through the porous paper structure. μPiP devices can be both rapidly prototyped or scalably manufactured and deployed at commercial scale with minimal time, equipment, and training requirements. We present an analysis of continuous pressure-driven flow in porous paper-based microfluidic channels and demonstrate broad applicability of this method in performing a variety of different liquid handling applications, including measuring red blood cell deformability and performing continuous free-flow DNA electrophoresis. This new platform offers a budget-friendly method for performing microfluidic operations for both academic prototyping and large-scale commercial device production.

Germplasm repositories can benefit sustainable aquaculture by supporting genetic improvement, assisted reproduction, and management of valuable genetic resources. Lack of reliable quality management tools has impeded repository development in the past several decades. Microfabricated open-hardware devices have emerged as a new approach to assist repository development by providing standardized quality assessment capabilities to enable routine quality control. However, prototyping of microfabricated devices (microdevices) traditionally relies on photolithography techniques that are costly, time intensive, and accessible only through specialized engineering laboratories. Although resin 3-D printing has been introduced into the microfabrication domain, existing publications focus on customized or high-cost (>thousands of USD) printers. The goal of this report was to identify and call attention to the emerging opportunities to support innovation in microfabrication by use of low-cost (prototyping. We demonstrate that low-cost mask-based stereolithography (MSLA) 3-D printers with straightforward modifications can provide fabrication quality that approaches traditional photolithography techniques. For example, reliable feature sizes of 20 μm with dimensional discrepancy of <4% for lateral dimensions and <5% for vertical dimensions were fabricated with a consumer-level MSLA printers. In addition, alterations made to pre-processing, post-processing, and printer configuration steps improved print quality as demonstrated in objects with sharper edges and smoother surfaces. The prototyping time and cost of resin 3-D printing (3 h with USD 0.5/prototype) were considerably lower than those of traditional photolithography (5 d with USD 80/prototype). With the rapid advance of consumer-grade printers, resin 3-D printing can revolutionize rapid prototyping approaches for microdevices in the near future, facilitating participation in interdisciplinary development of innovative hardware to support germplasm repository development for aquatic species.
Competing Interests: Conflicts of Interest: The authors declare no conflict of interest.

Electrochemical Techniques, Electrodes, Microfluidics, Aptamers, Nucleotide, and Biosensing Techniques

We demonstrate the ability to rapidly prototype and fabricate an epoxy-embedded electrode platform and microfluidic device suitable for using electrochemical biosensors under flow conditions. We utilize three-dimensional (3-D) printing to rapidly prototype molds to fabricate epoxy-embedded electrodes in addition to molds for rapid prototyping of PDMS microfluidic components. We characterize the bare gold epoxy-embedded electrodes using ferricyanide as a redox indicator and then characterize the performance of an adenosine triphosphate (ATP) specific electrochemical, aptamer-based (E-AB) sensor. We then incorporate the ATP specific E-AB sensors into the microfluidic device to study and take advantage of the dynamic response this class of sensor offers. We were able to flow varying concentrations of target analyte and monitor the dynamic response of the sensors to the changing concentration. This work demonstrates the ability to rapidly prototype E-AB sensors under flow conditions using 3-D printing which can lead to rapid and affordable point-of-care or fieldable applications where dynamic measurements of concentration, specificity and sensitivity and multiplex detection are necessary.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2021 Elsevier B.V. All rights reserved.)

Culture Media, Plastics, Workflow, Laboratories, and Printing, Three-Dimensional

Although the microbiology laboratory paradigm has increasingly changed from manual to automated procedures, and from functional to molecular methods, traditional culture methods remain vital. Using inexpensive desktop fused filament fabrication 3D printing, we designed, produced and tested rapid prototypes of customised labware for microbial culture namely frames to make dip slides, inoculation loops, multi-pin replicators, and multi-well culture plates for solid medium. These customised components were used to plate out samples onto solid media in various formats, and we illustrate how they can be suitable for many microbiological methods such as minimum inhibitory concentration tests, or for directly detecting pathogens from mastitis samples, illustrating the flexibility of rapid-prototyped culture consumable parts for streamlining microbiological methods. We describe the methodology needed for microbiologists to develop their own novel and unique tools, or to fabricate and customise existing consumables. A workflow is presented for designing and 3D printing labware and quickly producing easy-to-sterilise and re-useable plastic parts of great utility in the microbiology laboratory.
(© 2021 The Society for Applied Microbiology.)

Animals, Antibodies, Cost-Benefit Analysis, Data Interpretation, Statistical, Disulfides, Drosophila melanogaster, Escherichia coli, Female, Gene Expression Regulation drug effects, Humans, Leishmania, Peptides genetics, Protein Aggregates, Protein Domains, RNA, Ribosomal, 16S, Synthetic Biology, Thermodynamics, Cell-Free System drug effects, Drugs, Generic chemistry, Drugs, Generic pharmacology, Peptides chemistry, and Peptides pharmacology

Advances in peptide and protein therapeutics increased the need for rapid and cost-effective polypeptide prototyping. While in vitro translation systems are well suited for fast and multiplexed polypeptide prototyping, they suffer from misfolding, aggregation and disulfide-bond scrambling of the translated products. Here we propose that efficient folding of in vitro produced disulfide-rich peptides and proteins can be achieved if performed in an aggregation-free and thermodynamically controlled folding environment. To this end, we modify an E. coli-based in vitro translation system to allow co-translational capture of translated products by affinity matrix. This process reduces protein aggregation and enables productive oxidative folding and recycling of misfolded states under thermodynamic control. In this study we show that the developed approach is likely to be generally applicable for prototyping of a wide variety of disulfide-constrained peptides, macrocyclic peptides with non-native bonds and antibody fragments in amounts sufficient for interaction analysis and biological activity assessment.
(© 2022. The Author(s).)

Background: Medical students show low levels of e-mental health literacy. Moreover, there is a high prevalence of common mental illnesses among medical students. Mobile health (mHealth) apps can be used to maintain and promote medical students' well-being. To date, the potential of mHealth apps for promoting mental health among medical students is largely untapped because they seem to lack familiarity with mHealth. In addition, little is known about medical students' preferences regarding mHealth apps for mental health promotion. There is a need for guidance on how to promote competence-based learning on mHealth apps in medical education.
Objective: The aim of this case study is to pilot an innovative concept for an educative workshop following a participatory co-design approach and to explore medical students' preferences and ideas for mHealth apps through the design of a hypothetical prototype.
Methods: We conducted a face-to-face co-design workshop within an elective subject with 26 participants enrolled at a medical school in Germany on 5 consecutive days in early March 2020. The aim of the workshop was to apply the knowledge acquired from the lessons on e-mental health and mHealth app development. Activities during the workshop included group work, plenary discussions, storyboarding, developing personas (prototypical users), and designing prototypes of mHealth apps. The workshop was documented in written and digitalized form with the students' permission.
Results: The participants' feedback suggests that the co-design workshop was well-received. The medical students presented a variety of ideas for the design of mHealth apps. Among the common themes that all groups highlighted in their prototypes were personalization, data security, and the importance of scientific evaluation.
Conclusions: Overall, this case study indicates the feasibility and acceptance of a participatory design workshop for medical students. The students made suggestions for improvements at future workshops (eg, use of free prototype software, shift to e-learning, and more time for group work). Our results can be (and have already been) used as a starting point for future co-design workshops to promote competence-based collaborative learning on digital health topics in medical education.
(©Melina Dederichs, Felix Jan Nitsch, Jennifer Apolinário-Hagen. Originally published in JMIR Medical Education (https://mededu.jmir.org), 10.01.2022.)

Corrosion Casting, Humans, Imaging, Three-Dimensional methods, Technology, X-Ray Microtomography, Artifacts, and Kidney diagnostic imaging

Three-dimensional (3D) printed model of the renal vasculature shows a high level of accuracy of subsequent divisions of both the arterial and the venous tree. However, minor artifacts appeared in the form of oval endings to the terminal branches of the vascular tree, contrary to the anticipated sharply pointed segments. Unfortunately, selective laser sintering process does not currently permit to present the arterial, venous and urinary systems in distinct colors, hence topographic relationship between the vascular and the pelvicalyceal systems is difficult to attain. Nonetheless, the 3D printed model can be used for educational purposes to demonstrate the vast renal vasculature and may also serve as a reference model whilst evaluating morphological anomalies of the intrarenal vasculature in a surgical setting.

Child, Computers, Cone-Beam Computed Tomography, Humans, Transplantation, Autologous, Surgery, Computer-Assisted, and Tooth

Autotransplantation is a surgical technique in which a donor tooth belonging to the same individual is repositioned into a surgically prepared socket or site of previous tooth extraction. It is beneficial in patients with teeth affected by agenesis, trauma, significant caries, and in teeth in a non-restorable condition or prognostically poor due to other pathology. It is particularly useful in paediatric patients, as properly transplanted teeth have a vital periodontium that allows for continuous growth and functional adaptation leading to preservation of the alveolar ridge. Technological advances in rapid prototyping combined with three-dimensional (3D) computed tomography (CT) have the ability to revolutionise autotransplantation. Preoperative planning for atraumatic extraction of the donor tooth and precise preparation of the recipient site with a rapid prototyped surgical template of the donor tooth considerably reduces the extra-alveolar time, and also reduces manipulation of the root sheath and periodontal ligament, and related trauma. This case series demonstrates the efficient and successful autotransplantation of various types of teeth with the use of a rapid prototyped surgical template produced from 3D CT. The use of this technology is expected to refine the surgical technique and improve treatment outcomes.
(Crown Copyright © 2021. Published by Elsevier Ltd. All rights reserved.)

The paper presents an original method concerning the problem of vibration reduction in the general case while milling large-size and geometrically complex details with the use of an innovative approach to the selection of spindle speed. A computational model is obtained by applying the so-called operational approach to identify the parameters of the workpiece modal model. Thanks to the experimental modal analysis results, modal subsystem identification was performed and reliable process data for simulation studies were obtained. Next, simulations of the milling process, for successive values of the spindle speed, are repeated until the best vibration state of the workpiece is obtained. For this purpose, the root mean square values of the time plots of vibration displacements are examined. The effectiveness of the approach proposed for reducing vibrations in the process of face milling is verified on the basis of the results of appropriate experimental investigations. The economic profitability of the implementation of the operational technique in the production practice of enterprises dealing with mechanical processing is demonstrated as well.

Elasticity, Hardness, Materials Testing, Surface Properties, Composite Resins, and Flexural Strength

Objective: This study is focused on testing experimental rapid prototyping materials for occlusal splints made from Urethandimethacrylate (UDMA) and Urethanmethacrylate (UMA).
Methods: Materials were mixed from UDMA and UMA in ratios of 1.0:0.0, 0.75:0.25, 0.5:0.5, 0.25:0.75 and 0.0:1.0. Specimens were printed using digital light processing (DLP). After post-processing, the specimens underwent testing on flexural strength, modulus of elasticity, hardness, wear behavior, surface roughness, gloss and color stability. All tests were performed after 24 h (baseline) and 10 days of water storage (aging). Splints underwent cyclic pull-off and insertion testing, which was alongside simulated using finite element analysis.
Results: The mechanical properties were significantly influenced by changes in the UDMA:UMA ratio. Statistical analysis revealed that increased amounts of UMA correlated with a decrease in flexural strength (92.0 to 30.7 MPa), modulus of elasticity (2.4 to 0.6 GPa), hardness (155.1 to 102.0 N/mm 2 ) and wear resistance (-1394.9 to -1742.1 μm). Materials with higher amounts of UMA were also more likely to be influenced by water storage. Specimens with 75% and 100% UMA content were partly not analyzable due to soft consistency. Optical properties showed only minor influence from UMA content and aging. Differences in surface roughness (3.9 to 2.4 μm) and color stability were insignificant. Gloss was partly influenced by the UDMA:UMA ratio and water storage. Mean survival rates for cyclic pull-off and insertion testing ranged from 2537 to 23,857 cycles. A correlation between the amount of UMA and survival rates was observed.
Significance: The addition of up to 25% UMA showed promising results, complying with clinical standards and delivering acceptable results in the cyclic pull-off and insertion test. Further investigation on increments between 0 and 25% UMA could help to find an optimum.
(Copyright © 2021 The Academy of Dental Materials. Published by Elsevier Inc. All rights reserved.)