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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.)

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/V pp far-field transmitting sensitivity with 25.3% fractional bandwidth whereas the type B transducer showed 2.1 kPa/V pp 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.

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.)

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).)

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).)

Humans, Vertical Dimension, Composite Resins, Dental Occlusion, Denture, Partial, Removable, Anodontia, Mouth, Edentulous, and Jaw, Edentulous, Partially

Full-mouth rehabilitation can be challenging due to the complexity of restoring the vertical dimension of occlusion (VDO) and replacing missing teeth. In partially edentulous patients, the concept of a bonded composite resin prototype for increasing the VDO has previously been applied through the use of an overlay removable partial denture (RPD) with acrylic resin covering the existing dentition. Unfortunately, this type of prosthesis does not always accurately model the function and phonetics intended for the definitive prostheses, and the esthetic result often is less than ideal. It would be advantageous if direct bonding could be used with the patient's existing RPD to model the increased VDO, but this approach has not been reported in the literature. This case report describes the direct bonding of an existing RPD to create a prototype for increased VDO in a partially edentulous patient with a skeletal Class II malocclusion. The successful outcome has been maintained for more than 1 year.
Competing Interests: No conflicts of interest reported.

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.

Pattern Recognition, Automated, Computer Graphics, Algorithms, Hand, Gestures, and Augmented Reality

In this paper we examine the task of key gesture spotting: accurate and timely online recognition of hand gestures. We specifically seek to address two key challenges faced by developers when integrating key gesture spotting functionality into their applications. These are: i) achieving high accuracy and zero or negative activation lag with single-time activation; and ii) avoiding the requirement for deep domain expertise in machine learning. We address the first challenge by proposing a key gesture spotting architecture consisting of a novel gesture classifier model and a novel single-time activation algorithm. This key gesture spotting architecture was evaluated on four separate hand skeleton gesture datasets, and achieved high recognition accuracy with early detection. We address the second challenge by encapsulating different data processing and augmentation strategies, as well as the proposed key gesture spotting architecture, into a graphical user interface and an application programming interface. Two user studies demonstrate that developers are able to efficiently construct custom recognizers using both the graphical user interface and the application programming interface.

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.)

Fanpy is a free and open-source Python library for developing and testing multideterminant wavefunctions and related ab initio methods in electronic structure theory. The main use of Fanpy is to quickly prototype new methods by making it easier to convert the mathematical formulation of a new wavefunction ansätze to a working implementation. Fanpy is designed based on our recently introduced Flexible Ansatz for N-electron Configuration Interaction (FANCI) framework, where multideterminant wavefunctions are represented by their overlaps with Slater determinants of orthonormal spin-orbitals. In the simplest case, a new wavefunction ansatz can be implemented by simply writing a function for evaluating its overlap with an arbitrary Slater determinant. Fanpy is modular in both implementation and theory: the wavefunction model, the system's Hamiltonian, and the choice of objective function are all independent modules. This modular structure makes it easy for users to mix and match different methods and for developers to quickly explore new ideas. Fanpy is written purely in Python with standard dependencies, making it accessible for various operating systems. In addition, it adheres to principles of modern software development, including comprehensive documentation, extensive testing, quality assurance, and continuous integration and delivery protocols. This article is considered to be the official release notes for the Fanpy library.
(© 2022 Wiley Periodicals LLC.)

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.