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Keywords: ab initio; electronic structure; FANCI; method development; Python Abstract 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. Article Note: Funding information Canada Research Chairs; Natural Sciences and Engineering Research Council of Canada; CANARIE; Compute Canada; Research Board of Ghent University; University of Florida Byline: Taewon D. Kim, M. Richer, Gabriela Sánchez-Díaz, Ramón Alain Miranda-Quintana, Toon Verstraelen, Farnaz Heidar-Zadeh, Paul W. Ayers

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.)

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.)

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).)

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.)

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.)

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, 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.)

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.

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.

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.)

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.)

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.

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.

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.

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).)

Implant dentures -- Methods, Implant dentures -- Usage, Rapid prototyping -- Methods, and Rapid prototyping -- Usage

To purchase or authenticate to the full-text of this article, please visit this link: http://onlinelibrary.wiley.com/doi/10.1002/rcs.1895/abstract Byline: Mohamed Farid Shehab, Nabila Mohammed Abdel Hamid, Nevien Abdullatif Askar, Ahmed Mokhtar Elmardenly Keywords: CAD-CAM, electron beam melting; immediate mandibular reconstruction; patient-specific titanium mesh; rapid prototyping Abstract Background Immediate mandibular reconstruction was performed using a patient-specific titanium mesh tray fabricated by electron beam melting (EBM) /rapid prototyping techniques. Methods Patient-specific titanium trays were virtually designed and fabricated using EBM technology/rapid prototyping for patients requiring mandibular resection and immediate reconstruction using an iliac crest bone graft. Dental implants were placed in the grafted sites and the patients received prosthetic rehabilitation with a follow-up of one year. Clinical data, postoperative bone formation and complications were evaluated. Results A symmetric appearance of facial contours was achieved. The titanium tray incorporated the particulate iliac crest bone graft that provided significant bone formation (mean 18.97 [+ or -] 1.45 mm) and predictable results. Stability of the dental implants was achieved. Conclusion The patient-specific titanium meshes and immediate particulate autogenous bone graft showed satisfactory clinical and surgical results in improving patients' quality of life and decreasing the overall treatment time with adequate functional rehabilitation.

Algorithms -- Analysis and Algorithm

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.)

Teaching -- Usage, Teaching -- Methods, and Teaching -- Study and teaching

Given the ubiquity of interfaces on computing devices, it is essential for future Information Systems (IS) professionals to understand the ramifications of good user interface (UI) design. This article provides instructions on how to efficiently and effectively teach IS students about "fit," a Human-Computer Interaction (HCI) concept, through a paper prototyping activity. Although easy to explain, the concept of "fit" can be difficult to understand without repeated practice. Practically, designing "fit" into UIs can be cost-prohibitive because working prototypes are often beyond students' technical skillset. Accordingly, based on principles of active learning, we show how to use paper prototyping to demonstrate "fit" in a hands-on class exercise. We provide detailed stepby-step instructions to plan, setup, and present the exercise to guide students through the process of "fit" in UI design. As a result of this activity, students are better able to employ both theoretical and practical applications of "fit" in UI design and implementation. This exercise is applicable in any course that includes UI design, such as principles of HCI, systems analysis and design, software engineering, and project management. Keywords: Human-computer interaction (HCI), Paper prototyping, Active learning, Constructionism, Teaching tip
1. INTRODUCTION With computing devices peppering nearly every aspect of our lives, how people interact with these technologies is critically important to all computing fields. In fact, failure to properly [...]

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.)

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.

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).)