articles+ search results

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.

Purpose: Virtual reality (VR) can provide an added value for diagnosis and/or intervention planning. Several VR software implementations have been proposed but they are often application dependent. Previous attempts for a more generic solution incorporating VR in medical prototyping software (MeVisLab) were still lacking functionality precluding easy and flexible development.
Methods: We propose an alternative solution that uses rendering to a graphical processing unit (GPU) texture to enable rendering arbitrary Open Inventor scenes in a VR context. It facilitates flexible development of user interaction and rendering of more complex scenes involving multiple objects. We tested the platform in planning a transcatheter cardiac stent placement procedure.
Results: This approach proved to enable development of a particular implementation that facilitates planning of percutaneous treatment of a sinus venosus atrial septal defect. The implementation showed it is intuitive to plan and verify the procedure using VR.
Conclusion: An alternative implementation for linking OpenVR with MeVisLab is provided that offers more flexible development of VR prototypes which can facilitate further clinical validation of this technology in various medical disciplines.
(© 2022. CARS.)

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).)

The use of personal protective equipment (PPE) has become essential to reduce the transmission of coronavirus disease 2019 (COVID-19) as it prevents the direct contact of body fluid aerosols expelled from carriers. However, many countries have reported critical supply shortages due to the spike in demand during the outbreak in 2020. One potential solution to ease pressure on conventional supply chains is the local fabrication of PPE, particularly face shields, due to their simplistic design. The purpose of this paper is to provide a research protocol and cost implications for the rapid development and manufacturing of face shields by individuals or companies with minimal equipment and materials. This article describes a best practice case study in which the establishment of a local manufacturing hub resulted in the swift production of 12,000 face shields over a seven-week period to meet PPE shortages in the North-West region of Ireland. Protocols and processes for the design, materials sourcing, prototyping, manufacturing, and distribution of face shields are described. Three types of face shields were designed and manufactured, including Flat, Laser-cut, and 3D-printed models. Of the models tested, the Flat model proved the most cost-effective (€0.51/unit), while the Laser-cut model was the most productive (245 units/day). The insights obtained from this study demonstrate the capacity for local voluntary workforces to be quickly mobilised in response to a healthcare emergency, such as the COVID-19 pandemic.
(© 2022 The Authors.)

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.

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 Ep = 91.3 mV, Ipa / Ipc = 0.905, characterized by cyclic voltammetry using a standard ferrocyanide redox probe, and this was compared against a commercial screen-printed gold electrode (Δ Ep = 68.9 mV, Ipa / Ipc = 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.

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.
(Copyright © 2022 Dragusanu, Troisi, Villani, Prattichizzo and Malvezzi.)

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).)

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.)

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).

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

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

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

We demonstrate the ability to rapidly prototype and fabricate an epoxy-embedded electrode platform and microfluidic device suitable for using electrochemical biosensors under flow conditions. We utilize three-dimensional (3-D) printing to rapidly prototype molds to fabricate epoxy-embedded electrodes in addition to molds for rapid prototyping of PDMS microfluidic components. We characterize the bare gold epoxy-embedded electrodes using ferricyanide as a redox indicator and then characterize the performance of an adenosine triphosphate (ATP) specific electrochemical, aptamer-based (E-AB) sensor. We then incorporate the ATP specific E-AB sensors into the microfluidic device to study and take advantage of the dynamic response this class of sensor offers. We were able to flow varying concentrations of target analyte and monitor the dynamic response of the sensors to the changing concentration. This work demonstrates the ability to rapidly prototype E-AB sensors under flow conditions using 3-D printing which can lead to rapid and affordable point-of-care or fieldable applications where dynamic measurements of concentration, specificity and sensitivity and multiplex detection are necessary.
(Copyright © 2021 Elsevier B.V. All rights reserved.)

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

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

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

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

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

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

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.

As telecommunications technology progresses, telehealth frameworks are becoming more widely adopted in the context of long-term care (LTC) for older adults, both in care facilities and in homes. Today, robots could assist healthcare workers when they provide care to elderly patients, who constitute a particularly vulnerable population during the COVID-19 pandemic. Previous work on user-centered design of assistive technologies in LTC facilities for seniors has identified positive impacts. The need to deal with the effects of the COVID-19 pandemic emphasizes the benefits of this approach, but also highlights some new challenges for which robots could be interesting solutions to be deployed in LTC facilities. This requires customization of telecommunication and audio/video/data processing to address specific clinical requirements and needs. This paper presents OpenTera, an open source telehealth framework, aiming to facilitate prototyping of such solutions by software and robotic designers. Designed as a microservice-oriented platform, OpenTera is an end-to-end solution that employs a series of independent modules for tasks such as data and session management, telehealth, daily assistive tasks/actions, together with smart devices and environments, all connected through the framework. After explaining the framework, we illustrate how OpenTera can be used to implement robotic solutions for different applications identified in LTC facilities and homes, and we describe how we plan to validate them through field trials.
(© The Author(s) under exclusive licence to International Union for Physical and Engineering Sciences in Medicine (IUPESM) 2022.)

Cell-Free System metabolism, Metabolic Networks and Pathways, Protein Biosynthesis, Biosynthetic Pathways, and Metabolic Engineering methods

Biological systems provide a sustainable and complimentary approach to synthesizing useful chemical products. Metabolic engineers seeking to establish economically viable biosynthesis platforms strive to increase product titers, rates, and yields. Despite continued advances in genetic tools and metabolic engineering techniques, cellular workflows remain limited in throughput. It may take months to test dozens of unique pathway designs even in a robust model organism, such as Escherichia coli. In contrast, cell-free protein synthesis enables the rapid generation of enzyme libraries that can be combined to reconstitute metabolic pathways in vitro for biochemical synthesis in days rather than weeks. Cell-free reactions thereby enable comparison of hundreds to thousands of unique combinations of enzyme homologs and concentrations, which can quickly identify the most productive pathway variants to test in vivo or further characterize in vitro. This cell-free pathway prototyping strategy provides a complementary approach to accelerate cellular metabolic engineering efforts toward highly productive strains for metabolite production.
(© 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

The strategy of embedding conductive materials on polymeric matrices has produced functional and wearable artificial electronic skin prototypes capable of transduction signals, such as pressure, force, humidity, or temperature. However, these prototypes are expensive and cover small areas. This study proposes a more affordable manufacturing strategy for manufacturing conductive layers with 6 × 6 matrix micropatterns of RTV-2 silicone rubber and Single-Walled Carbon Nanotubes (SWCNT). A novel mold with two cavities and two different micropatterns was designed and tested as a proof-of-concept using Low-Force Stereolithography-based additive manufacturing (AM). The effect SWCNT concentrations (3 wt.%, 4 wt.%, and 5 wt.%) on the mechanical properties were characterized by quasi-static axial deformation tests, which allowed them to stretch up to ~160%. The elastomeric soft material's hysteresis energy (Mullin's effect) was fitted using the Ogden-Roxburgh model and the Nelder-Mead algorithm. The assessment showed that the resulting multilayer material exhibits high flexibility and high conductivity (surface resistivity ~7.97 × 10 4 Ω/sq) and that robust soft tooling can be used for other devices.

Industry, Lakes, and Software

Seaports are genuine, intermodal hubs connecting seaways to inland transport links, such as roads and railways. Seaports are located at the focal point of institutional, industrial, and control activities in a jungle of interconnected information systems. System integration is setting considerable challenges when a group of independent providers are asked to implement complementary software functionalities. For this reason, seaports are the ideal playground where software is highly composite and tailored to a large variety of final users (from the so-called port communities). Although the target would be that of shaping the Port Authorities to be providers of (digital) innovation services, the state-of-the-art is still that of considering them as final users, or proxies of them. For this reason, we show how a canonical cloud, virtualizing a distributed architecture, can be structured to host different, possibly overlapped, tenants, slicing the information system at the infrastructure, platform, and software layers. Resources at the infrastructure and platform layers are shared so that a variety of independent applications can make use of the local calculus and access the data stored in a Data Lake. Such a cloud is adopted by the Port of Livorno as a rapid prototyping framework for the development and deployment of ICT innovation services. In order to demonstrate the versatility of this framework, three case studies relating to as many prototype ICT services (Navigation Safety, e-Freight, and Logistics) released within three industrial tenants are here presented and discussed.

Organ-on-a-chip (OoC) and microfluidic devices are conventionally produced using microfabrication procedures that require cleanrooms, silicon wafers, and photomasks. The prototyping stage often requires multiple iterations of design steps. A simplified prototyping process could therefore offer major advantages. Here, we describe a rapid and cleanroom-free microfabrication method using maskless photolithography. The approach utilizes a commercial digital micromirror device (DMD)-based setup using 375 nm UV light for backside exposure of an epoxy-based negative photoresist (SU-8) on glass coverslips. We show that microstructures of various geometries and dimensions, microgrooves, and microchannels of different heights can be fabricated. New SU-8 molds and soft lithography-based polydimethylsiloxane (PDMS) chips can thus be produced within hours. We further show that backside UV exposure and grayscale photolithography allow structures of different heights or structures with height gradients to be developed using a single-step fabrication process. Using this approach: (1) digital photomasks can be designed, projected, and quickly adjusted if needed; and (2) SU-8 molds can be fabricated without cleanroom availability, which in turn (3) reduces microfabrication time and costs and (4) expedites prototyping of new OoC devices.

Aged, Communication, Humans, Motivation, Quality of Life, Aphasia, and Mobile Applications

Aphasia is a partial or total loss of the ability to articulate ideas or comprehend spoken language, resulting from brain damage, in a person whose language skills were previously normal. Our goal was to find out how a storytelling app can help people with aphasia to communicate and share daily experiences. For this purpose, the Aphasia Create app was created for tablets, along with Aphastory for the Google Glass device. These applications facilitate social participation and enhance quality of life by using visual storytelling forms composed of photos, drawings, icons, etc., that can be saved and shared. We performed usability tests (supervised by a neuropsychologist) on six participants with aphasia who were able to communicate. Our work contributes (1) evidence that the functions implemented in the Aphasia Create tablet app suit the needs of target users, but older people are often not familiar with tactile devices, (2) reports that the Google Glass device may be problematic for persons with right-hand paresis, and (3) a characterization of the design guidelines for apps for aphasics. Both applications can be used to work with people with aphasia, and can be further developed. Aphasic centers, in which the apps were presented, expressed interest in using them to work with patients. The Aphasia Create app won the Enactus Poland National Competition in 2015.

Many New Zealand residential dwellings suffer from dampness and fungi during the winter, which can cause respiratory health problems. This can be due to poor insulation and ventilation, and the situation worsens when residents cannot afford to heat the dwelling. The main aim of this paper is to modify an existing dehumidifier so that it can remove moisture, heat the living space and reduce fungi growth and bacteria. To achieve that, we installed ultraviolet germicidal lights (UVGI) in an existing dehumidifier with a total cost of USD $150.7 (NZD $213.76). The UVGI lights are known to be efficient in destroying the DNA of fungi and bacteria. The results show that the device reduced the fungi growth and did increase the room temperature because the dehumidifier captured two litres of water over 24 h of testing. The proposed device did achieve a reduction in particulate matters, from 0.9μg/m3to 0.14μg/m3and an acceptable range of relative humidity below 50%, which reduces the favourable conditions for fungi growth. Therefore, our proposed low-cost device does improve the indoor air quality (IAQ) in the living space.
(© 2021 The Author(s).)

Cell Culture Techniques, Humans, Reproducibility of Results, Xylenes, Lab-On-A-Chip Devices, and Polymers

Fabrication of microfluidic devices by photolithography generally requires specialized training and access to a cleanroom. As an alternative, 3D printing enables cost-effective fabrication of microdevices with complex features that would be suitable for many biomedical applications. However, commonly used resins are cytotoxic and unsuitable for devices involving cells. Furthermore, 3D prints are generally refractory to elastomer polymerization such that they cannot be used as master molds for fabricating devices from polymers ( e.g. polydimethylsiloxane, or PDMS). Different post-print treatment strategies, such as heat curing, ultraviolet light exposure, and coating with silanes, have been explored to overcome these obstacles, but none have proven universally effective. Here, we show that deposition of a thin layer of parylene, a polymer commonly used for medical device applications, renders 3D prints biocompatible and allows them to be used as master molds for elastomeric device fabrication. When placed in culture dishes containing human neurons, regardless of resin type, uncoated 3D prints leached toxic material to yield complete cell death within 48 hours, whereas cells exhibited uniform viability and healthy morphology out to 21 days if the prints were coated with parylene. Diverse PDMS devices of different shapes and sizes were easily cast from parylene-coated 3D printed molds without any visible defects. As a proof-of-concept, we rapid prototyped and tested different types of PDMS devices, including triple chamber perfusion chips, droplet generators, and microwells. Overall, we suggest that the simplicity and reproducibility of this technique will make it attractive for fabricating traditional microdevices and rapid prototyping new designs. In particular, by minimizing user intervention on the fabrication and post-print treatment steps, our strategy could help make microfluidics more accessible to the biomedical research community.

Chromatography, Liquid, Drug Liberation, Humans, Printing, Three-Dimensional, Tandem Mass Spectrometry, and Technology, Pharmaceutical

Analytical sample preparation techniques are regarded as crucial steps for analyzing compounds from different biological matrices. The development of new extraction techniques is a modern trend in the bioanalytical sciences. 3D printed techniques have emerged as a valuable technology for prototyping devices in customized shapes for a cost-effective way to advance analytical sample preparation techniques. The present study aims to fabricate customized filaments through the hot-melt extrusion (HME) technique followed by fused deposition modeling mediated 3D printing process for rapid prototyping of 3D printed sorbents to extract a sample from human plasma. Thus, we fabricated our own indigenous filament using poly (vinyl alcohol), Eudragit® RSPO, and tri-ethyl citrate through HME to prototype the fabricated filament into a 3D printed sorbent for the extraction of small molecules. The 3D sorbent was applied to extract hydrocortisone from human plasma and analyzed using a validated LC-MS/MS method. The extraction procedure was optimized, and the parameters influencing the sorbent extraction were systematically investigated. The extraction recovery of hydrocortisone was found to be >82% at low, medium, and high quality control samples, with a relative standard deviation of <2%. The intra-and inter-day precisions for hydrocortisone ranged from 1.0% to 12% and 2.0%-10.0%, respectively, whereas the intra-and inter-day accuracy for hydrocortisone ranged from 93.0% to 111.0% and 92.0% to 110.0%, respectively. The newly customizable size and shape of the 3D printed sorbent opens new possibilities for extracting small molecules from human plasma.
(Copyright © 2021 Elsevier B.V. All rights reserved.)

Cadaver, Cervical Vertebrae diagnostic imaging, Cervical Vertebrae surgery, Humans, Pedicle Screws, Spinal Fusion, and Surgery, Computer-Assisted

Purpose: Due to the high perforation rate of cervical pedicle screw placement, we have designed four different types of rapid prototyping navigation templates to enhance the accuracy of cervical pedicle screw placement.
Methods: Fifteen human cadaveric cervical spines from C2 to C7 were randomly divided into five groups, with three specimens in each group. The diameter of pedicle screw used in this study was 3.5 mm. Groups 1-4 were assisted by the two-level template, one-level bilateral template, one-level unilateral template and one-level point-contact template, respectively. Group 5 was without any navigation template. After the surgery, the accuracy of screw placement in the five groups was evaluated using postoperative computed tomographic scans to observe whether the screw breached the pedicle cortex.
Results: A total of 180 pedicle screws were inserted without any accidents. The accuracy rate was 75%, 100%, 100%, 91.7%, and 63.9%, respectively, from Groups 1 to 5. All the template groups were significantly higher than Group 5, though the two-level navigation template group was significantly lower than the other three template groups. The operation time was 4.72 ± 0.28, 4.81 ± 0.29, 5.03 ± 0.35, 8.42 ± 0.36, and 10.05 ± 0.52 min, respectively, from Groups 1 to 5. The no template and point-contact procedures were significantly more time-consuming than the template procedures.
Conclusion: This study demonstrated that four different design types of navigation templates achieved a higher accuracy in assisting cervical pedicle screw placement than no template insertion. However, the two-level template's accuracy was the lowest compared to the other three templates. Meanwhile, these templates avoided fluoroscopy during the surgery and decreased the operation time. It is always very challenging to translate cadaveric studies to clinical practice. Hence, the one-level bilateral, unilateral, and point-contact navigation templates designed by us need to be meticulously tested to verify their accuracy and safety.

LoRaWAN has gained significant attention for Internet-of-Things (IOT) applications due to its low power consumption and long range potential for data transmission. While there is a significant body of work assessing LoRA coverage and data transmission characteristics, there is a lack of data available about commercially available LoRa prototyping boards and their power consumption, in relation to their features. It is currently difficult to estimate the power consumption of a LoRa module operating under different transmission profiles, due to a lack of manufacturer data available. In this study, power testing has been carried out on physical hardware and significant variation was found in the power consumption of competing boards, all marketed as "extremely low power". In this paper, testing results are presented alongside an experimentally-derived power model for the lowest power LoRa module, and power requirements are compared to firmware settings. The power analysis adds to existing work showing trends in data-rate and transmission power settings effects on electrical power consumption. The model's accuracy is experimentally verified and shows acceptable agreement to estimated values. Finally, applications for the model are presented by way of a hypothetical scenario and calculations performed in order to estimate battery life and energy consumption for varying data transmission intervals.

The work describes a fast and flexible micro/nano fabrication and manufacturing method for ceramic Micro-electromechanical systems (MEMS)sensors. Rapid prototyping techniques are demonstrated for metal oxide sensor fabrication in the form of a complete MEMS device, which could be used as a compact miniaturized surface mount devices package. Ceramic MEMS were fabricated by the laser micromilling of already pre-sintered monolithic materials. It has been demonstrated that it is possible to deposit metallization and sensor films by thick-film and thin-film methods on the manufactured ceramic product. The results of functional tests of such manufactured sensors are presented, demonstrating their full suitability for gas sensing application and indicating that the obtained parameters are at a level comparable to those of industrial produced sensors. Results of design and optimization principles of applied methods for micro- and nanosystems are discussed with regard to future, wider application in semiconductor gas sensors prototyping.

Carbon dioxide (CO 2 )-laser processing of glasses is a versatile maskless writing technique to engrave micro-structures with flexible control on shape and size. In this study, we present the fabrication of hundreds of microns quartz micro-channels and micro-holes by pulsed CO 2 -laser ablation with a focus on the great potential of the technique in microfluidics and biomedical applications. After discussing the impact of the laser processing parameters on the design process, we illustrate specific applications. First, we demonstrate the use of a serpentine microfluidic reactor prepared by combining CO 2 -laser ablation and post-ablation wet etching to remove surface features stemming from laser-texturing that are undesirable for channel sealing. Then, cyclic olefin copolymer micro-pillars are fabricated using laser-processed micro-holes as molds with high detail replication. The hundreds of microns conical and square pyramidal shaped pillars are used as templates to drive 3D cell assembly. Human Umbilical Vein Endothelial Cells are found to assemble in a compact and wrapping way around the micro-pillars forming a tight junction network. These applications are interesting for both Lab-on-a-Chip and Organ-on-a-Chip devices.
(© 2021 The Authors.)

Area Under Curve, Clinical Trials as Topic, Drug Therapy, Combination methods, Humans, Precision Medicine methods, Remission Induction, Treatment Outcome, Antidepressive Agents therapeutic use, Clinical Decision-Making methods, Deep Learning, Depression drug therapy, and Depressive Disorder, Major drug therapy

Machine-assisted treatment selection commonly follows one of two paradigms: a fully personalized paradigm which ignores any possible clustering of patients; or a sub-grouping paradigm which ignores personal differences within the identified groups. While both paradigms have shown promising results, each of them suffers from important limitations. In this article, we propose a novel deep learning-based treatment selection approach that is shown to strike a balance between the two paradigms using latent-space prototyping. Our approach is specifically tailored for domains in which effective prototypes and sub-groups of patients are assumed to exist, but groupings relevant to the training objective are not observable in the non-latent space. In an extensive evaluation, using both synthetic and Major Depressive Disorder (MDD) real-world clinical data describing 4754 MDD patients from clinical trials for depression treatment, we show that our approach favorably compares with state-of-the-art approaches. Specifically, the model produced an 8% absolute and 23% relative improvement over random treatment allocation. This is potentially clinically significant, given the large number of patients with MDD. Therefore, the model can bring about a much desired leap forward in the way depression is treated today.

We have developed a rapid prototyping approach for creating custom grating magneto-optical traps using a dual-beam system combining a focused ion beam and a scanning electron microscope. With this approach we have created both one- and two-dimensional gratings of up to 400 µm × 400 µm in size with structure features down to 100 nm, periods of 620 nm, adjustable aspect ratios (ridge width : depth ∼ 1 : 0.3 to 1 : 1.4) and sidewall angles up to 71°. The depth and period of these gratings make them suitable for holographic trapping and cooling of neutral ytterbium on the 1 S 0 → 1 P 1 399 nm transition. Optical testing of the gratings at this wavelength has demonstrated a total first order diffraction of 90% of the reflected light. This work therefore represents a fast, high resolution, programmable and maskless alternative to current photo and electron beam lithography-based procedures and provides a time efficient process for prototyping of small period, high aspect ratio grating magneto-optical traps and other high resolution structures.

Integrated microfluidic biosensors enable powerful microscale analyses in biology, physics, and chemistry. However, conventional methods for fabrication of biosensors are dependent on cleanroom-based approaches requiring facilities that are expensive and are limited in access. This is especially prohibitive toward researchers in low- and middle-income countries. In this topical review, we introduce a selection of state-of-the-art, low-cost prototyping approaches of microfluidics devices and miniature sensor electronics for the fabrication of sensor devices, with focus on electrochemical biosensors. Approaches explored include xurography, cleanroom-free soft lithography, paper analytical devices, screen-printing, inkjet printing, and direct ink writing. Also reviewed are selected surface modification strategies for bio-conjugates, as well as examples of applications of low-cost microfabrication in biosensors. We also highlight several factors for consideration when selecting microfabrication methods appropriate for a project. Finally, we share our outlook on the impact of these low-cost prototyping strategies on research and development. Our goal for this review is to provide a starting point for researchers seeking to explore microfluidics and biosensors with lower entry barriers and smaller starting investment, especially ones from low resource settings.
(© 2021 Author(s).)

Adult, Female, Humans, Male, Pregnancy, Sexual Partners, South Africa, Viral Load, HIV Infections diagnosis, HIV Infections drug therapy, and HIV Testing

Daily antiretroviral therapy (ART) suppresses viral replication, rendering HIV undetectable through viral load (VL) testing. People living with HIV (PLWH) who have an undetectable VL cannot transmit HIV to sexual partners or through giving birth, a message commonly referred to as U = U (undetectable equals untransmittable). To increase knowledge and understanding of U = U among men, who have poorer HIV testing and treatment outcomes than women, we engaged men from high HIV burden communities in Cape Town in two interactive human-centered design cocreation workshops to develop local U = U messaging for men. Two trained workshop facilitators, explained the U = U message to 39 adult men (in two separate workshops), and asked them how to effectively communicate U = U to other men in the local language (isiXhosa). Participant-designed messages sought to inform men about U = U to help assuage fears of testing HIV positive (by removing the stigma of living with HIV and being a vector of disease), and to explain that ART enables PLWH to live normal healthy lives, making HIV "untransmittable" to sex partners. Participants' messages emphasized that when virally suppressed, " I cannot spread HIV to the other person " and " (the pill) keeps on killing the virus so I can live a normal life for the rest of my life. " Men cocreated simple local U = U messages to address fears of testing HIV positive and emphasizing ART's positive effects. Cocreated tailored messaging may reduce stigma associated with living with HIV and improve the uptake of HIV testing and treatment among South African men. This study was registered at clinicaltrials.gov under NCT04364165.

Humans, Artificial Limbs, and Laboratories

We present a network-enabled myoelectric platform for performing research outside of the laboratory environment. A low-cost, flexible, modular design based on common Internet of Things connectivity technology allows home-based research to be piloted. An outline of the platform is presented followed by technical results obtained from ten days of home-based tests with three participants. Results show the system enabled collection of close to 12,000 trials during around 28 cumulative hours of use. Home-based testing of multiple participants in parallel offers efficiency gains and provides a intuitive route toward long-term testing of upper-limb prosthetic devices in more naturalistic settings.Clinical relevance- In-home myoelectric training reduces clinician time. Network-enabled systems with back-end dashboards allow clinicians to monitor patients myoelectric ability over time and will provide a new way of accessing information about how upper-limb prosthetics are commonly used.

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

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

Humans, Prospective Studies, Radiography, Tomography, X-Ray Computed, Acetabulum diagnostic imaging, Acetabulum surgery, Arthroplasty, Replacement, Hip methods, Printing, Three-Dimensional, Prosthesis Failure, and Reoperation methods

Objective: To compare rapid prototyping technology (RP tech) in revision total hip arthroplasty (RTHA) with traditional examination methods and to see how they are different in evaluating acetabular anatomy and designing surgical procedure.
Methods: From February 2014 to March 2018, 43 RTHA patients with complex acetabulum defects were enrolled in this prospective study regardless of age or gender. Incomplete and unclear data were excluded. Three types of radiographic examination were performed on each patient before the revision surgery. Four groups of evaluations were designed: (i) X-ray; (ii) computed tomography (CT-scan); (iii) RP tech; and (iv) CT-aided RP tech. Discrepancies between preoperative radiographic analysis and intra-operative findings were separately compared by a team of surgeons. Premade surgical plans based on each evaluation method were compared with the final surgical procedure. The compliance of anatomic evaluation and surgical plan-design based on 3D RP tech and traditional radiographs were ranked manually by a of team surgeons into: (i) complete accordance; (ii) general accordance; and (iii) undetermined structure/procedure. The difference in ranks between RP tech and traditional radiographic methods were analyzed with a nonparametric Kruskal-Wallis test. P < 0.05 was considered significant. Multiple adjustments were taken for the statistical tests level according to the Bonferroni method.
Results: For anatomic analysis, the accordance in four groups of evaluating methods differed from each other (P < 0.05) except for the comparison of RP tech and CT-aided RP tech. RP tech displayed better anatomic evaluating accuracy than traditional methods (X-ray and CT) with the "complete accordance" rates of these groups being 88.37%, 4.65% and 27.91%, respectively. But CT-aided RP tech did not improve accuracy significantly compared with using RP tech individually, although the value seems high in the CT-aided RP group with the "complete accordance" rate of 95.35%. For surgery design, RP tech significantly showed better applicable surgical design compared with X-ray and CT (P < 0.05), and the "complete accordance" rates were 88.37%, 6.98% and 23.26%, but no significant difference was observed between RP tech and CT-aided RP tech, and the "complete accordance" rate of CT-aided RP tech group was 97.67%. RP tech showed remarkable improvement in bone defect assessment and surgical plan design.
Conclusion: Using RP technology improved both sensibility and accuracy in acetabular defect evaluation with better locating and evaluating efficiency compared with X-ray and CT-scans. It also improved surgical schedule designing in complex acetabular defecting revision surgery. In particularly complex cases, CT aided RP tech may increase the accuracy of RP tech.
(© 2021 The Authors. Orthopaedic Surgery published by Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

Heart, Humans, Pilot Projects, Tomography, X-Ray Computed, Models, Anatomic, and Printing, Three-Dimensional

Introduction: Rapid prototyping is a process by which three-dimensional (3D) computerized surface models are converted into physical models. In this study, a 3D heart bio model was created using the rapid prototyping method and the accuracy of this heart model was assessed by clinicians.
Methods: The two-dimensional images of normal heart from gated computed tomography scan datasets were used to create a 3D model of the heart. The slices were then processed using the software BioModroid and printed with the 3D printer. The evaluation of the model was performed by a questionnaire answered by four cardiothoracic surgeons, 12 cardiologists, five radiologists, and nine surgical registrars.
Results: Eighty-six percent of the anatomy structures showed in this model scored 100% accuracy. Structures such as circumflex branch of left coronary artery, great cardiac vein, papillary muscle, and coronary sinus were each rated 77%, 70%, 70%, and 57% accurate. Among 30 clinicians, a total of 93% rated the model accuracy as good and above; 64% of the clinicians evaluated this model as an excellent teaching tool for anatomy class. As a visual aid for surgery or interventional procedures, the model was rated excellent (40%), good (50%), average (23%), and poor (3%); 70% of the clinicians scored the model as above average for training purpose. Overall, this 3D rapid prototyping cardiac model was rated as excellent (33%), good (50%), and average (17%).
Conclusion: This 3D rapid prototyping heart model will be a valuable source of anatomical education and cardiac interventional management.

Nucleic Acid Conformation, DNA chemistry, Gold chemistry, Metal Nanoparticles chemistry, Nanostructures chemistry, Nanotechnology methods, and Software

Wireframe DNA origami assemblies can now be programmed automatically from the top-down using simple wireframe target geometries, or meshes, in 2D and 3D, using either rigid, six-helix bundle (6HB) or more compliant, two-helix bundle (DX) edges. While these assemblies have numerous applications in nanoscale materials fabrication due to their nanoscale spatial addressability and high degree of customization, no easy-to-use graphical user interface software yet exists to deploy these algorithmic approaches within a single, standalone interface. Further, top-down sequence design of 3D DX-based objects previously enabled by DAEDALUS was limited to discrete edge lengths and uniform vertex angles, limiting the scope of objects that can be designed. Here, we introduce the open-source software package ATHENA with a graphical user interface that automatically renders single-stranded DNA scaffold routing and staple strand sequences for any target wireframe DNA origami using DX or 6HB edges, including irregular, asymmetric DX-based polyhedra with variable edge lengths and vertices demonstrated experimentally, which significantly expands the set of possible 3D DNA-based assemblies that can be designed. ATHENA also enables external editing of sequences using caDNAno, demonstrated using asymmetric nanoscale positioning of gold nanoparticles, as well as providing atomic-level models for molecular dynamics, coarse-grained dynamics with oxDNA, and other computational chemistry simulation approaches.
(© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.)

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.

Computer Simulation, Feedback, Physiological radiation effects, Gene Expression Regulation radiation effects, Light, Saccharomyces cerevisiae genetics, Saccharomyces cerevisiae physiology, Saccharomyces cerevisiae radiation effects, Gene Expression Regulation genetics, Optogenetics methods, Single-Cell Analysis methods, Stochastic Processes, and Synthetic Biology methods

The design and implementation of synthetic circuits that operate robustly in the cellular context is fundamental for the advancement of synthetic biology. However, their practical implementation presents challenges due to low predictability of synthetic circuit design and time-intensive troubleshooting. Here, we present the Cyberloop, a testing framework to accelerate the design process and implementation of biomolecular controllers. Cellular fluorescence measurements are sent in real-time to a computer simulating candidate stochastic controllers, which in turn compute the control inputs and feed them back to the controlled cells via light stimulation. Applying this framework to yeast cells engineered with optogenetic tools, we examine and characterize different biomolecular controllers, test the impact of non-ideal circuit behaviors such as dilution on their operation, and qualitatively demonstrate improvements in controller function with certain network modifications. From this analysis, we derive conditions for desirable biomolecular controller performance, thereby avoiding pitfalls during its biological implementation.
(© 2021. The Author(s).)

Polymerization, Printing, Three-Dimensional, Tissue Engineering, Tissue Scaffolds, and Bioprinting

Bioprinting is an attractive technology for building tissues from scratch to explore entire new cell configurations, which brings numerous opportunities for biochemical research such as engineering tissues for therapeutic tissue repair or drug screening. However, bioprinting is faced with the limited number of suitable bioinks that enable bioprinting with excellent printability, high structural fidelity, physiological stability, and good biocompatibility, particularly in the case of extrusion-based bioprinting. Herein, we demonstrate a composite bioink based on gelatin, bacterial cellulose (BC), and microbial transglutaminase (mTG enzyme) with outstanding printing controllability and durable architectural integrity. BC, as a rheology modifier and mechanical enhancer component, endows the bioink with shear-thinning behavior. Moreover, the printed structure becomes robust under physiological conditions owing to the in situ chemical crosslinking catalyzed by mTG enzyme. Lattice, bowl, meniscus, and ear structures are printed to demonstrate the printing feasibility of such a composite bioink. Furthermore, the 3D-printed cell-laden constructs are proved to be a conducive biochemical environment that supports growth and proliferation of the encapsulated cells in vitro . In addition, the in vivo studies convince that the composite bioink possesses excellent biocompatibility and biodegradation. It is believed that the innovation of this new composite bioink will push forward the bioprinting technology onto a new stage.
(© 2021 IOP Publishing Ltd.)

The goal of this paper is to present a compact low-cost and low-power prototype of a pulsed Ultra Wide Band (UWB) oscillator and an UWB elliptical dipole antenna integrated on the same Radio Frequency (RF) Printed Circuit Board (PCB) and its digital control board for Real Time Locating System (RTLS) applications. The design is compatible with IEEE 802.15.4 high rate pulse repetition UWB standard being able to work between 6 GHz and 8.5 GHz with 500 MHz bandwidth and with a pulse duration of 2 ns. The UWB system has been designed using the CST Microwave Studio transient Electro-Magnetic (EM) circuit co-simulation method. This method integrates the functional circuit simulation together with the full wave (EM) simulation of the PCB's 3D model allowing fast parameter tuning. The PCB has been manufactured and the entire system has been assembled and measured. Simulated and measured results are in excellent agreement with respect to the radiation performances as well as the power consumption. A compact, very low-power and low-cost system has been designed and validated.

Computer-Aided Design trends, Denture, Partial trends, Humans, Lasers, Workflow, Denture Design methods, Denture Design trends, and Denture, Partial, Removable trends

Objective: Analyzing and comparing the fit and accuracy of removable partial denture (RPDs) frameworks fabricated with CAD/CAM and rapid prototyping methods with conventional techniques.
Materials and Methods: The present systematic review was carried out according to PRISMA guidelines. The search was carried out on PubMed/MEDLINE, Cochrane collaboration, Science direct, and Scopus scientific engines using selected MeSH keywords. The articles fulfilling the predefined selection criteria based on the fit and accuracy of removable partial denture (RPD) frameworks constructed from digital workflow (CAD/CAM; rapid prototyping) and conventional techniques were included.
Results: Nine full-text articles comprising 6 in vitro and 3 in vivo studies were included in this review. The digital RPDs were fabricated in all articles by CAD/CAM selective laser sintering and selective laser melting techniques. The articles that have used CAD/CAM and rapid prototyping technique demonstrated better fit and accuracy as compared to the RPDs fabricated through conventional techniques. The least gaps between the framework and cast (41.677 ± 15.546  μ m) were found in RPDs constructed through digital CAD/CAM systems.
Conclusion: A better accuracy was achieved using CAD/CAM and rapid prototyping techniques. The RPD frameworks fabricated by CAD/CAM and rapid prototyping techniques had clinically acceptable fit, superior precision, and better accuracy than conventionally fabricated RPD frameworks.
(Copyright © 2021 Naseer Ahmed et al.)

Conducting polymers are the natural choice for soft electronics. However, the main challenge is to pattern conducting polymers using a simple and rapid method to manufacture advanced devices. Filtration of conducting particle dispersions using a patterned membrane is a promising method. Here, we show the rapid prototyping of various micropatterned organic electronic heterostructures of PEDOT:PSS by inducing the formation of microscopic hydrogels, which are then filtered through membranes containing printed hydrophobic wax micropatterns. The hydrogels are retained on the un-patterned, hydrophilic regions, forming micropatterns, achieving a resolution reaching 100 μm. We further solve the problem of forming stacked devices by transferring the acidified PEDOT:PSS micropattern using the adhesive tape transfer method to form vertical heterostructures with other micropatterned electronic colloids such as CNTs, which are patterned using a similar technique. We demonstrate a number of different heterostructure devices including micro supercapacitors and organic electrochemical transistors and also demonstrate the use of acidified PEDOT:PSS microstructures in cell cultures to enable bioelectronics.
(This journal is © The Royal Society of Chemistry.)

Diffusion of Innovation, Humans, Internship and Residency methods, Needs Assessment, Curriculum, Education, Medical, Graduate methods, Inventions, Problem-Based Learning methods, and Surgeons education

Problem: Health professions education does not routinely incorporate training in innovation or creative problem solving. Although some models of innovation education within graduate medical education exist, they often require participants' full-time commitment and removal from clinical training or rely upon participants' existing expertise. There is a need for curricula that teach innovation skills that will enable trainees to identify and solve unmet clinical challenges in everyday practice. To address this gap in surgical graduate education, the authors developed the Surgical Program in Innovation (SPIN).
Approach: SPIN, a 6-month workshop-based curriculum, was established in 2016 in the Beth Israel Deaconess Medical Center Department of Surgery to teach surgical trainees the basics of the innovation process, focusing on surgeon-driven problem identification, product design, prototype fabrication, and initial steps in the commercialization process. Participating surgical residents and graduate students attend monthly workshops taught by medical, engineering, and medical technology (MedTech) industry faculty. Participants collaborate in teams to develop a novel device, fabricate a protype, and pitch their product to a panel of judges.
Outcomes: From academic years 2015-2016 to 2017-2018, 49 trainees, including 41 surgical residents, participated in SPIN. Across this period, 13 teams identified an unmet need, ideated a solution, and designed and pitched a novel device. Ten teams fabricated prototypes. The 22 SPIN participants who responded to both pre- and postcourse surveys reported significant increases in confidence in generating problem statements, computer-aided design, fabrication of a prototype, and initial commercialization steps (product pitching and business planning).
Next Steps: Incorporating innovation education and design thinking into clinical training will prove essential in preparing future physicians to be lifelong problem finders and solvers. The authors plan to expand SPIN to additional clinical specialties, as well as to assess its impact in fostering future innovation and collaboration among program participants.
(Copyright © 2021 by the Association of American Medical Colleges.)

Bio-inspired Dielectric Resonator Antennas (DRAs) are engaging more and more attention from the scientific community due to their exceptional wideband characteristic, which is especially desirable for the implementation of 5G communications. Nonetheless, since these antennas exhibit peculiar geometries in their micro-features, high dimensional accuracy must be accomplished via the selection of the most suitable fabrication process. In this study, the challenges to the manufacturing process presented by the wideband Spiral shell Dielectric Resonator Antenna (SsDRA), based on the Gielis superformula, are addressed. Three prototypes, made of three different photopolymer resins, were manufactured by bottom-up micro-Stereolithography (SLA). This process allows to cope with SsDRA's fabrication criticalities, especially concerning the wavy features characterizing the thin spiral surface and the micro-features located in close proximity to the spiral origin. The assembly of the SsDRAs with a ground plane and feed probe was also accurately managed in order to guarantee reliable and repeatable measurements. The scattering parameter S 11 trends were then measured by means of a Vector Network Analyzer, while the realized gains and 3D radiation diagrams were measured in the anechoic chamber. The experimental results show that all SsDRAs display relevant wideband behavior of 2 GHz at -10 dB in the sub-6 GHz range.

Genetically encoded biosensors based on engineered fluorescent proteins (FPs) are essential tools for monitoring the dynamics of specific ions and molecules in biological systems. Arsenic ion in the +3 oxidation state (As 3+ ) is highly toxic to cells due to its ability to bind to protein thiol groups, leading to inhibition of protein function, disruption of protein-protein interactions, and eventually to cell death. A genetically encoded biosensor for the detection of As 3+ could potentially facilitate the investigation of such toxicity both in vitro and in vivo. Here, we designed and developed two prototype genetically encoded arsenic biosensors (GEARs), based on a bacterial As 3+ responsive transcriptional factor AfArsR from Acidithiobacillus ferrooxidans . We constructed FRET-based GEAR biosensors by insertion of AfArsR between FP acceptor/donor FRET pairs. We further designed and engineered single FP-based GEAR biosensors by insertion of AfArsR into GFP. These constructs represent prototypes for a new family of biosensors based on the ArsR transcriptional factor scaffold. Further improvements of the GEAR biosensor family could lead to variants with suitable performance for detection of As 3+ in various biological and environmental systems.

Equipment Design, Polyurethanes, and Robotics

In the field of soft robotics, pneumatic elements play an important role due to their sensitive and adaptive behavior. Nevertheless, the rapid prototyping of such actuators is still challenging since conventional 3D printers are not designed to fabricate airtight objects or to specify their bending behavior by combining materials of different stiffness. In order to address this challenge, a tool changing multi-material 3D printer has been constructed, which can be equipped with various print-heads fitted to the specific application. By alternately processing filaments with varying mechanical properties, a series of pneumatic elements was produced. The actuators were printed in thermoplastic polyurethane with shore hardness A70 for flexible parts and D65 for stiff parts. A novel procedure for the feature adaptation of the flow rate allowed the fabrication of vertically printed flexible membranes with a thickness of just 500 μ m. This way the bending and expanding printed structures can all be actuated with a pressure of 100 kPa or less. Furthermore, a new kind of generic actuator that is customizable to specific tasks and can perform complex motion behavior was designed. All together, these actuators demonstrate the high potential of the developed platform for further research on and production of soft robotic elements and complex pressurized systems.
(Creative Commons Attribution license.)

In the era of modern medicine, the number of invasive treatments increases. Artificial devices used in medicine are associated with an increased risk of secondary infections. Bacterial biofilm development observed on the implanted surface is challenging to treat, primarily due to low antibiotics penetration. In our study, the preparation of a new polycarbonate composite, filled with nanosilver, nanosilica and rhodamine B derivative, suitable for three-dimensional printing, is described. Polymer materials with antimicrobial properties are known. However, in most cases, protection is limited to the outer layers only. The newly developed materials are protected in their entire volume. Moreover, the antibacterial properties are retained after multiple high-temperature processing were performed, allowing them to be used in 3D printing. Bacterial population reduction was observed, which gives an assumption for those materials to be clinically tested in the production of various medical devices and for the reduction of morbidity and mortality caused by multidrug-resistant bacteria.

Introduction: Collaborating with end-users to develop interventions tailored to fit unique circumstances is proposed as a way to improve relevance and effectiveness of an intervention. This study used a local needs driven approach to develop a health literacy intervention for caregivers in Ghana concerning management of malaria in children under 5 years.
Method: For the period, November 2017-February 2019, we carried out the study using a three-phase framework including: 1) Needs assessment based on data from questionnaires, focus groups, individual interviews and observations, 2) Co-creation of a board game and brochures for health education at Child Welfare Clinics to address needs in health literacy concerning malaria and 3) Development of a prototype of the game, brochures as well as determining feasibility. In addition to the research team, health administrators, community health workers, designers and caregivers contributed to the development of the intervention.
Findings: The needs assessment contributed to the development of interactive and useful materials including a board game and brochures, to help bridge the gaps in health literacy among caregivers. Co-creation of the materials and prototyping yielded a varying sense of ownership among stakeholders. End-users' engagement and participation in developing the intervention resulted in a high interest and adherence to interventions. However, high attrition rates of health workers and caregivers' inconsistent use of the Child Welfare Clinics challenged sustainability of this intervention.
Conclusion: Co-creation led to an interactive intervention. The interactive nature of the board game and brochures resulted in a better caregiver-health provider relationship and a sense of recognition of a more participatory approach to health delivery. We recommend co-creation as an approach to develop needs-driven interventions in a context like Ghana. Still, a stronger buy-in at the top-level of health management would improve sustainability and reach a larger audience.
(© 2021. The Author(s).)

Bacteria metabolism, Biotechnology methods, Escherichia coli genetics, Escherichia coli metabolism, Gene Expression Regulation, Plasmids genetics, Plasmids metabolism, Bacteria genetics, Biological Products metabolism, Industrial Microbiology methods, Metabolic Engineering methods, Metabolic Networks and Pathways genetics, and Synthetic Biology methods

Metabolic engineering technologies have been employed with increasing success over the last three decades for the engineering and optimization of industrial host strains to competitively produce high-value chemical targets. To this end, continued reductions in the time taken from concept, to development, to scale-up are essential. Design-Build-Test-Learn pipelines that are able to rapidly deliver diverse chemical targets through iterative optimization of microbial production strains have been established. Biofoundries are employing in silico tools for the design of genetic parts, alongside combinatorial design of experiments approaches to optimize selection from within the potential design space of biological circuits based on multi-criteria objectives. These genetic constructs can then be built and tested through automated laboratory workflows, with performance data analysed in the learn phase to inform further design. Successful examples of rapid prototyping processes for microbially produced compounds reveal the potential role of biofoundries in leading the sustainable production of next-generation bio-based chemicals.
(© 2021 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

Biofuels, Cell-Free System, High-Throughput Screening Assays methods, Microorganisms, Genetically-Modified, Mutation, Real-Time Polymerase Chain Reaction methods, Reverse Transcriptase Polymerase Chain Reaction methods, CRISPR-Cas Systems, Cyanobacteria genetics, Gene Editing methods, Metabolic Engineering methods, Promoter Regions, Genetic, and Transcription, Genetic genetics

Cyanobacteria are promising microbial hosts for the production of diverse biofuels and biochemicals. However, compared to other model microbial hosts such as Escherichia coli and yeast, it takes a long time to genetically modify cyanobacteria. One way to efficiently engineer cyanobacteria while minimizing genetic engineering would be to develop a fast, high-throughput prototyping tool for cyanobacteria. In this study, we developed a CRISPR/Cas12a-based assay coupled with cyanobacteria cell-free systems to rapidly prototype promoter characteristics. Using this newly developed assay, we demonstrated cyanobacteria cell-free transcription for the first time and confirmed a positive correlation between the in vitro and in vivo transcription performance. Furthermore, we generated a synthetic promoter library and evaluated the characteristics of promoter subregions by using the assay. Varied promoter strength derived from random mutations were rapidly and effectively measured in a high-throughput way. We believe that this study offers an easily applicable and rapid prototyping platform to characterize promoters for cyanobacterial engineering.

Fermentation, Methyltransferases metabolism, Time Factors, Escherichia coli metabolism, Fluorescence Resonance Energy Transfer, and Methyltransferases genetics

O-Methyltransferases are ubiquitous enzymes involved in biosynthetic pathways for secondary metabolites such as bacterial antibiotics, human catecholamine neurotransmitters, and plant phenylpropanoids. While thousands of putative O-methyltransferases are found in sequence databases, few examples are functionally characterized. From a pathway engineering perspective, however, it is crucial to know the substrate and product ranges of the respective enzymes to fully exploit their catalytic power. In this study, we developed an in vitro prototyping workflow that allowed us to screen ∼30 enzymes against five substrates in 3 days with high reproducibility. We combined in vitro transcription/translation of the genes of interest with a microliter-scale enzymatic assay in 96-well plates. The substrate conversion was indirectly measured by quantifying the consumption of the S-adenosyl-L-methionine co-factor by time-resolved fluorescence resonance energy transfer rather than time-consuming product analysis by chromatography. This workflow allowed us to rapidly prototype thus far uncharacterized O-methyltransferases for future use as biocatalysts.
(Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: The COVID-19 pandemic showed an urgent need for decision support systems to help doctors at a time of stress and uncertainty. However, significant differences in hospital conditions, as well as skepticism of doctors about machine learning algorithms, limit their introduction into clinical practice. Our goal was to test and apply the principle of "patient-like-mine" decision support in rapidly changing conditions of a pandemic.
Methods: In the developed system we implemented a fuzzy search that allows a doctor to compare their medical case with similar cases recorded in their medical center since the beginning of the pandemic. Various distance metrics were tried for obtaining clinically relevant search results. With the use of R programming language, we designed the first version of the system in approximately a week. A set of features for the comparison of the cases was selected with the use of random forest algorithm implemented in Caret. Shiny package was chosen for the design of GUI.
Results: The deployed tool allowed doctors to quickly estimate the current conditions of their patients by means of studying the most similar previous cases stored in the local health information system. The extensive testing of the system during the first wave of COVID-19 showed that this approach helps not only to draw a conclusion about the optimal treatment tactics and to train medical staff in real-time but also to optimize patients' individual testing plans.
Conclusions: This project points to the possibility of rapid prototyping and effective usage of "patient-like-mine" search systems at the time of a pandemic caused by a poorly known pathogen.
(© The Author(s) 2021.)

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

Many 10-14 year olds are at the early stages of using social media, habits they develop on popular platforms can have lasting effects on their socio-emotional wellbeing. We led a remote innovation workshop with 23 middle schoolers on digital wellbeing, identity exploration, and computational concepts related to social computing. This workshop was a unique opportunity to reflect on emergent habits, discuss them with peers, and imagine oneself as an ICT innovator. Resulting themes related to participants' social wellbeing online included a) sense of belonging to communities of interest, friends, and family, b) self-care and social support strategies involving managing risks, control, and empathy, and c) experimentation while building self-confidence and bravely exploring audience reactions. Participants iteratively designed and tested a sandbox social network website, resulting in Social Sketch. Reflecting on our study, we describe the process for conceptualizing Social Sketch, and challenges in social media innovation with teenagers.

Adjuvants, Immunologic, Animals, Antibodies, Bacterial, Extracellular Vesicles immunology, Extracellular Vesicles microbiology, Gram-Negative Bacteria, Humans, Immunity, Humoral, Mice, Mice, Inbred BALB C, Vaccination, Bacterial Outer Membrane Proteins immunology, Bacterial Vaccines, Drug Resistance, Multiple, Bacterial, and Gram-Negative Bacterial Infections prevention control

Hospital-acquired infections due to multi-drug resistant Gram-negative organisms (MDRGNO) pose a major threat to global health. A vaccine preventing colonization and consecutive infection with MDRGNO could be particularly valuable, as therapeutic options become increasingly limited. Outer membrane vesicles (OMV) of Escherichia coli strain CFT073 as well as three MDRGNO strains that had caused severe infections in humans were administered intranasally to mice, with and without cholera toxin as an adjuvant. The humoral immune responses were comparatively matched with the sera of patients, who had suffered an infection caused by the respective bacterium. Additionally, systemic and local toxicity was evaluated. Intranasal vaccination with OMV could elicit solid humoral immune responses (total IgM and IgG), specific for the respective MDRGNO in mice; decoration of vital bacterial membranes with antibodies was comparable to patients who had survived systemic infection with the respective bacterial isolate. After intranasal vaccination of mice with OMV no signs of local or systemic toxicity were observed. Intranasal vaccination with OMV may open up a rapid vaccine approach to prevent colonization and/or infection with pathogenic MDRGNOs, especially in an outbreak setting within a hospital. It may also be an option for patients who have to undergo elective interventions in centers with a high risk of infection for certain common MDRGNO. Future studies need to include challenge experiments as well as phase I trials in humans.
(© 2021 The Authors. Microbiology and Immunology published by The Societies and John Wiley & Sons Australia, Ltd.)

In this paper, we propose a novel design and optimization environment for inertial MEMS devices based on a computationally efficient schematization of the structure at the a device level. This allows us to obtain a flexible and efficient design optimization tool, particularly useful for rapid device prototyping. The presented design environment- feMEMSlite -handles the parametric generation of the structure geometry, the simulation of its dynamic behavior, and a gradient-based layout optimization. The methodology addresses the design of general inertial MEMS devices employing suspended proof masses, in which the focus is typically on the dynamics associated with the first vibration modes. In particular, the proposed design tool is tested on a triaxial beating-heart MEMS gyroscope, an industrially relevant and adequately complex example. The sensor layout is schematized by treating the proof masses as rigid bodies, discretizing flexural springs by Timoshenko beam finite elements, and accounting for electrostatic softening effects by additional negative spring constants. The MEMS device is then optimized according to two possible formulations of the optimization problem, including typical design requirements from the MEMS industry, with particular focus on the tuning of the structural eigenfrequencies and on the maximization of the response to external angular rates. The validity of the proposed approach is then assessed through a comparison with full FEM schematizations: rapidly prototyped layouts at the device level show a good performance when simulated with more complex models and therefore require only minor adjustments to accomplish the subsequent physical-level design.

Caco-2 Cells, Cell Culture Techniques, Humans, Organoids, Lab-On-A-Chip Devices, and Microfluidics

Microfluidic organs-on-chips aim to realize more biorelevant in vitro experiments compared to traditional two-dimensional (2D) static cell culture. Often such devices are fabricated via poly(dimethylsiloxane) (PDMS) soft lithography, which offers benefits (e.g., high feature resolution) along with drawbacks (e.g., prototyping time/costs). Here, we report benchtop fabrication of multilayer, PDMS-free, thermoplastic organs-on-chips via laser cut and assembly with double-sided adhesives that overcome some limitations of traditional PDMS lithography. Cut and assembled chips are economical to prototype ($2 per chip), can be fabricated in parallel within hours, and are Luer compatible. Biocompatibility was demonstrated with epithelial line Caco-2 cells and primary human small intestinal organoids. Comparable to control static Transwell cultures, Caco-2 and organoids cultured on chips formed confluent monolayers expressing tight junctions with low permeability. Caco-2 cells-on-chip differentiated ∼4 times faster, including increased mucus, compared to controls. To demonstrate the robustness of cut and assemble, we fabricated a dual membrane, trilayer chip integrating 2D and 3D compartments with accessible apical and basolateral flow chambers. As proof of concept, we cocultured a human, differentiated monolayer and intact 3D organoids within multilayered contacting compartments. The epithelium exhibited 3D tissue structure and organoids expanded close to the adjacent monolayer, retaining proliferative stem cells over 10 days. Taken together, cut and assemble offers the capability to rapidly and economically manufacture microfluidic devices, thereby presenting a compelling fabrication technique for developing organs-on-chips of various geometries to study multicellular tissues.

Powders and Technology, Pharmaceutical

Continuous manufacturing is an important element of future manufacturing solutions enabling for both high product quality and streamlined development process. The increasing possibilities with computer simulations allow for innovating novel mixing principles applicable for continuous manufacturing. However, these innovative ideas based on simulations need experimental validation. The use of rapid prototyping based on additive manufacturing opens a possibility to evaluate these ideas at a low cost. In this study, a novel powder mixing geometry was prototyped using additive manufacturing and further, interfaced with an in-line near-IR spectrometer allowing for investigating the residence time distribution (RTD) in this geometry.
(Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Humans, Middle Aged, Osteotomy, Printing, Three-Dimensional, Radius, Range of Motion, Articular, Treatment Outcome, Fractures, Malunited diagnostic imaging, Fractures, Malunited surgery, Radius Fractures diagnostic imaging, and Radius Fractures surgery

Introduction: Distal radius fractures (DRF) are among the most frequent in the body. About one third of these fractures can result in malunion with restriction of movement and pain in the wrist, the treatment in these cases consists of corrective osteotomy of the deformity. Due to its three-dimensional (3D) complexity, careful preoperative planning is a fundamental step in correction. The prototyping from the 3D reconstruction of the computed tomography of the affected wrist, allows the real understanding of the deformity.
Methods: Patients with malunion of the distal radius with indication for surgical treatment, from December 2019, were included in the group of corrective osteotomies through planning with prototyping in 3D printing. The postoperative functional outcome was assessed by the Disabilities of the Arm, Shoulder and Hand Score (DASH) and visual analogue scale (VAS). Radiographic data including radial inclination, volar tilt and joint step were recorded from standard posteroanterior and lateral radiographic views.
Results: A total of 9 patients were included. The mean age was 47 years. The average postoperative DASH value of the patients was 24.9 and VAS was 3.6. Radiographically, the palmar tilt had an average improvement of 25.22°, and the radial inclination had an average improvement of 2°.
Conclusion: Corrective osteotomy through planning with prototyping in 3D printing is an effective method of treating symptomatic distal radius malunions. The possibility of performing the osteotomy in a 3D model, simulating the surgery, making the procedure more predictable.
(Copyright © 2021. Published by Elsevier Ltd.)

Animals, Biocompatible Materials chemistry, Cell Line, Disease Models, Animal, Electrocardiography, Electrophysiological Phenomena, Image Processing, Computer-Assisted, Ink, Male, Mice, Mice, Inbred C57BL, Molecular Dynamics Simulation, Myoblasts metabolism, Myoblasts pathology, Prostheses and Implants, Silicones chemistry, Spatio-Temporal Analysis, Swine, Ultrasonography, Biosensing Techniques instrumentation, Biosensing Techniques methods, Diagnostic Imaging methods, Myocardial Infarction diagnostic imaging, and Pericardium diagnostic imaging

The growing need for the implementation of stretchable biosensors in the body has driven rapid prototyping schemes through the direct ink writing of multidimensional functional architectures. Recent approaches employ biocompatible inks that are dispensable through an automated nozzle injection system. However, their application in medical practices remains challenged in reliable recording due to their viscoelastic nature that yields mechanical and electrical hysteresis under periodic large strains. Herein, we report sponge-like poroelastic silicone composites adaptable for high-precision direct writing of custom-designed stretchable biosensors, which are soft and insensitive to strains. Their unique structural properties yield a robust coupling to living tissues, enabling high-fidelity recording of spatiotemporal electrophysiological activity and real-time ultrasound imaging for visual feedback. In vivo evaluations of custom-fit biosensors in a murine acute myocardial infarction model demonstrate a potential clinical utility in the simultaneous intraoperative recording and imaging on the epicardium, which may guide definitive surgical treatments.

Cell-Free System, Polymerase Chain Reaction, DNA, and Nucleic Acid Amplification Techniques

This protocol describes the design of a minimal DNA template and the steps for enzymatic amplification, enabling rapid prototyping of assayable proteins in less than 24 h using cell-free expression. After receiving DNA from a vendor, the gene fragment is PCR-amplified, cut, circularized, and cryo-banked. A small amount of the banked DNA is then diluted and amplified significantly (up to 10 6 x) using isothermal rolling circle amplification (RCA). RCA can yield microgram quantities of the minimal expression template from picogram levels of starting material (mg levels if all starting synthetic fragment is used). In this work, a starting amount of 20 pg resulted in 4 µg of the final product. The resulting RCA product (concatemer of the minimal template) can be added directly to a cell-free reaction with no purification steps. Due to this method being entirely PCR-based, it may enable future high-throughput screening efforts when coupled with automated liquid handling systems.

Conversion of terahertz radiation into thermal radiation is a promising approach for the development of low cost terahertz instruments. Here, we experimentally demonstrate bispectral terahertz-to-infrared conversion using metamaterials fabricated using a rapid prototyping technique. The converter unit cell is composed of two metal-insulator-metal (MIM) antennas absorbing independently the terahertz radiation at 96 and 130 GHz and a thin carbon nanotubes (CNT) layer used as a thermal emitter. The converter unit cell has a typical λ/100 thickness and sub-wavelength lateral dimensions. The terahertz absorption of the converter was observed by monitoring its thermal emission using an infrared camera. Within the first hundred milliseconds of the terahertz pulse, thermal radiation from the CNTs only increases at the location of the MIM antennas, thus allowing to record the terahertz response of each MIM antenna independently. Beyond 100 ms, thermal diffusion causes significant cross-talk between the pixels, so the spectral information is more difficult to extract. In a steady state regime, the minimum terahertz power that can be detected is 5.8 µW at 130 GHz. We conclude that the converter provides a suitable low-cost solution for fast multi-spectral terahertz imaging with resolution near the diffraction limit, using an infrared camera in combination with a tunable source.

Culture Media, Desiccation, Electrochemical Techniques instrumentation, Shewanella metabolism, Bioelectric Energy Sources, Electrochemical Techniques methods, Electrodes, Equipment Design, and Shewanella isolation purification

In this study, the electrospinning technique is shown to be a viable method for the synthesis of a bacteria-encapsulating bioanode. A coaxial setup was designed to yield in one step a bioanode made of two fibers networks: one encapsulating the electroactive bacteria Shewanella oneidensis and the other one providing the necessary conductivity for electron transport throughout the bioelectrode. The electrical conductivity of this "integrated bioanode" (∼10-2 to 10-3 S cm-1) was deemed satisfactory and it was then included into a microbial fuel cells (MFC). The resulting MFC exhibited electricity generation. We further demonstrate that this electrode can be cryodesiccated and still exhibits an electrochemical activity once integrated into the MFC reactor. Its volume current and power densities were similar to those recorded for the fresh electrospun bioanode (up to 3260 A m-3 and 230 W m-3 for the thin cryodesiccated bioanode (∼410 μm)). Such impressive volume current densities for thin electrospun systems may be for instance envisioned to be applied to wearable or paper-based MFCs which require a certain flexibility.

Distal radial fractures are very common. Vicious consolidation can occur in up to one third of these fractures, resulting in wrist pain, restricted movement, and, eventually, physical limitation or disability. The treatment of this condition consists in corrective osteotomy, which requires careful preoperative planning due to its three-dimensional complexity, especially in injuries with joint involvement. Recently, prototyping based on three-dimensional (3D) reconstruction of computed tomography (CT) scans has been used for osteotomy planning in a 3D anatomical model. It allows a better understanding of the deformity in a realistic surgical approach, leading to safer, faster, and more predictable procedures. The aim of the present study is to present this technique and show its use in two clinical cases.
(Sociedade Brasileira de Ortopedia e Traumatologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Three-dimensional printed custom cutting guides (CCGs) are becoming more and more investigated in medical literature, as a patient-specific approach is often desired and very much needed in today's surgical practice. Three-dimensional printing applications and computer-aided surgical simulations (CASS) allow for meticulous preoperatory planning and substantial reductions of operating time and risk of human error. However, several limitations seem to slow the large-scale adoption of 3D printed CCGs. CAD designing and 3D printing skills are inevitably needed to develop workflow and address the study; therefore, hospitals are pushed to include third-party collaboration, from highly specialized medical centers to industrial engineering companies, thus increasing the time and cost of labor. The aim of this study was to move towards the feasibility of an in-house, low-cost CCG 3D printing methodology for pediatric orthopedic (PO) surgery. The prototype of a femoral cutting guide was developed for its application at the IOR-Rizzoli Orthopedic Institute of Bologna. The element was printed with an entry-level 3D printer with a high-temperature PLA fiber, whose thermomechanical properties can withstand common steam heat sterilization without bending or losing the original geometry. This methodology allowed for extensive preoperatory planning that would likewise reduce the overall surgery time, whilst reducing the risks related to the intervention.

The main objective of the study was to design a pneumatic directional control valve for controlling pneumatic drives and produce it using a rapid prototyping technique. As the basic design assumption was to achieve high performance through a high flow rate and a low pressure drop, it was necessary to determine two flow parameters: the sonic conductance and the critical pressure ratio. The flow rate of compressed air and the diameters of the pneumatic conduits and fittings are important as they affect the rate of travel of the pneumatic cylinder piston. The 3D solid model of the directional control valve, developed in a CAD program, was used to simulate and optimize the flow rate. The analysis was performed by means of ANSYS CFX, a computational flow dynamics program. The main elements of the valve, i.e., the spool and the body, were produced using the PolyJet Matrix technology. The prototype was tested experimentally to determine the nominal flow-rate, calculate the flow parameters in accordance with the ISO 6358-1989 standard and compare them with the CFD simulation data. The simulation results showed very good agreement with the measurement data. The CFD analysis of the 3D solid model enabled us to optimize the flow of compressed air through the valve. The rapid prototyping method was found to be suitable to produce a fully functional directional control valve, which was confirmed through measurements at a test stand. The attempt to combine rapid prototyping used to fabricate pneumatic directional control valves with CFD used to simulate their operation was successful. The study shows that it is possible to design and construct a fully functional directional control valve characterized by high efficiency, high performance and a small pressure loss in a very short time and at a very low cost, which makes rapid prototyping superior to conventional methods of prototype making.

Replacing synthetic pesticides and antimicrobials with plant-based extracts is a current alternative adopted by traditional and family farmers and many organic farming pioneers. A range of natural extracts are already being marketed for agricultural use, but many other plants are prepared and used empirically. A further range of plant species that could be effective in protecting different crops against pests and diseases in Africa could be culled from the large volume of knowledge available in the scientific literature. To meet this challenge, data on plant uses have been compiled in a knowledge base and a software prototype was developed to navigate this trove of information. The present paper introduces this so-called Knomana Knowledge-Based System, while providing outputs related to Spodoptera frugiperda and Tuta absoluta, two invasive insect species in Africa. In early October 2020, the knowledge base hosted data obtained from 342 documents. From these articles, 11,816 uses-experimental or applied by farmers-were identified in the plant health field. In total, 384 crop pest species are currently reported in the knowledge base, in addition to 1547 botanical species used for crop protection. Future prospects for applying this interdisciplinary output to applications under the One Health approach are presented.

Terahertz technology has greatly benefited from the recent development and generalization of prototyping technologies such as 3D printing and laser machining. These techniques can be used to rapidly fabricate optical devices for applications in sensing, imaging and communications. In this paper, we introduce hot stamping, a simple inexpensive and rapid technique to form 2D metallic patterns that are suitable for many terahertz devices. We fabricate several example devices to illustrate the versatility of the technique, including metasurfaces made of arrays of split-ring resonators with resonances up to 550 GHz. We also fabricate a wire-grid polarizer for use as a polarizing beam splitter. The simplicity and low cost of this technique can help in rapid prototyping and realization of future terahertz devices.

The study of cellular migration dynamics and strategies plays a relevant role in the understanding of both physiological and pathological processes. An important example could be the link between cancer cell motility and tumor evolution into metastatic stage. These strategies can be strongly influenced by the extracellular environment and the consequent mechanical constrains. In this framework, the possibility to study the behavior of single cells when subject to specific topological constraints could be an important tool in the hands of biologists. Two-photon polymerization is a sub-micrometric additive manufacturing technique that allows the fabrication of 3D structures in biocompatible resins, enabling the realization of ad hoc biochips for cell motility analyses, providing different types of mechanical stimuli. In our work, we present a new strategy for the realization of multilayer microfluidic lab-on-a-chip constructs for the study of cell motility which guarantees complete optical accessibility and the possibility to freely shape the migration area, to tailor it to the requirements of the specific cell type or experiment. The device includes a series of micro-constrictions that induce different types of mechanical stress on the cells during their migration. We show the realization of different possible geometries, in order to prove the versatility of the technique. As a proof of concept, we present the use of one of these devices for the study of the motility of murine neuronal cancer cells under high physical confinement, highlighting their peculiar migration mechanisms.
(Copyright © 2021 Sala, Ficorella, Martínez Vázquez, Eichholz, Käs and Osellame.)

Algorithms, Information Storage and Retrieval, Sequence Analysis, Computational Biology, and Software

Motivation: Many software libraries for using Hidden Markov Models in bioinformatics focus on inference tasks, such as likelihood calculation, parameter-fitting and alignment. However, construction of the state machines can be a laborious task, automation of which would be time-saving and less error-prone.
Results: We present Machine Boss, a software tool implementing not just inference and parameter-fitting algorithms, but also a set of operations for manipulating and combining automata. The aim is to make prototyping of bioinformatics HMMs as quick and easy as the construction of regular expressions, with one-line 'recipes' for many common applications. We report data from several illustrative examples involving protein-to-DNA alignment, DNA data storage and nanopore sequence analysis.
Availability and Implementation: Machine Boss is released under the BSD-3 open source license and is available from http://machineboss.org/.
Supplementary Information: Supplementary data are available at Bioinformatics online.
(© The Author(s) 2020. Published by Oxford University Press.)

Dimethylpolysiloxanes chemistry and Microtechnology

A major goal of polydimethylsiloxane (PDMS) microfabrication is to develop a simple and inexpensive method for rapid fabrication. Despite the recent advancements in this field, facile PDMS microfabrication on non-planar surfaces remains elusive. Here we report a facile method for rapid prototyping of PDMS microdevices via µ PLAT (microscale plasma-activated templating) on non-planar surfaces through micropatterning of hydrophilic/hydrophobic (HL/HB) interface by flexible polyvinyl chloride (PVC) hollow-out mask. This mask can be easily prepared with flexible PVC film through a cutting crafter and applied as pattern definer during the plasma treatment for microscale HL/HB interface formation on different substrates. The whole process requires low inputs in terms of time as well as toxic chemicals. Inspired by liquid molding, we demonstrated its use for rapid prototyping of PDMS microstructures. Following the proof-of-concept study, we also demonstrated the use of the flexible hollow-out mask to facilitate cell patterning on curved substrates, which is difficult to realize with conventional methods. Collectively, our work utilizes flexible and foldable PVC film as mask materials for facile microscale HL non-planar surface modification to establish a useful tool for PDMS prototyping and cell patterning.
(© 2021 IOP Publishing Ltd.)

Computer-Aided Design, Dental Prosthesis Design, Dental Prosthesis, Implant-Supported, Humans, Workflow, Dental Implants, and Mouth, Edentulous

This report presents a completely digital workflow utilizing digital intraoral scanning, rapid prototyping techniques, and a monolithic final restoration. A complete fixed prosthesis supported by six implants was used to replace a patient's periodontally compromised mandibular natural dentition. A staged approach was used in which a series of milled and 3D-printed provisional restorations were fabricated to help the patient transition to the dental implant rehabilitation. This cast-free approach allowed for increased patient comfort and greater time efficiency in clinical steps, as each provisional was digitally preplanned and readily available to the clinician before each step.

Nanoparticle (NP) concentration is crucial for liquid biopsies and analysis, and various NP concentrators (NPCs) have been developed. Methods using ion concentration polarization (ICP), an electrochemical phenomenon based on NPCs consisting of microchannels, have attracted attention because samples can be non-invasively concentrated using devices with simple structures. The fabrication of such NPCs is limited by the need for lithography, requiring special equipment and time. To overcome this, we reported a rapid prototyping method for NPCs by extending the previously developed hydrogel molding method, a microchannel fabrication method using hydrogel as a mold. With this, we fabricated NPCs with both straight and branched channels, typical NPC configurations. The generation of ICP was verified, and an NP concentration test was performed using dispersions of negatively and positively charged NPs. In the straight-channel NPC, negatively and positively charged NPs were concentrated >50-fold and >25-fold the original concentration, respectively. To our knowledge, this is the first report of NP concentration via ICP in a straight-channel NPC. Using a branched-channel NPC, maximum concentration rates of 2.0-fold and 1.7-fold were obtained with negatively and positively charged NPs, respectively, similar to those obtained with NPCs fabricated through conventional lithography. This rapid prototyping method is expected to promote the development of NPCs for liquid biopsy and analysis.

Back pain resulted from spine disorders reaches 60-80% prevalence in humans, which seriously influences life quality and retards economic production. Conventional electrical pain relief therapy uses radiofrequency to generate a high temperature of 70-85 °C on the electrode tip to destroy the neural transmission and stop the pain. However, due to the larger area of stimulation, eliciting significant side effects, such as paralysis, contraction, and a slightly uncomfortable feeling, our study aimed to design a tiny and stretchable neural stimulatory electrode that could be precisely anchored adjacent to the dorsal root ganglion which needs therapy and properly interfere with the sensory neural transmission. We also designed a subcutaneously implantable wireless power transmission (WPT) device to drive the neural stimulatory electrode. Through the study, we elaborated the design concept and clinical problems, and achieved: (1) the architecture design and simulation of the transdermal wireless power transferred device, (2) a wrap-able pulsed radiofrequency (PRF) stimulatory electrode, (3) an insulation packaging design of the titanium protection box. The feasibility study and hands-on prototype were also carried out.

Additive manufacturing is a promising tool for the rapid prototyping of terahertz metamaterials at low-cost. In this letter, a terahertz metamaterial is fabricated using a microplotter system on a flexible polyimide film. The limits of the rapid prototyping technique is investigated both experimentally and numerically in order to determine the spectral range accessible by the fabricated metamaterials. Here, the metamaterial is composed of four arrays of metal-insulator-metal (MIM) antennas exhibiting a Fabry Perot resonance at frequencies from 0.25 to 0.8 THz. From a structural analysis of the printed antennas, we determined that the printing resolution is limited to about 5 μm. The arrays are analyzed by terahertz time-domain spectroscopy (THz-TDS). The good agreement between THz-TDS measurements and numerical simulations showed that the microplotter system can be used for rapid prototyping by adjusting a limited number of fabrication parameters.

Algorithms, Data Analysis, Genomics, Language, Programming Languages, Reproducibility of Results, Ribosomes physiology, Software, Computational Biology education, Computing Methodologies, User-Computer Interface, and Workflow

Workflow management systems represent, manage, and execute multistep computational analyses and offer many benefits to bioinformaticians. They provide a common language for describing analysis workflows, contributing to reproducibility and to building libraries of reusable components. They can support both incremental build and re-entrancy-the ability to selectively re-execute parts of a workflow in the presence of additional inputs or changes in configuration and to resume execution from where a workflow previously stopped. Many workflow management systems enhance portability by supporting the use of containers, high-performance computing (HPC) systems, and clouds. Most importantly, workflow management systems allow bioinformaticians to delegate how their workflows are run to the workflow management system and its developers. This frees the bioinformaticians to focus on what these workflows should do, on their data analyses, and on their science. RiboViz is a package to extract biological insight from ribosome profiling data to help advance understanding of protein synthesis. At the heart of RiboViz is an analysis workflow, implemented in a Python script. To conform to best practices for scientific computing which recommend the use of build tools to automate workflows and to reuse code instead of rewriting it, the authors reimplemented this workflow within a workflow management system. To select a workflow management system, a rapid survey of available systems was undertaken, and candidates were shortlisted: Snakemake, cwltool, Toil, and Nextflow. Each candidate was evaluated by quickly prototyping a subset of the RiboViz workflow, and Nextflow was chosen. The selection process took 10 person-days, a small cost for the assurance that Nextflow satisfied the authors' requirements. The use of prototyping can offer a low-cost way of making a more informed selection of software to use within projects, rather than relying solely upon reviews and recommendations by others.

Reproducibility of Results, Molecular Dynamics Simulation, and Software

Ensembler is a Python package that enables method prototyping using 1D and 2D model systems and allows deepening of the understanding of different molecular dynamics (MD) methods, starting from basic techniques to enhanced sampling and free-energy approaches. The ease of installing and using the package increases shareability, comparability, and reproducibility of scientific code developments. Here, we describe the implementation and usage of the package and provide an application example for free-energy calculation. The code of Ensembler is freely available on GitHub at https://github.com/rinikerlab/Ensembler.

Aircraft, Humans, Privacy, and Virtual Reality

Background: The Human-Centered Design methodology advocates VR prototyping, as an effective tool to evaluate concepts in a cost-efficient, time-saving way. It is the question of whether it works in the development of a product intended to increase privacy while flying.
Objective: The current study aims at the application of virtual reality on the evaluation of a new privacy bubble called PRIVA for the passenger cabin.
Methods: An interactive VR was created and aligned with the HTC VIVE headset. 40 participants took part in the experiment as well as in the post-experiment survey.
Results: The concept was in overall, desirable as it was perceived to be more private, comfortable, satisfactory, effective, and appealing to participants compared to the current seat experiences. It was also perceived as more satisfactory with regards to the activities.
Conclusions: The VR was effective, although there are limitations, the product seems promising and should be developed further.

Clostridium, Protein Biosynthesis, Cell-Free System metabolism, Metabolic Engineering, and Metabolic Networks and Pathways

Gas fermentation by autotrophic bacteria, such as clostridia, offers a sustainable path to numerous bioproducts from a range of local, highly abundant, waste and low-cost feedstocks, such as industrial flue gases or syngas generated from biomass or municipal waste. Unfortunately, designing and engineering clostridia remains laborious and slow. The ability to prototype individual genetic part function, gene expression patterns, and biosynthetic pathway performance in vitro before implementing designs in cells could help address these bottlenecks by speeding up design. Unfortunately, a high-yielding cell-free gene expression (CFE) system from clostridia has yet to be developed. Here, we report the development and optimization of a high-yielding (236 ± 24 μg/mL) batch CFE platform from the industrially relevant anaerobe, Clostridium autoethanogenum. A key feature of the platform is that both circular and linear DNA templates can be applied directly to the CFE reaction to program protein synthesis. We demonstrate the ability to prototype gene expression, and quantitatively map aerobic cell-free metabolism in lysates from this system. We anticipate that the C. autoethanogenum CFE platform will not only expand the protein synthesis toolkit for synthetic biology, but also serve as a platform in expediting the screening and prototyping of gene regulatory elements in non-model, industrially relevant microbes.
(Copyright © 2020 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.)

Equipment Design instrumentation, Female, Health Personnel statistics numerical data, Humans, Male, Masks economics, COVID-19 prevention control, Equipment Design methods, Masks standards, and Printing, Three-Dimensional economics

Background: COVID-19 is a global pandemic. The virus spreads through respiratory droplets and close contact. Therefore, the availability of personal protective equipment (PPE) for healthcare professionals is essential. 3D printing technology could represent a valid option to ameliorate PPE shortages.
Methodology: Custom-made face mask were designed on the basis of facial scan and then 3D-printed. The whole protocol is executed with freeware software and only required a 3D printer. Six healthcare workers wore the device weekly thus expressing a judgment regarding quality of work, respiratory and skin comfort.
Results: The estimated total cost of a single mask is approximately 5 USD. The virtual design of a complete mask lasted 68 minutes on average. Most healthcare workers rated comfort as very good.
Conclusions: Based on the encouraging results obtained, we can confidently confirm that custom-made masks are novel and useful devices that may be used in the fight against COVID-19.
(Copyright (c) 2021 Pasquale Piombino, Umberto Committeri, Giovanna Norino, Luigi Angelo Vaira, Stefania Troise, Fabio Maglitto, Domenico Mariniello, Giacomo De Riu, Luigi Califano.)

Adolescent, Child, Child, Preschool, Emergencies, Female, Humans, Infant, Male, Medical Oncology, Qualitative Research, Surveys and Questionnaires, Telemedicine, Young Adult, Caregivers, and Neoplasms therapy

As part of a larger project to co-design and create a mHealth tool to support caregivers of children with cancer, we performed a pilot, qualitative study. For this portion of the project, we engaged with caregivers of children with cancer to co-create and refine a low-fidelity prototype of the Children's Oncology Planning for Emergencies mHealth tool. Testing was accomplished through recorded semi-structured interviews with each caregiver as they interacted with a low-fidelity wireframe using Adobe Xd. Through the engagement of our key stakeholders, we were able to refine the COPE tool to provide the key elements they desired including pertinent patient medical information, checklist for planning when seeking urgent care, and coordination of care with the medical team and other caregivers.
(©2020 AMIA - All rights reserved.)

Primate models are important for understanding human conditions, especially in studies of ageing, pathology, adaptation, and evolution. However, how to integrate data from multiple disciplines and render them compatible with each other for datamining and in-depth study is always challenging. In a long-term project, we have started a collaborative research endeavor to examine the health history of a free-ranging rhesus macaque colony at Cayo Santiago, and build a knowledge model for anthropological and biomedical/translational studies of the effects of environment and genetics on bone development, aging, and pathologies. This paper discusses the conceptual design as well as the prototyping of this model and related graphical user interfaces, and how these will help future scientific queries and studies.

Equipment Design, Industry, Lab-On-A-Chip Devices, and Printing, Three-Dimensional instrumentation

Microfluidic technologies have enormous potential to offer breakthrough solutions across a wide range of applications. However, the rate of scale-up and commercialization of these technologies has lagged significantly behind promising breakthrough developments in the lab, due at least in part to the problems presented by transitioning from benchtop fabrication methods to mass-manufacturing. In this work, we develop and validate a method to create functional microfluidic prototype devices using 3D printed masters in an industrial-scale roll-to-roll continuous casting process. There were no significant difference in mixing performance between the roll-to-roll cast devices and the PDMS controls in fluidic mixing tests. Furthermore, the casting process provided information on the suitability of the prototype microfluidic patterns for scale-up. This work represents an important step in the realization of high-volume prototyping and manufacturing of microfluidic patterns for use across a broad range of applications.

Powered ankle-foot prostheses for walking often have limitations in the range of motion and in push-off power, if compared to a lower limb of a healthy person. A new design of a powered ankle-foot prosthesis is proposed to obtain a wide range of motion and an adequate power for a push-off step. The design methodology for this prosthesis has three points. In the first one, a dimensionless kinematic model of the lower limb in the sagittal plane is built, through an experimental campaign with healthy subjects, to calculate the angles of lower limb during the gait. In the second point a multibody inverse dynamic model of the lower limb is constructed to calculate the foot-ground contact force, its point of application and the ankle torque too, entering as input data the calculated angles of the lower limb in the previous point. The third point requires, as input of the inverse dynamic model, the first dimensioning data of the ankle-foot prosthesis to obtain the load acting on the components of the prosthesis and the angle torque of the actuator during the gait cycle. Finally, an iteration cycle begins with the inverse dynamic model modifying the ankle torque and angle until these quantities during the gait are as close as possible to the physiological quantities. After the mechanical design and the construction of the prototype of the prosthesis, an experimental methodology was used for preliminary validation of the design. The preliminary tests in the laboratory on the prototype alone show that the range of motion of the ankle angle during the gait is close to a healthy person's: 27.6° vs. 29°. The pushing force of the distal area of the prototype is 1.000 N, instead of 1.600 N, because a budget reduction forced us to choose components for the prototype with lower performance.

Tomography, X-Ray Computed, Contrast Media, and Printing, Three-Dimensional

The objective of this study was to evaluate a method for printing a custom radiocontrast agent mixture to develop computed tomography markers of various shapes and sizes for assisting physicians in computed tomography-guided procedures. The radiocontrast agent mixture was designed to be bright in a computed tomography image, able to be extruded from a nozzle as a liquid and transition into a solid, and sufficiently viscous to be extruded through the tip of a needle in a controlled manner. A mixture printing method was developed using a syringe to house the mixture, a syringe pump to extrude the mixture, and a computer numeric control laser cutter to direct the nozzle in the desired path. To assess the efficacy of printing the radiocontrast agent mixture, we printed several designs, collected computed tomography images, and evaluated various physical properties of the printing method and the resulting computed tomography markers. The average line thickness was 1.56 mm (standard deviation of 0.19 mm, n = 30), the infill percentage was 99.9%, and the deviation in roundness was 0.23 mm ( n = 30). These results demonstrated the ability of the proposed method to create various types of skin markers, such as dots, lines, and hollow or solid shapes. Additionally, flat printed patterns can be folded to form three-dimensional structures that can be used to guide and support needle insertions.

Ankle, Ankle Joint, Biomechanical Phenomena, Foot, Gait, Humans, Prosthesis Design, Walking, and Artificial Limbs

This article presents a novel design of a prosthetic foot that features adaptable stiffness that changes according to the speed of ankle motion. The motivation is the natural graduation in stiffness of a biological ankle over a range of ambulation tasks. The device stiffness depends on rate of movement, ranging from a dissipating support at very slow walking speed, to efficient energy storage and return at normal walking speed. The objective here is to design a prosthetic foot that provides a compliant support for slow ambulation, without sacrificing the spring-like energy return beneficial in normal walking. The design is a modification of a commercially available foot and employs material properties to provide a change in stiffness. The velocity dependent properties of a non-Newtonian working fluid provide the rate adaptability. Material properties of components allow for a geometry shift that results in a coupling action, affecting the stiffness of the overall system. The function of an adaptive coupling was tested in linear motion. A prototype prosthetic foot was built, and the speed dependent stiffness measured mechanically. Furthermore, the prototype was tested by a user and body kinematics measured in gait analysis for varying walking speed, comparing the prototype to the original foot model (non-modified). Mechanical evaluation of stiffness shows increase in stiffness of about 60% over the test range and 10% increase between slow and normal walking speed in user testing.