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Three-dimensional printing (3DP) technology is a rapid prototyping technology that is widely used in the medical field. It can be combined with computer-aided design, material manufacturing, and other technologies to construct medical-related appliances, human implants and even cell-based models or biological tissues. In the field of ophthalmology, the technology can be used to manufacture ocular anatomical models, glasses, intraocular implants, microsurgical instruments, drugs, etc. It can also enable future 'bioprinting', involving the refractive and nervous systems of the eyeball, with excellent development prospects in the field. This review introduces the development of 3DP technology in ophthalmology and discusses its application and potential.
(© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Printing, Three-Dimensional, Hydrogen Peroxide, and Luminescence

Low force stereolithography is exploited for the first time for one-step facile fabrication of chemiluminescence (CL) flow-through cells that bear unrivalled features as compared to those available through milling or blowing procedures or alternative 3D printing technologies. A variety of bespoke cross-section geometries with polyhedral features (namely, triangular, square, and five-side polygon) as well as semicircular cross-section are herein critically evaluated in terms of analytical performance against the standardcircular cross-section in a flat spirally-shape format. The idea behind is to maximize capture of elicited light by the new designs while leveraging 3D printing further for fabrication of (i) customized gaskets that enable reliable attaching of the active mixing zone of the CL cell to the detection window, (ii) in-line 3D-printed serpentine reactors, and (iii) flow confluences with tailorable shapes for enhancing mixing of samples with CL reagents. Up to twenty transparent functional cells were simultaneously fabricated without inner supports following post-curing and surface treatment protocols lasting less than 5 h. In fact, previous attempts to print spirally-shaped cells in one-step by resorting to less cost effective photopolymer inkjet printing technologies were unsuccessful because of the requirement of lengthy procedures (>15 days) for quantitative removal of the support material. By exploiting the phthalazinedione-hydrogen peroxide chemistry as a model reaction, the five-side irregular pentagon cell exhibited superior analytical figures of merit in terms of LOD, dynamic range and intermediate precision as compared to alternative designs. Computational fluid dynamic simulations for mapping velocities at the entry region of the spiral cell corroborated the fact that the 5-side polygon cross-section flow-cell with Y-type confluence permitted the most efficient mixing of reagents and sample while enabling larger flow velocities near the inlet that contribute to a more efficient capture of the photons from the flash-type reaction. The applicability of the 3D-printed 5-side polygon CL cell for automatic determination of hydrogen peroxide using a computerized hybrid flow system was demonstrated for the analysis of high matrix samples, viz., seawater and saliva, with relative recoveries ranging from 83 to 103%.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier B.V. All rights reserved.)

Humans, Organs at Risk, Image Processing, Computer-Assisted methods, and Tomography, X-Ray Computed methods

Background and Objective: Despite fast evolution cycles in deep learning methodologies for medical imaging in radiotherapy, auto-segmentation solutions rarely run in clinics due to the lack of open-source frameworks feasible for processing DICOM RT Structure Sets. Besides this shortage, available open-source DICOM RT Structure Set converters rely exclusively on 2D reconstruction approaches leading to pixelated contours with potentially low acceptance by healthcare professionals. PyRaDiSe, an open-source, deep learning framework independent Python package, addresses these issues by providing a framework for building auto-segmentation solutions feasible to operate directly on DICOM data. In addition, PyRaDiSe provides profound DICOM RT Structure Set conversion and processing capabilities; thus, it applies also to auto-segmentation-related tasks, such as dataset construction for deep learning model training.
Methods: The PyRaDiSe package follows a holistic approach and provides DICOM data handling, deep learning model inference, pre-processing, and post-processing functionalities. The DICOM data handling allows for highly automated and flexible handling of DICOM image series, DICOM RT Structure Sets, and DICOM registrations, including 2D-based and 3D-based conversion from and to DICOM RT Structure Sets. For deep learning model inference, extending given skeleton classes is straightforwardly achieved, allowing for employing any deep learning framework. Furthermore, a profound set of pre-processing and post-processing routines is included that incorporate partial invertibility for restoring spatial properties, such as image origin or orientation.
Results: The PyRaDiSe package, characterized by its flexibility and automated routines, allows for fast deployment and prototyping, reducing efforts for auto-segmentation pipeline implementation. Furthermore, while deep learning model inference is independent of the deep learning framework, it can easily be integrated into famous deep learning frameworks such as PyTorch or Tensorflow. The developed package has successfully demonstrated its capabilities in a research project at our institution for organs-at-risk segmentation in brain tumor patients. Furthermore, PyRaDiSe has shown its conversion performance for dataset construction.
Conclusions: The PyRaDiSe package closes the gap between data science and clinical radiotherapy by enabling deep learning segmentation models to be easily transferred into clinical research practice. PyRaDiSe is available on https://github.com/ubern-mia/pyradise and can be installed directly from the Python Package Index using pip install pyradise.
Competing Interests: Declaration of Competing Interest Authors declare that they have no conflict of interest.
(Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Humans, Medication Systems, Hospital, Patient Safety, Medication Therapy Management, and Medical Order Entry Systems

Introduction: Poorly designed electronic medication management systems (EMMS) or computerized physician order entry (CPOE) systems in hospital settings can result in usability issues and in turn, patient safety risks. As a safety science, human factors and safety analysis methods have potential to support the safe and usable design of EMMS.
Objective: To identify and describe human factors and safety analysis methods that have been used in the design or redesign of EMMS used in hospital settings.
Materials and Methods: A systematic review, following PRISMA guidelines, was conducted by searching online databases and relevant journals from January 2011 to May 2022. Studies were included if they described the practical application of human factors and safety analysis methods to support the design or redesign of a clinician-facing EMMS, or its components. Methods used were extracted and mapped to human centered design (HCD) activities: understanding context of use; specifying user requirements; producing design solutions; and evaluating the design.
Results: Twenty-one papers met the inclusion criteria. Overall, 21 human factors and safety analysis methods were used in the design or redesign of EMMS with prototyping, usability testing, participant surveys/questionnaires and interviews the most frequent. Human factors and safety analysis methods were most frequently used to evaluate the design of a system (n = 67; 56.3%). Nineteen of 21 (90%) methods used aimed to identify usability issues and/or support iterative design; only one paper utilized a safety-oriented method and one, a mental workload assessment method.
Discussion and Conclusion: While the review identified 21 methods, EMMS design primarily utilized a subset of available methods, and rarely a method focused on safety. Given the high-risk nature of medication management in complex hospital environments, and the potential for harm due to poorly designed EMMS, there is significant potential to apply more safety-oriented human factors and safety analysis methods to support EMMS design.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

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

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

Brain diagnostic imaging, Algorithms, Image Processing, Computer-Assisted methods, Magnetic Resonance Imaging methods, and Software

Purpose: Introduce Shimming Toolbox ( https://shimming-toolbox.org), an open-source software package for prototyping new methods and performing static, dynamic, and real-time B0 shimming as well as B1 shimming experiments.
Methods: Shimming Toolbox features various field mapping techniques, manual and automatic masking for the brain and spinal cord, B0 and B1 shimming capabilities accessible through a user-friendly graphical user interface. Validation of Shimming Toolbox was demonstrated in three scenarios: (i) B0 dynamic shimming in the brain at 7T using custom AC/DC coils, (ii) B0 real-time shimming in the spinal cord at 3T, and (iii) B1 static shimming in the spinal cord at 7T.
Results: The B0 dynamic shimming of the brain at 7T took about 10 min to perform. It showed a 47% reduction in the standard deviation of the B0 field, associated with noticeable improvements in geometric distortions in EPI images. Real-time dynamic xyz-shimming in the spinal cord took about 5 min and showed a 30% reduction in the standard deviation of the signal distribution. B1 static shimming experiments in the spinal cord took about 10 min to perform and showed a 40% reduction in the coefficient of variation of the B1 field.
Conclusion: Shimming Toolbox provides an open-source platform where researchers can collaborate, prototype and conveniently test B0 and B1 shimming experiments. Future versions will include additional field map preprocessing techniques, optimization algorithms, and compatibility across multiple MRI manufacturers.
(© 2022 International Society for Magnetic Resonance in Medicine.)

There has been a compelling demand of fabricating high-resolution complex three-dimensional (3D) structures in nanotechnology. While two-photon lithography (TPL) largely satisfies the need since its introduction, its low writing speed and high cost make it impractical for many large-scale applications. We report a digital holography-based TPL platform that realizes parallel printing with up to 2000 individually programmable laser foci to fabricate complex 3D structures with 90 nm resolution. This effectively improves the fabrication rate to 2,000,000 voxels/sec. The promising result is enabled by the polymerization kinetics under a low-repetition-rate regenerative laser amplifier, where the smallest features are defined via a single laser pulse at 1 kHz. We have fabricated large-scale metastructures and optical devices of up to centimeter-scale to validate the predicted writing speed, resolution, and cost. The results confirm our method provides an effective solution for scaling up TPL for applications beyond laboratory prototyping.
(© 2023. The Author(s).)

Background: Botswana, like most sub-Sahara African nations, uses conventional orthopaedic implants that are sourced from major manufactures in the West. The implants are mass-produced and designed with universal configurations to fit an average patient. During surgery, surgeons thus sometimes bend the implants to match the individual bone anatomy, especially for paediatric patients and those with unique deformities, thus risking implant failure. The purpose of this project was to show the feasibility of developing safe and effective patient-specific orthopaedic implants in a low-resourced market.
Methods: CT Scan slice files of a paediatric patient with Ollier's disease were used to reconstruct the lower limb anatomy. The resultant files were 3D printed into prototypes that showed severe right knee valgus deformity. The surgeon used the prototype to plan for corrective femoral osteotomy and the required implant. The implant design and planned surgery were subsequently simulated on the Medical Design Studio software for proper fitting before final implant printing. Surgery was then performed, followed by 12 weeks of physiotherapy.
Results: Post-surgical x-rays demonstrated good implant positioning and knee joint alignment. At 18 months of post-surgical follow-up, the child was pain-free, could perform full squats, and ambulation was near-normal, without the use of an assistive device.
Conclusions: It is feasible to develop effective, patient-specific implants for selected orthopaedic cases in a low-resourced country. This work could improve surgical and rehabilitation outcomes for selected paediatric patients and those with severe bone deformities.
(© 2023. The Author(s).)

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

Background: Electronic paper (E-paper) screens use electrophoretic ink to provide paper-like low-power displays with advanced networking capabilities that may potentially serve as an alternative to traditional whiteboards and television display screens in hospital settings. E-paper may be leveraged in the emergency department (ED) to facilitate communication. Providing ED patient status updates on E-paper screens could improve patient satisfaction and overall experience and provide more equitable access to their health information.
Objective: We aimed to pilot a patient-facing digital whiteboard using E-paper to display relevant orienting and clinical information in real time to ED patients. We also sought to assess patients' satisfaction after our intervention and understand our patients' overall perception of the impact of the digital whiteboards on their stay.
Methods: We deployed a 41-inch E-paper digital whiteboard in 4 rooms in an urban, tertiary care, and academic ED and enrolled 110 patients to understand and evaluate their experience. Participants completed a modified Hospital Consumer Assessment of Health Care Provider and Systems satisfaction questionnaire about their ED stay. We compared responses to a matched control group of patients triaged to ED rooms without digital whiteboards. We designed the digital whiteboard based on iterative feedback from various departmental stakeholders. After establishing IT infrastructure to support the project, we enrolled patients on a convenience basis into a control and an intervention (digital whiteboard) group. Enrollees were given a baseline survey to evaluate their comfort with technology and an exit survey to evaluate their opinions of the digital whiteboard and overall ED satisfaction. Statistical analysis was performed to compare baseline characteristics as well as satisfaction.
Results: After the successful prototyping and implementation of 4 digital whiteboards, we screened 471 patients for inclusion. We enrolled 110 patients, and 50 patients in each group (control and intervention) completed the study protocol. Age, gender, and racial and ethnic composition were similar between groups. We saw significant increases in satisfaction on postvisit surveys when patients were asked about communication regarding delays (P=.03) and what to do after discharge (P=.02). We found that patients in the intervention group were more likely to recommend the facility to family and friends (P=.04). Additionally, 96% (48/50) stated that they preferred a room with a digital whiteboard, and 70% (35/50) found the intervention "quite a bit" or "extremely" helpful in understanding their ED stay.
Conclusions: Digital whiteboards are a feasible and acceptable method of displaying patient-facing data in the ED. Our pilot suggested that E-paper screens coupled with relevant, real-time clinical data and packaged together as a digital whiteboard may positively impact patient satisfaction and the perception of the facility during ED visits. Further study is needed to fully understand the impact on patient satisfaction and experience.
Trial Registration: ClinicalTrials.gov NCT04497922; https://clinicaltrials.gov/ct2/show/NCT04497922.
(©Andrew D A Marshall, Mohammad Adrian Hasdianda, Steven Miyawaki, Guruprasad D Jambaulikar, Chenze Cao, Paul Chen, Christopher W Baugh, Haipeng Zhang, Jonathan McCabe, Lee Steinbach, Scott King, Jason Friedman, Jennifer Su, Adam B Landman, Peter Ray Chai. Originally published in JMIR Formative Research (https://formative.jmir.org), 21.03.2023.)

Cell Extracts, Freezing, Saccharomyces cerevisiae metabolism, and Bacteria

Cell-free synthetic biology enables rapid prototyping of biological parts and synthesis of proteins or metabolites in the absence of cell growth constraints. Cell-free systems are frequently made from crude cell extracts, where composition and activity can vary significantly based on source strain, preparation and processing, reagents, and other considerations. This variability can cause extracts to be treated as black boxes for which empirical observations guide practical laboratory practices, including a hesitance to use dated or previously thawed extracts. To better understand the robustness of cell extracts over time, we assessed the activity of cell-free metabolism during storage. As a model, we studied conversion of glucose to 2,3-butanediol. We found that cell extracts from Escherichia coli and Saccharomyces cerevisiae subjected to an 18-month storage period and repeated freeze-thaw cycles retain consistent metabolic activity. This work gives users of cell-free systems a better understanding of the impacts of storage on extract behavior.

Background: User involvement is widely accepted as key for designing effective applied games for health. This especially holds true for children and young people as target audiences, whose abilities, needs, and preferences can diverge substantially from those of adult designers and players. Nevertheless, there is little shared knowledge about how concretely children and young people have been involved in the design of applied games, let alone consensus guidance on how to do so effectively.
Objective: The aim of this scoping review was to describe which user involvement methods have been used in the design of applied games with children and young people, how these methods were implemented, and in what roles children and young people were involved as well as what factors affected their involvement.
Methods: We conducted a systematic literature search and selection across the ACM Digital Library, IEEE Xplore, Scopus, and Web of Science databases using State of the Art through Systematic Review software for screening, selection, and data extraction. We then conducted a qualitative content analysis on the extracted data using NVivo.
Results: We retrieved 1085 records, of which 47 (4.33%) met the eligibility criteria. The chief involvement methods were participatory design (20/47, 43%) and co-design (16/47, 37%), spanning a wide range of 45 concrete activities with paper prototyping, group discussions, and playtesting being the most frequent. In only half of the studies (24/47, 51%), children and young people participated as true design partners. Our qualitative content analysis suggested 5 factors that affect their successful involvement: comprehension, cohesion, confidence, accessibility, and time constraints.
Conclusions: Co-design, participatory design, and similar high-level labels that are currently used in the field gloss over very uneven degrees of participation in design and a wide variety of implementations that greatly affect actual user involvement. This field would benefit from more careful consideration and documentation of the reason of user involvement. Future research should explore concrete activities and configurations that can address the common challenges of involving children and young people, such as comprehension, cohesion, confidence, and accessibility.
(©Michael John Saiger, Sebastian Deterding, Lina Gega. Originally published in JMIR Serious Games (https://games.jmir.org), 16.03.2023.)

Purpose of Review: Digital (i.e., online, mobile) interventions have potential to increase access to care for people with eating disorders, but engagement with digital interventions has been challenging. Human-centered design is a methodology that centralizes the design of technologies on the people who will be using them and the settings in which they will be implemented, to yield solutions with high engagement and clinical impact. The paper presents an overview of the human-centered design process, followed by a review of publications that have applied design methods to digital interventions for eating disorders.
Recent Findings: Design research has been conducted via needs assessments, prototyping and usability studies, and during ongoing delivery of digital eating disorder interventions. There has been growing research applying design methods to digital interventions for eating disorders. Additional opportunities include designing for implementation, designing for equity, and designing for the optimization of digital interventions over time.
(© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Vanadium dioxide (VO 2 ) is widely employed in developing tunable optoelectronic devices due to its significant changes in optical and electric properties upon phase transition. To fabricate the VO 2 -based functional devices down to the micro/nanoscale, a high-resolution processing technique is in demand. Scanning probe lithography (SPL) on the basis of a tip-induced electric field provides a promising approach for prototyping. Here, we demonstrated a precise VO 2 etching strategy by direct writing on a VO 2 film with a negative tip bias and subsequent sonication removal of the written area. The effects of bias voltage, sonication, and thermal treatment as well as the mechanical difference between the tip-modulated area and the pristine VO 2 film were investigated systematically. The results show that VO 2 can be etched layer by layer via alternately repeating tip modulation and sonication, and arbitrary patterns can be written. Based on this route, we designed a kind of metasurface by arranging VO 2 -gold nanoblocks with different sizes and heights for spectrally selective tunable reflectivity in near- and mid-infrared. This electric-field SPL method demonstrates the prominent advantages of high resolution down to several tens of nanometers, quasi-3D patterning, and resist-free maskless direct writing, which should be applicable for prototyping other micro/nanodevices.

In an experiment so-termed sociotechnical prototypes based on either a graphical or a textual representation of an envisioned work system were evaluated with regard to their ability to communicate a design vision to people involved in a participatory design process. Results of the study reveal, in line with hypotheses, that the graphical prototype, in contrast to the textual one, was significantly better accepted as well as faster explored and evaluated. Moreover, results support the hypothesis that the graphical sociotechnical prototype helps to build up a more accurate mental representation of the system with regard to its elements (e.g. job roles, tasks). However, no positive effect on the mental representation of the system in terms of the relations between its elements (e.g. which role performs which task?) was found. Finally, practical implications and perspectives for further development of the sociotechnical prototyping approach to envision future work systems are discussed.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier Ltd. All rights reserved.)

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

Background: Monte Carlo particle simulation has become the primary tool for designing low-energy miniature x-ray tubes due to the difficulties of physically prototyping these devices and characterizing their radiation fields. Accurate simulation of electronic interactions within their targets is necessary for modeling both photon production and heat transfer. Voxel-averaging can conceal hot spots in the target heat deposition profile that can threaten the integrity of the tube.
Purpose: This research seeks a computationally-efficient method of estimating voxel-averaging error in energy deposition simulations of electron beams penetrating thin targets to inform the appropriate scoring resolution for a desired accuracy level.
Methods: An analytical model to estimate voxel-averaging along the target depth was developed and compared to results from Geant4 via its wrapper, TOPAS. A 200 keV planar electron beam was simulated to impinge tungsten targets of thicknesses between 1.5- and 12.5- μ m ${{\umu {\rm m}}}$ . For each target, the model was used to calculate the energy deposition ratio between voxels of varying sizes centered on the longitudinal midpoint of the target. Model-calculated ratios were compared to simulation outputs to gauge the model's accuracy. Then, the model was used to approximate the error between the point value of electron energy deposition and a voxel-based measurement.
Results: The model underestimates error to within 5% for targets less than 7.5- μ m ${{\umu {\rm m}}}$ in thickness with increasing error for greater thicknesses. For the 1.5- μ m ${{\umu {\rm m}}}$ target, calculations of the point-vs.-voxel energy deposition show an 11% averaging effect between the midpoint and a 1.5- μ m ${{\umu {\rm m}}}$ voxel. Energy deposition profiles along the target depth were also calculated in the Monte Carlo for reference.
Conclusion: A simple analytical model was developed with reasonable accuracy to guide Monte Carlo users in estimating the appropriate depth-voxel size for thin-target x-ray tube simulations. This methodology can be adapted for other radiological contexts to increase robustness in point-value estimations.
(© 2023 American Association of Physicists in Medicine.)

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

Robotics methods and Robotics trends

Since its beginnings in the 1960s, soft robotics has been a steadily growing field that has enjoyed recent growth with the advent of rapid prototyping and the provision of new flexible materials. These two innovations have enabled the development of fully flexible and untethered soft robotic systems. The integration of novel sensors enabled by new manufacturing processes and materials shows promise for enabling the production of soft systems with 'embodied intelligence'. Here, four experts present their perspectives for the future of the field of soft robotics based on these past innovations. Their focus is on finding answers to the questions of: how to manufacture soft robots, and on how soft robots can sense, move, and think. We highlight industrial production techniques, which are unused to date for manufacturing soft robots. They discuss how novel tactile sensors for soft robots could be created to enable better interaction of the soft robot with the environment. In conclusion this article highlights how embodied intelligence in soft robots could be used to make soft robots think and to make systems that can compute, autonomously, from sensory inputs.
(Creative Commons Attribution license.)

Statement of Problem: Providing a removable partial denture (RPD) can be a complex, time-consuming, and error-prone procedure. Computer-aided design and computer-aided manufacturing (CAD-CAM) techniques have shown promising clinical outcomes; however, the influence of manufacturing techniques on the properties of RPD components is unclear.
Purpose: The purpose of this systematic review was to determine the accuracy and mechanical properties of RPD components fabricated with conventional and digital methods.
Material and Methods: This study followed the guidelines of the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) and was registered on the international prospective register of systematic reviews (PROSPERO) database (CRD42022353993). An electronic search was conducted on PubMed/MEDLINE, Scopus, Web of Science, and the Cochrane Library in August 2022. Only in vitro studies comparing the digital with the lost-wax casting technique were included. The quality of the studies was assessed by using the methodological index for nonrandomized studies (MINORS) scale.
Results: Of the 17 selected studies, 5 evaluated the accuracy of RPD components as well as the mechanical properties, 5 studies evaluated only the component accuracy, and another 7 evaluated only the mechanical properties. The accuracy was similar regardless of the technique, with discrepancies within clinically acceptable values (50 to 426.3 μm). The surface roughness was higher for 3D-printed clasps and lower for milled clasps (P<.05). The metal alloy significantly influenced the porosity, with the highest number of pores obtained by casting for Ti clasps and by rapid prototyping for Co-Cr clasps.
Conclusions: In vitro studies showed that the digital technique provided similar accuracy to that of the conventional technique within a clinically acceptable range. The manufacturing technique influenced the mechanical properties of RPD components.
(Copyright © 2023 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

The 3D-printing technology has emerged as a well-developed method to produce parts with considerably low cost and yet with high precision (<100 μm). Recent literature has shown that the 3D-printing technology can be exploited to fabricate a magic-angle spinning (MAS) system in solid-state nuclear magnetic resonance (NMR) spectroscopy. In particular, it was demonstrated that advanced industry-grade 3D printers could fabricate 3.2 mm MAS drive caps with intricate features, and the caps were shown to spin > 20 kHz. Here, we show that not only lab-affordable benchtop 3D printers can produce 3.2 mm drive caps with a similar quality as the commercialized version, but also smaller 2.5 mm and 1.3 mm MAS drive caps-despite a slight compromise in performance. All in-house fabricated drive caps (1.3 to 7 mm) can be consistently reproduced (>90 %) and achieve excellent spinning performances. In summary, the > 3.2 mm systems have similar performances as the commercial systems, while the 2.5- and 1.3-mm caps can spin up to 26 kHz ± 2 Hz, and 46 kHz ± 1 Hz, respectively. The low-cost and fast in-house fabrication of MAS drive caps allows easy prototyping of new MAS drive cap models and, possibly, new NMR applications. For instance, we have fabricated a 4 mm drive cap with a center hole that could allow better light penetration or sample insertion during MAS. Besides, an added groove design on the drive cap allows an airtight seal suitable for probing air- or moisture-sensitive materials. Moreover, the 3D-printed cap was shown to be robust for low-temperature MAS experiments at ∼ 100 K, making it suitable for DNP experiments.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier Inc. All rights reserved.)

Humans, Creatinine chemistry, Limit of Detection, Smartphone, Electrochemical Techniques, Electrodes, Graphite chemistry, and Nanoparticles chemistry

3D printing technologies are an attractive for fabricating electrochemical sensors due to their ease of operation, freedom of design, fast prototyping, low waste, and low cost. We report the fabrication of a simple 3D-printed electrochemical sensing device for non-enzymatic detection of creatinine, an important indicator of renal function. To create the 3D-printed electrodes (3DE), carbon black/polylactic acid (CB/PLA) composite filament was used. The 3DE was activated using 0.5 M NaOH via amperometry prior to use to improve electrochemical performance. To give selectivity for creatinine, the activated 3DE was modified with a copper oxide nanoparticle-ionic liquid/reduced graphene oxide (CuO-IL/rGO) composite. The modified 3DE was characterized using microscopy and electrochemistry. Cyclic voltammetry and amperometry were used to evaluate sensor performance. The modified 3DE provided electrocatalytic activity towards creatinine without enzymes. Under optimal conditions, the modified 3DE directly coupled with a portable smartphone potentiostat exhibited the linear detection range of 0.5-35.0 mM, and the limit of detection was 37.3 μM, which is sufficient for detecting creatinine in human urine samples. Furthermore, the other physiological compounds present in human urine were not detected on the modified 3DE. Therefore, the modified 3DE could be a tool for effective creatinine screening in the urine.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2022 Elsevier B.V. All rights reserved.)

Humans, Freeze Drying methods, Pharmaceutical Preparations, Antibodies, Monoclonal chemistry, Chemistry, Pharmaceutical methods, and Desiccation

To improve the long-term stability of drugs with limited stability (e.g., biologicals such as monoclonal antibodies, antibody drug conjugates or peptides), some pharmaceuticals endure a lengthy and cost-intensive process called lyophilization. While the shelf life of lyophilized drugs may be prolonged compared to their liquid form, the drawbacks come in the form of intensified manufacturing, preparation, and dosing efforts. The use of glass vials as the primary container unit for lyophilized products hinders their complication-free, fast and flexible use, as they require a skilled healthcare professional and an aseptic environment in which to prepare them. The feasibility of substituting glass vials with novel container designs offering the complete transfer of the lyophilizate cake into modern administration devices, while reducing the economic footprint of the lyophilization process, was investigated. The lyophilization process of a monoclonal antibody solution was studied by assessing primary drying conditions, homogeneity of the drying process, and critical quality attributes after successful lyophilization. The creation of novel container designs utilized vacuum-forming to generate confined containers with removable bottoms and rapid prototyping, including subtractive and additive manufacturing methods, to generate porous 3D structures for drug housing. The novel container designs generated lyophilizates twice as fast and achieved a threefold faster reconstitution compared to their vial counterparts, without adaptation of the processing conditions. We conclude that the use of intermediate process containers offers significant relief for healthcare professionals in terms of reduced probability of handling errors, while drug manufacturers benefit from the accelerated processing times, increased batch homogeneity, and sustainability.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2022. Published by Elsevier B.V.)

Humans, Focus Groups, Education, Pharmacy, and Pharmacy

Objective. To describe and evaluate how a design thinking approach aided the creation of the 2021 American Association of Colleges of Pharmacy (AACP) Teachers' Seminar. Methods. The design thinking framework (ie, inspiration, ideation, and implementation) was used to structure the seminar development process from July 2020 to July 2021. Nine committee members engaged in a persona activity (ie, inspiration), a brainstorming activity (ie, ideation), and a prototyping activity (ie, implementation) to create a user-centered learning experience. Twenty-five small group facilitators were then recruited to create and deliver breakout session content. After the seminar, the team was invited to debrief their experience in a focus group and an electronic survey to evaluate the perceived impact of using design thinking in the planning process. Results. Twenty-one (62%) of the 34 committee members and small group facilitators attended the focus group, and 28 (82%) completed the electronic survey. Most agreed that design thinking was a useful approach to support the Teachers' Seminar, and they were generally positive about the experience. There was a significant increase in self-reported creative self-efficacy for coming up with novel ideas, ability to solve problems, and helping expand others' ideas. Team members identified positive attributes about the seminar and planning process as well as areas for improvement. Team members also acknowledged challenges and potential solutions for professional organizations and program developers to consider when creating user-centered experiences. Conclusion. Design thinking can be a useful framework for seminar planning and implementation to create engaging, meaningful, and valuable educator development experiences.
(© 2023 American Association of Colleges of Pharmacy.)

Ethanol metabolism, Models, Biological, Kinetics, Butanols metabolism, and 1-Butanol

Cell-free systems are useful tools for prototyping metabolic pathways and optimizing the production of various bioproducts. Mechanistically-based kinetic models are uniquely suited to analyze dynamic experimental data collected from cell-free systems and provide vital qualitative insight. However, to date, dynamic kinetic models have not been applied with rigorous biological constraints or trained on adequate experimental data to the degree that they would give high confidence in predictions and broadly demonstrate the potential for widespread use of such kinetic models. In this work, we construct a large-scale dynamic model of cell-free metabolism with the goal of understanding and optimizing butanol production in a cell-free system. Using a combination of parameterization methods, the resultant model captures experimental metabolite measurements across two experimental conditions for nine metabolites at timepoints between 0 and 24 h. We present analysis of the model predictions, provide recommendations for butanol optimization, and identify the aldehyde/alcohol dehydrogenase as the primary bottleneck in butanol production. Sensitivity analysis further reveals the extent to which various parameters are constrained, and our approach for probing valid parameter ranges can be applied to other modeling efforts.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.)

Male, Humans, Sentinel Lymph Node Biopsy methods, Optical Imaging, Indocyanine Green, Lymph Nodes, Sentinel Lymph Node diagnostic imaging, Prostatic Neoplasms diagnostic imaging, and Prostatic Neoplasms surgery

Humans, Printing, Three-Dimensional, Surgery, Plastic, Dental Implants, Plastic Surgery Procedures, and Surgery, Computer-Assisted methods

Rapid developments in 3-dimensional(3D) printing technologies in craniofacial plastic surgery have provided a new treatment modality for patients. In this article, we intend to share our institution's experience using 3D printing in 3 modes-namely, 3-dimensional printing for manufacturing contour models, guides, and implants. Fifty-nine patients were enrolled in our study between September 2009 and September 2021. Among the 3D printing-assisted technologies, 41 cases were used for congenital malformations, 82 for trauma repair, and 112 for cosmetic surgery. Preoperative design and postoperative data were compared and analyzed based on imaging data. In craniofacial plastic surgery, all patients had excellent postoperative objective bone measurements close to the preoperative design and improved esthetic appearance. Our survey of postoperative satisfaction showed that patients were quite satisfied with the surgery, especially concerning congenital deformities. Rapid prototyping 3-dimensional printing technology provides a practical and anatomically accurate means to produce patient-specific and disease-specific translational tools. These models can be used for surgical planning, simulation, and clinical evaluation. Expanding this technology in craniofacial plastic surgery will provide adequate assistance to practitioners and patients.
Competing Interests: The authors report no conflicts of interest.
(Copyright © 2023 by Mutaz B. Habal, MD.)

The ability to construct multiplexed micro-systems for fluid regulation could substantially impact multiple fields, including chemistry, biology, biomedicine, tissue engineering, and soft robotics, among others. 3D printing is gaining traction as a compelling approach to fabricating microfluidic devices by providing unique capabilities, such as 1) rapid design iteration and prototyping, 2) the potential for automated manufacturing and alignment, 3) the incorporation of numerous classes of materials within a single platform, and 4) the integration of 3D microstructures with prefabricated devices, sensing arrays, and nonplanar substrates. However, to widely deploy 3D printed microfluidics at research and commercial scales, critical issues related to printing factors, device integration strategies, and incorporation of multiple functionalities require further development and optimization. In this review, we summarize important figures of merit of 3D printed microfluidics and inspect recent progress in the field, including ink properties, structural resolutions, and hierarchical levels of integration with functional platforms. Particularly, we highlight advances in microfluidic devices printed with thermosetting elastomers, printing methodologies with enhanced degrees of automation and resolution, and the direct printing of microfluidics on various 3D surfaces. The substantial progress in the performance and multifunctionality of 3D printed microfluidics suggests a rapidly approaching era in which these versatile devices could be untethered from microfabrication facilities and created on demand by users in arbitrary settings with minimal prior training.

Purpose: to evaluate the efficacy of dual-purpose computer-generated splint in guiding the proximal and the distal segment in bilateral sagittal split osteotomy.
Patients and Method: It was a prospective case series study directed on 8 class III patients indicating the need of maxillary advancement and mandibular set back by bilateral sagittal split osteotomy. A CAD/CAM splint is generated to guide the distal segment to the stable maxilla and at the same time a grooved extension to engage the proximal segment ensuring the condyle in its planned position during fixation. The primary outcome was measured by calculating the difference between the pre- and post-operative condylar segment position.
Results: The present study included five female patient and three male patient with mean age of 28.4 ± 5.1 years. The accuracy of the splint in positioning the mandibular proximal segment showed promising results ranging from 2.59 to 0.49.
Conclusion: The dual-purpose splint introduced in this study showed satisfied results in maintaining the pre-operative condylar position while securing the distal segment in the desired plan.
Competing Interests: Conflict of interestThe authors declare that there is no conflict of interest (Mamdouh Ahmed declares that there is no conflict of interest, Sherif Ali declares that there is no conflict of interest and Sara Soliman declares that there is no conflict of interest).
(© This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply 2022.)

Nucleic Acid Conformation, DNA chemistry, Nanotechnology methods, and Nanostructures chemistry

Living systems achieve robust self-assembly across a wide range of length scales. In the synthetic realm, nanofabrication strategies such as DNA origami have enabled robust self-assembly of submicron-scale shapes from a multitude of single-stranded components. To achieve greater complexity, subsequent hierarchical joining of origami can be pursued. However, erroneous and missing linkages restrict the number of unique origami that can be practically combined into a single design. Here we extend crisscross polymerization, a strategy previously demonstrated with single-stranded components, to DNA-origami 'slats' for fabrication of custom multi-micron shapes with user-defined nanoscale surface patterning. Using a library of ~2,000 strands that are combinatorially arranged to create unique DNA-origami slats, we realize finite structures composed of >1,000 uniquely addressable slats, with a mass exceeding 5 GDa, lateral dimensions of roughly 2 µm and a multitude of periodic structures. Robust production of target crisscross structures is enabled through strict control over initiation, rapid growth and minimal premature termination, and highly orthogonal binding specificities. Thus crisscross growth provides a route for prototyping and scalable production of structures integrating thousands of unique components (that is, origami slats) that each is sophisticated and molecularly precise.
(© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

RNA, Guide, Kinetoplastida genetics, CRISPR-Cas Systems genetics, and RNA

The ability to control protein expression at both the transcriptional and post-transcriptional levels is instrumental for the cell to integrate multiple molecular signals and then reach high operational sophistication. Although challenging, fully artificial regulations at different levels are required for boosting systems and synthetic biology. Here, we report the development of a novel framework to regulate translation by repurposing the CRISPR-Cas13 immune system, which uses an RNA-guided ribonuclease. By exploiting a cell-free expression system for prototyping gene regulatory structures, our results demonstrate that CRISPR-dCas13a ribonucleoproteins (d means catalytically dead) can be programmed to repress or activate translation initiation. The performance assessment of the engineered systems also revealed guide RNA design principles. Moreover, we show that the system can work in vivo . This development complements the ability to regulate transcription with other CRISPR-Cas systems and offers potential applications.

Microactuators can autonomously convert external energy into specific mechanical motions. With the feature sizes varying from the micrometer to millimeter scale, microactuators offer many operation and control possibilities for miniaturized devices. In recent years, advanced microfluidic techniques have revolutionized the fabrication, actuation, and functionalization of microactuators. Microfluidics can not only facilitate fabrication with continuously changing materials but also deliver various signals to stimulate the microactuators as desired, and consequently improve microfluidic chips with multiple functions. Herein, this cross-field that systematically correlates microactuator properties and microfluidic functions is comprehensively reviewed. The fabrication strategies are classified into two types according to the flow state of the microfluids: stop-flow and continuous-flow prototyping. The working mechanism of microactuators in microfluidic chips is discussed in detail. Finally, the applications of microactuator-enriched functional chips, which include tunable imaging devices, micromanipulation tools, micromotors, and microsensors, are summarized. The existing challenges and future perspectives are also discussed. It is believed that with the rapid progress of this cutting-edge field, intelligent microsystems may realize high-throughput manipulation, characterization, and analysis of tiny objects and find broad applications in various fields, such as tissue engineering, micro/nanorobotics, and analytical devices.
(© 2023 Wiley-VCH GmbH.)

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

Background: Because of the association of textured breast implants with breast implant-associated anaplastic large cell lymphoma, anatomically shaped breast implants, which rely on a textured surface to maintain rotational stability, have been recalled from the market. The dearth of anatomically shaped implants on the market reflects a need for novel breast implant technology, which has been traditionally developed by commercial breast implant manufacturers due to the complexities of implant manufacturing. To increase the accessibility of preclinical breast implant research, miniature breast implants made from polydimethylsiloxane were designed and fabricated for high throughput and low-cost prototyping and in vivo testing of both smooth and textured implants in a laboratory setting.
Methods: Two-piece negative molds measuring 2 × 1 cm were constructed in Fusion360 and 3D printed in Polysmooth filament. Textured molds were painted with a mixture of an epoxy and fine sugar or granular salt to create textured surfaces, while molds for smooth implants were smoothed using ethanol spray. Molds were injected with polydimethylsiloxane and cured for 12 hours at 37°C. The surface topography of laboratory-made implants and commercial textured and smooth implant shells was analyzed using scanning electron microscopy and implants were evaluated in vivo in an immunocompetent rodent model.
Results: Implants retained the original dome shape of the 3D-printed molds. Qualitative assessment of scanning electron microscopy images demonstrated similar surface topography between laboratory-made and commercial smooth and textured implants. There was no statistical difference in the diameter or density of the surface indentations of the Allergan's textured implant compared with laboratory-made textured implants (P > 0.05). Finally, the surface topography and thickness of laboratory-made implant capsules were similar to previously published data using industry made miniature silicone devices implanted in rats.
Conclusions: This study demonstrates a low-cost, highly customizable approach to fabricate miniature smooth and textured breast implant prototypes for in vivo studies. The accessibility of this implant fabrication strategy allows nonindustry investigators to develop novel implant designs more rapidly for preclinical investigation.
Competing Interests: Conflicts of interest and sources of funding: none declared.
(Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Vital Signs and Wearable Electronic Devices

Embedded systems have become a key technology for the evolution of medical devices. However, the regulatory requirements that must be met make designing and developing these devices challenging. As a result, many start-ups attempting to develop medical devices fail. Therefore, this article presents a methodology to design and develop embedded medical devices while minimising the economic investment during the technical risk stages and encouraging customer feedback. The proposed methodology is based on the execution of three stages: Development Feasibility, Incremental and Iterative Prototyping, and Medical Product Consolidation. All this is completed in compliance with the applicable regulations. The methodology mentioned above is validated through practical use cases in which the development of a wearable device for monitoring vital signs is the most relevant. The presented use cases sustain the proposed methodology, for the devices were successfully CE marked. Moreover, ISO 13485 certification is obtained by following the proposed procedures.

Hard carbons (HCs) are extensively investigated as the potential anodes for commercialization of sodium-ion batteries (SIBs). However, the practical deployment of HC anode suffers from the retarded Na + diffusion at the high-rate or low-temperature operation scenarios. Herein, a multiscale modification strategy by tuning HC microstructure on the particle level as well as replenishing extra Na + reservoir for the electrode through a homogeneous presodiation therapy is presented. Consequently, the coulombic efficiency of HC anode can be precisely controlled till the close-to-unit value. Detailed kinetics analysis observes that the Na + diffusivity can be drastically enhanced by two orders of magnitude at the low potential region (< 0.1 V vs. Na + /Na), which accelerates the rate-limiting step. As pairing the presodiated HC anode (≈5.0 ± 0.2 mg cm -2 ) with the NaVPO 4 F cathode (≈10.3 mg cm -2 ) in the 200 mAh pouch cell, the optimal balance of the cyclability (83% over 1000 cycles), low-temperature behavior till -40 °C as well as the maximized power output of 1500 W kg -1 can be simultaneously achieved. This synergistic modification strategy opens a new avenue to exploit the reversible, ultrafast Na + storage kinetics of HC anodes, which thus constitutes a quantum leap forward toward high-rate SIB prototyping.
(© 2023 Wiley-VCH GmbH.)

Recombinant Proteins, Biocompatible Materials, Bacterial Proteins, Chromatography methods, and Nanostructures chemistry

Background: Protein nanostructures produced through the self-assembly of individual subunits are attractive scaffolds to attach and position functional molecules for applications in biomaterials, metabolic engineering, tissue engineering, and a plethora of nanomaterials. However, the assembly of multicomponent protein nanomaterials is generally a laborious process that requires each protein component to be separately expressed and purified prior to assembly. Moreover, excess components not incorporated into the final assembly must be removed from the solution and thereby necessitate additional processing steps.
Results: We developed an efficient approach to purify functionalized protein nanostructures directly from bacterial lysates through a type of multimodal chromatography (MMC) that combines size-exclusion, hydrophilic interaction, and ion exchange to separate recombinant protein assemblies from excess free subunits and bacterial proteins. We employed the ultrastable filamentous protein gamma-prefoldin as a material scaffold that can be functionalized with a variety of protein domains through SpyTag/SpyCatcher conjugation chemistry. The purification of recombinant gamma-prefoldin filaments from bacterial lysates using MMC was tested across a wide range of salt concentrations and pH, demonstrating that the MMC resin is robust, however the optimal choice of salt species, salt concentration, and pH is likely dependent on the protein nanostructure to be purified. In addition, we show that pre-processing of the samples with tangential flow filtration to remove nucleotides and metabolites improves resin capacity, and that post-processing with Triton X-114 phase partitioning is useful to remove lipids and any remaining lipid-associated protein. Subsequently, functionalized protein filaments were purified from bacterial lysates using MMC and shown to be free of unincorporated subunits. The assembly and purification of protein filaments with varying amounts of functionalization was confirmed using polyacrylamide gel electrophoresis, Förster resonance energy transfer, and transmission electron microscopy. Finally, we compared our MMC workflow to anion exchange chromatography with the purification of encapsulin nanocompartments containing a fluorescent protein as a cargo, demonstrating the versatility of the protocol and that the purity of the assembly is comparable to more traditional procedures.
Conclusions: We envision that the use of MMC will increase the throughput of protein nanostructure prototyping as well as enable the upscaling of the bioproduction of protein nanodevices.
(© 2023. The Author(s).)

Humans, Animals, Dogs, Femur surgery, Patella surgery, Cartilage surgery, Arthroplasty, Replacement, Knee adverse effects, and Patellar Dislocation surgery

Patellar luxation with condylar defect is a challenging situation for reconstruction in humans. Patella reluxation, cartilage damage and pain are the most common complications. This study aims to present a new patient specific method of overformed implant design and clinical implantation that prevents luxation of patella without damaging the cartilage in a dog. Design processes are Computer Tomography, Computer Assisted Design, rapid prototyping of the bone replica, creation of the implant with surgeon's haptic knowledge on the bone replica, 3D printing of the implant and clinical application. The implant was fully seated on the bone. Patella reluxation or implant-related bone problem was not observed 80 days after the operation. However, before the implant application, there were soft tissue problems due to previous surgeries. Three-point bending test and finite element analysis were performed to determine the biomechanical safety of the implant. The stress acting on the implant was below the biomechanical limits of the implant. More cases with long-term follow-up are needed to confirm the success of this method in patellar luxation. Compared with trochlear sulcoplasty and total knee replacement, there was no cartilage damage done by surgeons with this method, and the implant keeps the patella functionally in sulcus. This is a promising multidisciplinary method that can be applied to any part of the bone and can solve some orthopaedic problems with surgeon's haptic knowledge.
(© 2023. The Author(s).)

Cell-Free System metabolism, Multigene Family, Streptomyces genetics, and Biological Products metabolism

Streptomyces bacteria are a major microbial source of natural products, which are encoded within so-called biosynthetic gene clusters (BGCs). This highlight discusses the emergence of native Streptomyce s cell-free systems as a new tool to accelerate the study of the fundamental chemistry and biology of natural product biosynthesis from these bacteria. Cell-free systems provide a prototyping platform to study plug-and-play reactions in microscale reactions. So far, Streptomyce s cell-free systems have been used to rapidly characterise gene expression regulation, access secondary metabolite biosynthetic enzymes, and catalyse cell-free transcription, translation, and biosynthesis of example natural products. With further progress, we anticipate the development of more complex systems to complement existing experimental tools for the discovery and engineering of natural product biosynthesis from Streptomyces and related high G + C (%) bacteria.

An abnormality in neural connectivity is linked to autism spectrum disorder (ASD). There is no way to test the concept of neural connectivity empirically. According to recent network theory and time series analysis findings, electroencephalography (EEG) can assess neural network architecture, a sign of activity in the brain. This systematic review aims to evaluate functional connectivity and spectral power using EEG signals. EEG records the brain activity of an individual by displaying wavy lines that depict brain cells' communication through electrical impulses. EEG can diagnose various brain disorders, including epilepsy and related seizure illness, brain dysfunction, tumors, and damage. We found 21 studies using two of the most common EEG analysis methods: functional connectivity and spectral power. ASD and non-ASD individuals were found to differ significantly in all selected papers. Due to high heterogeneity in the outcomes, generalizations cannot be drawn, and no single method is currently beneficial as a diagnostic tool. For ASD subtype delineation, the lack of research prevented the evaluation of these techniques as diagnostic tools. These findings confirm the presence of abnormalities in the EEG in ASD, but they are insufficient to diagnose. Our study suggests that EEG is useful in diagnosing ASD by evaluating entropy in the brain. Researchers may be able to develop new diagnostic methods for ASD which focuses on particular stimuli and brainwaves if they conduct more extensive studies with higher numbers and more rigorous study designs.
Competing Interests: The authors report no conflicts of interest in this work.
(© 2023 Bogéa Ribeiro and da Silva Filho.)

Composites based on poly(3,4-ethylenedioxythiophene): poly(styrene sulfonate) (PEDOT:PSS)-graphene oxide (GO) are increasingly considered for sensing applications. In this work we aim at patterning and prototyping microscale geometries of PEDOT:PSS: GO composites for the modification of commercially available electrochemical sensors. Here, we demonstrate the laser-induced forward transfer of PEDOT:PSS: GO composites, a remarkably simple procedure that allows for the fast and clean transfer of materials with high resolution for a wide range of laser fluences (450-750 mJ/cm 2 ). We show that it is possible to transfer PEDOT:PSS: GO composites at different ratios (i.e., 25:75 %wt and 50:50 %wt) onto flexible screen-printed electrodes. Furthermore, when testing the functionality of the PEDOT:PSS: GO modified electrodes via LIFT, we could see that both the PEDOT:PSS: GO ratio as well as the addition of an intermediate release layer in the LIFT process plays an important role in the electrochemical response. In particular, the ratio of the oxidation peak current to the reduction peak current is almost twice as high for the sensor with a 50:50 %et PEDOT:PSS: GO pixel. This direct transfer methodology provides a path forward for the prototyping and production of polymer: graphene oxide composite based devices.

Humans, Fractals, Skin, Keratinocytes metabolism, Electromagnetic Phenomena, and Malassezia

Malassezia spp. are dimorphic, lipophilic fungi that are part of the normal human cutaneous commensal microbiome. However, under adverse conditions, these fungi can be involved in various cutaneous diseases. In this study, we analysed the effect of ultra-weak fractal electromagnetic (uwf-EMF) field exposure (12.6 nT covering 0.5 to 20 kHz) on the growth dynamics and invasiveness of M. furfur . The ability to modulate inflammation and innate immunity in normal human keratinocytes was also investigated. Using a microbiological assay, it was possible to demonstrate that, under the influence of uwf-EMF, the invasiveness of M. furfur was drastically reduced (d = 2.456, p < 0.001), while at the same time, its growth dynamic after 72 h having been in contact with HaCaT cells both without (d = 0.211, p = 0.390) and with (d = 0.118, p = 0.438) uwf-EM exposure, were hardly affected. Real-time PCR analysis demonstrated that a uwf-EMF exposure is able to modulate human-β-defensin-2 (hBD-2) in treated keratinocytes and at the same time reduce the expression of proinflammatory cytokines in human keratinocytes. The findings suggest that the underlying principle of action is hormetic in nature and that this method might be an adjunctive therapeutic tool to modulate the inflammatory properties of Malassezia in related cutaneous diseases. The underlying principle of action becomes understandable by means of quantum electrodynamics (QED). Given that living systems consist mainly of water and within the framework of QED, this water, as a biphasic system, provides the basis for electromagnetic coupling. The oscillatory properties of water dipoles modulated by weak electromagnetic stimuli not only affect biochemical processes, but also pave the way for a more general understanding of the observed nonthermal effects in biota.

Additive Manufacturing (AM) techniques have recently attracted the attention of scientists for the development of prototypes with complex or particular geometry in a fast and cheap way. Among the different AM processes, the Fused Deposition Modelling process (FDM) offers several advantages in terms of costs, implementation features and design freedom. Recently, it has been adopted to realise auxetic structures, which are characterised by negative Poisson ratio, enhanced mechanical properties, and a higher compression resistance than conventional structures. This review outlines the use of AM processes, in particular FDM, to design and obtain auxetic structures, with the final aim to exploit their applications in different fields. The first part of this work presents a brief classification of auxetic structures and materials. Subsequently, a summary of additive manufacturing processes is presented, focusing on the use of FDM and its limitations. Finally, the studies on the use of additive manufacturing to produce auxetic structures are shown, evidencing the potential of the concurrent combination of a fast prototyping technique such as FDM and the characteristics of polymer- and/or composite-based auxetic structures. Indeed, this new technological field opens the possibility of realising novel structures with integrated smart behaviour, multifunctional properties, compression resistance, and a tailored microstructure and shape.

Escherichia coli genetics, Escherichia coli metabolism, Cell-Free System metabolism, Plant Extracts metabolism, Protein Biosynthesis, and Proteomics

Cell-free systems derived from crude cell extracts have developed into tools for gene expression, with applications in prototyping, biosensing, and protein production. Key to the development of these systems is optimization of cell extract preparation methods. However, the applied nature of these optimizations often limits investigation into the complex nature of the extracts themselves, which contain thousands of proteins and reaction networks with hundreds of metabolites. Here, we sought to uncover the black box of proteins and metabolites in Escherichia coli cell-free reactions based on different extract preparation methods. We assess changes in transcription and translation activity from σ 70 promoters in extracts prepared with acetate or glutamate buffer and the common post-lysis processing steps of a runoff incubation and dialysis. We then utilize proteomic and metabolomic analyses to uncover potential mechanisms behind these changes in gene expression, highlighting the impact of cold shock-like proteins and the role of buffer composition.

As a result of the developments in additive manufacturing (AM) technology, 3D printing is transforming from a method used only in rapid prototyping to a technique used to produce large-scale equipment. This study presents the fabrication and experimental studies of a 3D-printed strain sensor that can be used directly in soft applications. Photopolymer-based conductive and flexible ultraviolet (UV) resin materials are used in the fabrication of the sensor. A Stereolithography (SLA)-based printer is preferred for 3D fabrication. The bottom base of the sensor, which consists of two parts, is produced from flexible UV resin, while the channels that should be conductive are produced from conductive UV resin. In total, a strain sensor with a thickness of 2 mm was produced. Experimental studies were carried out under loading and unloading conditions to observe the hysteresis effect of the sensor. The results showed a close linear relationship between the strain sensor and the measured resistance value. In addition, tensile test specimens were produced to observe the behavior of conductive and non-conductive materials. The tensile strength values obtained from the test results will provide information about the sensor placement. In addition, the flexible structure of the strain sensor will ensure its usability in many soft applications.

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

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

Electrons, Quantum Theory, and Software

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

Tissue Engineering, Perfusion, Lab-On-A-Chip Devices, and Volatile Organic Compounds

Creating vascularised cellular environments in vitro is a current challenge in tissue engineering and a bottleneck towards developing functional stem cell-derived microtissues for regenerative medicine and basic investigations. Here we have developed a new workflow to manufacture vasculature on chip (VoC) systems efficiently, quickly, and inexpensively. We have employed 3D printing for fast-prototyping of bespoke VoC and coupled them with a refined organotypic culture system (OVAA) to grow patent capillaries in vitro using tissue-specific endothelial and stromal cells. Furthermore, we have designed and implemented a pocket-size flow driver to establish physiologic perfusive flow throughout our VoC-OVAA with minimal medium use and waste. Using our platform, we have created vascularised microtissues and perfused them at physiologic flow rates for extended time (>2 weeks) observing flow-dependent vascular remodelling. Overall, we present for the first time a scalable and customisable system to grow vascularised and perfusable microtissues, a key initial step to grow mature and functional tissues in vitro . We envision that this technology will empower fast prototyping and validation of increasingly biomimetic in vitro systems, including interconnected multi-tissue systems.

Recent years have seen remarkable progress in our scientific understanding of early childhood social, emotional, and cognitive development, as well as our capacity to widely disseminate health information by using digital technologies. Together, these scientific and technological advances offer exciting opportunities to deliver high-quality information about early childhood development (ECD) to parents and families globally, which may ultimately lead to greater knowledge and confidence among parents and better outcomes among children (particularly in lower- and middle-income countries). With these potential benefits in mind, we set out to design, develop, implement, and evaluate a new parenting app-Thrive by Five-that will be available in 30 countries. The app will provide caregivers and families with evidence-based and culturally appropriate information about ECD, accompanied by sets of collective actions that go beyond mere tips for parenting practices. Herein, we describe this ongoing global project and discuss the components of our scientific framework for developing and prototyping the app's content. Specifically, we describe (1) 5 domains that are used to organize the content and goals of the app's information and associated practices; (2) 5 neurobiological systems that are relevant to ECD and can be behaviorally targeted to potentially influence social, emotional, and cognitive development; (3) our anthropological and cultural framework for learning about local contexts and appreciating decolonization perspectives; and (4) our approach to tailoring the app's content to local contexts, which involves collaboration with in-country partner organizations and local and international subject matter experts in ECD, education, medicine, psychology, and anthropology, among others. Finally, we provide examples of the content that was incorporated in Thrive by Five when it launched globally.
(©Jacob J Crouse, Haley M LaMonica, Yun Ju Christine Song, Kelsie A Boulton, Cathrin Rohleder, Marilena M DeMayo, Chloe E Wilson, Victoria Loblay, Gabrielle Hindmarsh, Tina Stratigos, Michael Krausz, Nathanael Foo, Melissa Teo, Andrew Hunter, Adam J Guastella, Richard B Banati, Jakelin Troy, Ian B Hickie. Originally published in JMIR Pediatrics and Parenting (https://pediatrics.jmir.org), 13.02.2023.)

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

Employees who work long hours frequently complain of muscle fatigue caused by prolonged sitting. As a result, products that assist them when resting in a chair in a reclining position, in order to relieve fatigue and improve comfort are required. To ensure that the new product works as intended, a usability test based on prototyping must be developed. The research process was divided into three stages: firstly, the development of the perception assessment questionnaire; secondly, a validated factor analysis (CFA) was conducted on the perception assessment data of 26 subjects and the measurement model was fitted to verify the reliability and validity of the questionnaire; finally, the sEMG technique was used to verify the comfort level of 21 subjects. Based on usability experiments and an exploration of human factor relationships, this study develops a prototype testing model, which focuses on the comfort perception of body parts, as a means of promoting innovation in the design and manufacturing industry.
Competing Interests: The authors declare no competing interests.
(© 2023 The Authors.)

Tissue Engineering, Acoustics, Hydrogels chemistry, Sound, and Holography

Acoustic waves exert forces when they interact with matter. Shaping ultrasound fields precisely in 3D thus allows control over the force landscape and should permit particulates to fall into place to potentially form whole 3D objects in "one shot." This is promising for rapid prototyping, most notably biofabrication, since conventional methods are typically slow and apply mechanical or chemical stress on biological cells. Here, we realize the generation of compact holographic ultrasound fields and demonstrate the one-step assembly of matter using acoustic forces. We combine multiple holographic fields that drive the contactless assembly of solid microparticles, hydrogel beads, and biological cells inside standard labware. The structures can be fixed via gelation of the surrounding medium. In contrast to previous work, this approach handles matter with positive acoustic contrast and does not require opposing waves, supporting surfaces or scaffolds. We envision promising applications of 3D holographic ultrasound fields in tissue engineering and additive manufacturing.

Graph generative models have recently emerged as an interesting approach to construct molecular structures atom-by-atom or fragment-by-fragment. In this study, we adopt the fragment-based strategy and decompose each input molecule into a set of small chemical fragments. In drug discovery, a few drug molecules are designed by replacing certain chemical substituents with their bioisosteres or alternative chemical moieties. This inspires us to group decomposed fragments into different fragment clusters according to their local structural environment around bond-breaking positions. In this way, an input structure can be transformed into an equivalent three-layer graph, in which individual atoms, decomposed fragments, or obtained fragment clusters act as graph nodes at each corresponding layer. We further implement a prototype model, named multi-resolution graph variational autoencoder (MRGVAE), to learn embeddings of constituted nodes at each layer in a fine-to-coarse order. Our decoder adopts a similar but conversely hierarchical structure. It first predicts the next possible fragment cluster, then samples an exact fragment structure out of the determined fragment cluster, and sequentially attaches it to the preceding chemical moiety. Our proposed approach demonstrates comparatively good performance in molecular evaluation metrics compared with several other graph-based molecular generative models. The introduction of the additional fragment cluster graph layer will hopefully increase the odds of assembling new chemical moieties absent in the original training set and enhance their structural diversity. We hope that our prototyping work will inspire more creative research to explore the possibility of incorporating different kinds of chemical domain knowledge into a similar multi-resolution neural network architecture.
(© 2023 Wiley-VCH GmbH.)

Humans, Drug Delivery Systems, Pharmaceutical Preparations, Printing, Three-Dimensional, Technology, Pharmaceutical methods, and Artificial Intelligence

There has been a tremendous increase in the investigations of three-dimensional (3D) printing for biomedical and pharmaceutical applications, and drug delivery in particular, ever since the US FDA approved the first 3D printed medicine, SPRITAM® (levetiracetam) in 2015. Three-dimensional printing, also known as additive manufacturing, involves various manufacturing techniques like fused-deposition modeling, 3D inkjet, stereolithography, direct powder extrusion, and selective laser sintering, among other 3D printing techniques, which are based on the digitally controlled layer-by-layer deposition of materials to form various geometries of printlets. In contrast to conventional manufacturing methods, 3D printing technologies provide the unique and important opportunity for the fabrication of personalized dosage forms, which is an important aspect in addressing diverse patient medical needs. There is however the need to speed up the use of 3D printing in the biopharmaceutical industry and clinical settings, and this can be made possible through the integration of modern technologies like artificial intelligence, machine learning, and Internet of Things, into additive manufacturing. This will lead to less human involvement and expertise, independent, streamlined, and intelligent production of personalized medicines. Four-dimensional (4D) printing is another important additive manufacturing technique similar to 3D printing, but adds a 4th dimension defined as time, to the printing. This paper aims to give a detailed review of the applications and principles of operation of various 3D printing technologies in drug delivery, and the materials used in 3D printing, and highlight the challenges and opportunities of additive manufacturing, while introducing the concept of 4D printing and its pharmaceutical applications.
(© 2023. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

This work investigated the feasibility of using a miniaturised non-standard tensile specimen to predict the post-necking behaviour of the materials manufactured via a rapid alloy prototyping (RAP) approach. The experimental work focused on the determination of the Lankford coefficients (r-value) of dual-phase 800 (DP800) steel and the digital image correlation (DIC) for some cases, which were used to help calibrate the damage model parameters of DP800 steel. The three-dimensional numerical simulations focused on the influence of the size effect (aspect ratio, AR) on the post-necking behaviour, such as the strain/stress/triaxiality evolutions, fracture angles, and necking mode transitions. The modelling showed that although a good correlation can be found between the predicted and experimentally observed ultimate tensile strength (UTS) and total elongation. The standard tensile specimen with a gauge length of 80 mm exhibited a fracture angle of ∼55°, whereas the smaller miniaturised non-standard specimens with low ARs exhibited fractures perpendicular to the loading direction. This shows that care must be taken when comparing the post-necking behaviour of small-scale tensile tests, such as those completed as a part of a RAP approach, to the post-necking behaviours of standard full-size test specimens. However, the modelling work showed that this behaviour is well represented, demonstrating a transition between the fracture angles of the samples between 2.5 and 5. This provides more confidence in understanding the post-necking behaviour of small-scale tensile tests.

Background. The complexity of decision science models may prevent their use to assist in decision making. User-centered design (UCD) principles provide an opportunity to engage end users in model development and refinement, potentially reducing complexity and increasing model utilization in a practical setting. We report our experiences with UCD to develop a modeling tool for cancer control planners evaluating cancer survivorship interventions. Design. Using UCD principles (described in the article), we developed a dynamic cohort model of cancer survivorship for individuals with female breast, colorectal, lung, and prostate cancer over 10 y. Parameters were obtained from the National Program of Cancer Registries and peer-reviewed literature, with model outcomes captured in quality-adjusted life-years and net monetary benefit. Prototyping and iteration were conducted with structured focus groups involving state cancer control planners and staff from the Centers for Disease Control and Prevention and the American Public Health Association. Results. Initial feedback highlighted model complexity and unclear purpose as barriers to end user uptake. Revisions addressed complexity by simplifying model input requirements, providing clear examples of input types, and reducing complex language. Wording was added to the results page to explain the interpretation of results. After these updates, feedback demonstrated that end users more clearly understood how to use and apply the model for cancer survivorship resource allocation tasks. Conclusions. A UCD approach identified challenges faced by end users in integrating a decision aid into their workflow. This approach created collaboration between modelers and end users, tailoring revisions to meet the needs of the users. Future models developed for individuals without a decision science background could leverage UCD to ensure the model meets the needs of the intended audience.
Highlights: Model complexity and unclear purpose are 2 barriers that prevent lay users from integrating decision science tools into their workflow.Modelers could integrate the user-centered design framework when developing a model for lay users to reduce complexity and ensure the model meets the needs of the users.
Competing Interests: JAR is currently employed at Pfizer but was an associate professor at Fred Hutchinson Cancer Center when he made his contributions to this article. The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Financial support to the Fred Hutchinson Cancer Center for this study was provided by a subcontract from the American Public Health Association, which received support from the Centers for Disease Control and Prevention (CDC) through cooperative agreement 6NU38OT000294-01-02. The findings and conclusions in this article are those of the authors and do not necessarily represent the official position of the CDC. The following authors are employed by the CDC: Lisa Richardson, MD, MPH; Sun Hee Rim, PhD, MPH; Cheryll C. Thomas, MSPH; and Julie S. Townsend, MS. Use of trade names is for identification only and does not imply endorsement by the US Department of Health and Human Services.
(© The Author(s) 2023.)

Objectives: A videofluoroscopic swallowing study (VFSS) is conducted to detect aspiration. However, aspiration occurs within a short time and is difficult to detect. If deep learning can detect aspirations with high accuracy, clinicians can focus on the diagnosis of the detected aspirations. Whether VFSS aspirations can be classified using rapid-prototyping deep-learning tools was studied.
Methods: VFSS videos were separated into individual image frames. A region of interest was defined on the pharynx. Three convolutional neural networks (CNNs), namely a Simple-Layer CNN, Multiple-Layer CNN, and Modified LeNet, were designed for the classification. The performance results of the CNNs were compared in terms of the areas under their receiver-operating characteristic curves (AUCs).
Results: A total of 18,333 images obtained through data augmentation were selected for the evaluation. The different CNNs yielded sensitivities of 78.8%-87.6%, specificities of 91.9%-98.1%, and overall accuracies of 85.8%-91.7%. The AUC of 0.974 obtained for the Simple-Layer CNN and Modified LeNet was significantly higher than that obtained for the Multiple-Layer CNN (AUC of 0.936) (p < 0.001).
Conclusions: The results of this study show that deep learning has potential for detecting aspiration with high accuracy.
(© 2023. The Author(s) under exclusive licence to Japanese Society for Oral and Maxillofacial Radiology.)

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

The use of three-dimensional (3-D) technology in upper extremity surgery has the potential to revolutionize the way that hand and upper limb procedures are planned and performed. 3-D technology can assist in the diagnosis and treatment of conditions, allowing virtual preoperative planning and surgical templating. 3-D printing can allow the production of patient-specific jigs, instruments and implants, allowing surgeons to plan and perform complex procedures with greater precision and accuracy. Previously, cost has been a barrier to the use of 3-D technology, which is now falling rapidly. This review article will discuss the current status of 3-D technology and printing, including its applications, ethics and challenges in hand and upper limb surgery. We have provided case examples to outline how clinicians can incorporate 3-D technology in their clinical practice for congenital deformities, management of acute fracture and malunion and arthroplasty.

Three-dimensional printing for medical applications in surgery of the upper extremity has gained in popularity as reflected by the increasing number of publications. This systematic review aims to provide an overview of the clinical use of 3D printing in upper extremity surgery.
Methods: We searched the databases PubMed and Web of Science for clinical studies that described clinical application of 3D printing for upper extremity surgery including trauma and malformations. We evaluated study characteristics, clinical entity, type of clinical application, concerned anatomical structures, reported outcomes, and evidence level.
Results: We finally included 51 publications with a total of 355 patients, of which 12 were clinical studies (evidence level II/III) and 39 case series (evidence level IV/V). The types of clinical applications were for intraoperative templates (33% of a total of 51 studies), body implants (29%), preoperative planning (27%), prostheses (15%), and orthoses (1%). Over two third of studies were linked to trauma-related injuries (67%).
Conclusion: The clinical application of 3D printing in upper extremity surgery offers great potential for personalized approaches to aid in individualized perioperative management, improvement of function, and ultimately help to benefit certain aspects in the quality of life.
Competing Interests: The authors declare no conflict of interest.

Over the last few years, biopolymers have attracted great interest in tissue engineering and regenerative medicine due to the great diversity of their chemical, mechanical, and physical properties for the fabrication of 3D scaffolds. This review is devoted to recent advances in synthetic and natural polymeric 3D scaffolds for bone tissue engineering (BTE) and regenerative therapies. The review comprehensively discusses the implications of biological macromolecules, structure, and composition of polymeric scaffolds used in BTE. Various approaches to fabricating 3D BTE scaffolds are discussed, including solvent casting and particle leaching, freeze-drying, thermally induced phase separation, gas foaming, electrospinning, and sol-gel techniques. Rapid prototyping technologies such as stereolithography, fused deposition modeling, selective laser sintering, and 3D bioprinting are also covered. The immunomodulatory roles of polymeric scaffolds utilized for BTE applications are discussed. In addition, the features and challenges of 3D polymer scaffolds fabricated using advanced additive manufacturing technologies (rapid prototyping) are addressed and compared to conventional subtractive manufacturing techniques. Finally, the challenges of applying scaffold-based BTE treatments in practice are discussed in-depth.

The on-surface synthesis of nano-graphenes has led the charge in prototyping structures with perspectives beyond silicon-based technology. Following reports of open-shell systems in graphene-nanoribbons (GNRs), a flurry of research activity was directed at investigating their magnetic properties with a keen eye for spintronic applications. Although the synthesis of nano-graphenes is usually carried out on Au(111), the substrate is difficult to use for electronic decoupling and spin-polarized measurements. Using a binary alloy Cu 3 Au(111), we show possibilities for gold-like on-surface synthesis compatible with spin polarization and electronic decoupling known from copper. We prepare copper oxide layers, demonstrate the synthesis of GNRs, and grow thermally stable magnetic Co islands. We functionalize the tip of a scanning tunneling microscope with carbon-monoxide, nickelocene, or attach Co clusters for high-resolution imaging, magnetic sensing, or spin-polarized measurements. This versatile platform will be a valuable tool in the advanced study of magnetic nano-graphenes.
Competing Interests: There are no conflicts to declare.
(This journal is © The Royal Society of Chemistry.)

Mice, Animals, Electrodes, Prostheses and Implants, Brain, Sulfhydryl Compounds chemistry, and Nervous System

Off-stoichiometry thiol-ene-epoxy (OSTE+) thermosets show low permeability to gases and little absorption of dissolved molecules, allow direct low-temperature dry bonding without surface treatments, have a low Young's modulus, and can be manufactured via UV polymerisation. For these reasons, OSTE+ thermosets have recently gained attention for the rapid prototyping of microfluidic chips. Moreover, their compatibility with standard clean-room processes and outstanding mechanical properties make OSTE+ an excellent candidate as a novel material for neural implants. Here we exploit OSTE+ to manufacture a conformable multilayer micro-electrocorticography array with 16 platinum electrodes coated with platinum black. The mechanical properties allow conformability to curved surfaces such as the brain. The low permeability and strong adhesion between layers improve the stability of the device. Acute experiments in mice show the multimodal capacity of the array to record and stimulate the neural tissue by smoothly conforming to the mouse cortex. Devices are not cytotoxic, and immunohistochemistry stainings reveal only modest foreign body reaction after two and six weeks of chronic implantation. This work introduces OSTE+ as a promising material for implantable neural interfaces.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Diego Ghezzi reports financial support was provided by Medtronic plc.
(Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Nanogels

Layered double hydroxides (LDHs) offer unique source of inspiration for design of bone mimetic biomaterials due to their superior mechanical properties, drug delivery capability and regulation cellular behaviors, particularly by divalent metal cations in their structure. Three-dimensional (3D) bioprinting of LDHs holds great promise as a novel strategy thanks to highly tunable physiochemical properties and shear-thinning ability of LDHs, which allow shape fidelity after deposition. Herein, we introduce a straightforward strategy for extrusion bioprinting of cell laden nanocomposite hydrogel bioink of gelatin methacryloyl (GelMA) biopolymer and LDHs nanoparticles. First, we synthesized LDHs by co-precipitation process and systematically examined the effect of LDHs addition on printing parameters such as printing pressure, extrusion rate, printing speed, and finally bioink printability in creating grid-like constructs. The developed hydrogel bioinks provided precise control over extrudability, extrusion uniformity, and structural integrity after deposition. Based on the printability and rheological analysis, the printability could be altered by controlling the concentration of LDHs, and printability was found to be ideal with the addition of 3 wt % LDHs. The addition of LDHs resulted in remarkably enhanced compressive strength from 652 kPa (G-LDH0) to 1168 kPa (G-LDH3). It was shown that the printed nanocomposite hydrogel scaffolds were able to support encapsulated osteoblast survival, spreading, and proliferation in the absence of any osteoinductive factors taking advantage of LDHs. In addition, cells encapsulated in G-LDH3 had a larger cell spreading area and higher cell aspect ratio than those encapsulated in G-LDH0. Altogether, the results demonstrated that the developed GelMA/LDHs nanocomposite hydrogel bioink revealed a high potential for extrusion bioprinting with high structural fidelity to fabricate implantable 3D hydrogel constructs for repair of bone defects.
(© 2022 Wiley Periodicals LLC.)

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

Polyacrylonitrile (PAN) represents the most widely used precursor for carbon fibers and carbon materials. Carbon materials stand out with their high mechanical performance, but they also show excellent electrical conductivity and high surface area. These properties render carbon materials suitable as electrode material for fuel cells, batteries, and supercapacitors. However, PAN has to be processed from solution before being thermally converted to carbon, limiting its final format to fibers, films, and non-wovens. Here, a PAN-copolymer with an intrinsic plasticizer is presented to reduce the melting temperature and avoid undesired entering of the thermal carbonization regime. This plasticizer enables melt extrusion-based additive manufacturing (EAM). The plasticizer in the PAN-copolymer can be switched to increase the melting temperature after processing, allowing the 3D-melt-printed workpiece to be thermally carbonized after EAM. Melt-processing of the PAN copolymer extends the freedom-in-design of carbon materials to mold-free rapid prototyping, in the absence of solvents, which enables more economic and sustainable manufacturing processes. As an example for the capability of this material system, open meshed carbon electrodes are printed for supercapacitors that are metal- and binder-free with an optimized thickness of 1.5 mm and a capacitance of up to 387 mF cm -2 .
(© 2022 The Authors. Advanced Materials published by Wiley-VCH GmbH.)

Humans, Australia, Bibliometrics, China, Printing, Three-Dimensional, and Scoliosis

Purpose: Although numerous publications on three-dimensional printing (3DP) in spine surgery have been published, bibliometric analysis studies are scarce. Thus, this study aimed to present a bibliometric analysis of the status, hot spots, and frontiers of 3DP in spine surgery and associated research disciplines.
Methods: All publications relating to the utilization of 3DP in spine surgery from 1999 to May 9, 2022, were retrieved from the Web of Science. The bibliometric analysis was performed using CiteSpace software, and information on the country, institution, author, journal, and keywords for each publication was collected.
Results: A total of 270 articles were identified. From 2016 onward, a significant increase in publications on spinal surgery was observed. China was the most productive and influential country (98 publications) and H-index (22), followed by the USA and Australia. The most productive institution was Capital Medical University (9 publications). P. S. D'urso (8 publications, 46 citations) and R. J. Mobbs (8 publications, 39 citations) were the most prolific authors. European Spine Journal contributed the highest number of publications. The eight main clusters were: "rapid prototyping" #0, "3D printed" #1, "spine fusion" #2, "scoliosis" #3, "spine surgery" #4, "patient-specific" #5, "nervous system" #6, and "neuronavigation" #7. The strongest keyword bursts in 3DP in spine surgery were "fixation," "drill template," "instrumentation," "fusion," "complication," and "atlantoaxial instability."
Conclusion: This analysis provides information on research trends and frontiers in the application of 3DP in spine surgery, as well as research and collaboration partners, institutions, and countries.
(© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Radionuclide Imaging, Microscopy, Fluorescence methods, Spectrometry, Fluorescence methods, Optics and Photonics, and Carmustine

Significance: Hyperspectral imaging (HSI) technologies offer great potential in fluorescence microscopy for multiplexed imaging, autofluorescence removal, and analysis of autofluorescent molecules. However, there are also associated trade-offs when implementing HSI in fluorescence microscopy systems, such as decreased acquisition speed, resolution, or field-of-view due to the need to acquire spectral information in addition to spatial information. The vast majority of HSI fluorescence microscopy systems provide spectral discrimination by filtering or dispersing the fluorescence emission, which may result in loss of emitted fluorescence signal due to optical filters, dispersive optics, or supporting optics, such as slits and collimators. Technologies that scan the fluorescence excitation spectrum may offer an approach to mitigate some of these trade-offs by decreasing the complexity of the emission light path.
Aim: We describe the development of an optical technique for hyperspectral imaging fluorescence excitation-scanning (HIFEX) on a microscope system.
Approach: The approach is based on the design of an array of wavelength-dependent light emitting diodes (LEDs) and a unique beam combining system that uses a multifurcated mirror. The system was modeled and optimized using optical ray trace simulations, and a prototype was built and coupled to an inverted microscope platform. The prototype system was calibrated, and initial feasibility testing was performed by imaging multilabel slide preparations.
Results: We present results from optical ray trace simulations, prototyping, calibration, and feasibility testing of the system. Results indicate that the system can discriminate between at least six fluorescent labels and autofluorescence and that the approach can provide decreased wavelength switching times, in comparison with mechanically tuned filters.
Conclusions: We anticipate that LED-based HIFEX microscopy may provide improved performance for time-dependent and photosensitive assays.
(© 2023 The Authors.)

Humans, Computer Simulation, and Posture physiology

Multi-objective optimization digital human models permit users to predict postures that follow performance criteria, such as minimizing torques. Currently, it is unknown how to weight different objective functions to best predict postures. Objective one was to describe a response surface method to determine optimal objective function weightings to predict lift postures. Objective two was to evaluate the sensitivity of different error calculation methods. Our response surface approach has utility for determining optimal objective function weightings when using a digital human model to evaluate human-system interactions in early design stages. The approach was not dependent on variations in error calculation methods.

Humans, Aged, Caregivers, United Kingdom, Polypharmacy, Frailty, and Deprescriptions

Background: In older people living with frailty, polypharmacy can lead to preventable harm like adverse drug reactions and hospitalization. Deprescribing is a strategy to reduce problematic polypharmacy. All stakeholders should be actively involved in developing a person-centred deprescribing process that involves shared decision-making.
Objective: To co-design an intervention, supported by a logic model, to increase the engagement of older people living with frailty in the process of deprescribing.
Design: Experience-based co-design is an approach to service improvement, which uses service users and providers to identify problems and design solutions. This was used to create a person-centred intervention with the potential to improve the quality and outcomes of the deprescribing process. A 'trigger film' showing older people talking about their healthcare experiences was created and facilitated discussions about current problems in the deprescribing process. Problems were then prioritized and appropriate solutions were developed. The review located the solutions in the context of current processes and procedures. An ideal care pathway and a complex intervention to deliver better care were developed.
Setting and Participants: Older people living with frailty, their informal carers and professionals living and/or working in West Yorkshire, England, UK. Deprescribing was considered in the context of primary care.
Results: The current deprescribing process differed from an ideal pathway. A complex intervention containing seven elements was required to move towards the ideal pathway. Three of these elements were prototyped and four still need development. The complex intervention responded to priorities about (a) clarity for older people about what was happening at all stages in the deprescribing process and (b) the quality of one-to-one consultations.
Conclusions: Priorities for improving the current deprescribing process were successfully identified. Solutions were developed and structured as a complex intervention. Further work is underway to (a) complete the prototyping of the intervention and (b) conduct feasibility testing.
Patient or Public Contribution: Older people living with frailty (and their informal carers) have made a central contribution, as collaborators, to ensure that a complex intervention has the greatest possible potential to enhance the experience of deprescribing medicines.
(© 2022 The Authors. Health Expectations published by John Wiley & Sons Ltd.)

Male, Humans, Swine, Animals, Sentinel Lymph Node Biopsy methods, Lymph Nodes surgery, Indocyanine Green, Surgical Instruments, Robotic Surgical Procedures methods, and Robotics

Fluorescence imaging is increasingly being implemented in surgery. One of the drawbacks of its application is the need to switch back-and-forth between fluorescence- and white-light-imaging settings and not being able to dissect safely under fluorescence guidance. The aim of this study was to engineer 'click-on' fluorescence detectors that transform standard robotic instruments into molecular sensing devices that enable the surgeon to detect near-infrared (NIR) fluorescence in a white-light setting. This NIR-fluorescence detector setup was engineered to be press-fitted onto standard forceps instruments of the da Vinci robot. Following system characterization in a phantom setting (i.e., spectral properties, sensitivity and tissue signal attenuation), the performance with regard to different clinical indocyanine green (ICG) indications (e.g., angiography and lymphatic mapping) was determined via robotic surgery in pigs. To evaluate in-human applicability, the setup was also used for ICG-containing lymph node specimens from robotic prostate cancer surgery. The resulting Click-On device allowed for NIR ICG signal identification down to a concentration of 4.77 × 10 -6  mg/ml. The fully assembled system could be introduced through the trocar and grasping, and movement abilities of the instrument were preserved. During surgery, the system allowed for the identification of blood vessels and assessment of vascularization (i.e., bowel, bladder and kidney), as well as localization of pelvic lymph nodes. During human specimen evaluation, it was able to distinguish sentinel from non-sentinel lymph nodes. With this introduction of a NIR-fluorescence Click-On sensing detector, a next step is made towards using surgical instruments in the characterization of molecular tissue aspects.
(© 2022. The Author(s).)

Male, Humans, Prostate, Proteins, Polymers, Antibodies, Biomarkers, Tumor, and Prostatic Neoplasms diagnosis

Immunoassays are frequently used for analysis of protein biomarkers. The specificity of antibodies enables parallel analysis of several target proteins, at the same time. However, the implementation of such multiplexed assays into cost-efficient and mass-producible thermoplastic microfluidic platforms remains difficult due to the lack of suitable immobilization strategies for different capture antibodies. Here, we introduce and characterize a method to functionalize the surfaces of microfluidic devices manufactured in the thermoplastic material cyclic olefin copolymer (COC) by a rapid prototyping process. A laser-induced immobilization process enables the surface patterning of anchor biomolecules at a spatial resolution of 5 μm. We employ the method for the analysis of prostate cancer associated biomarkers by competitive immunoassays in a microchannel with a total volume of 320 nL, and successfully detected the proteins PSA, CRP, CEA and IGF-1 at clinically relevant concentrations. Finally, we also demonstrate the simultaneous analysis of three markers spiked into undiluted human plasma. In conclusion, this method opens the way to transfer multiplexed immunoassays into mass-producible microfluidic platforms that are suitable for point of care applications.

Over the past few decades, additive manufacturing (AM) has become a reliable tool for prototyping and low-volume production. In recent years, the market share of such products has increased rapidly as these manufacturing concepts allow for greater part complexity compared to conventional manufacturing technologies. Furthermore, as recyclability and biocompatibility have become more important in material selection, biopolymers have also become widely used in AM. This article provides an overview of AM with advanced biopolymers in fields from medicine to food packaging. Various AM technologies are presented, focusing on the biopolymers used, selected part fabrication strategies, and influential parameters of the technologies presented. It should be emphasized that inkjet bioprinting, stereolithography, selective laser sintering, fused deposition modeling, extrusion-based bioprinting, and scaffold-free printing are the most commonly used AM technologies for the production of parts from advanced biopolymers. Achievable part complexity will be discussed with emphasis on manufacturable features, layer thickness, production accuracy, materials applied, and part strength in correlation with key AM technologies and their parameters crucial for producing representative examples, anatomical models, specialized medical instruments, medical implants, time-dependent prosthetic features, etc. Future trends of advanced biopolymers focused on establishing target-time-dependent part properties through 4D additive manufacturing are also discussed.

DNA chemistry, DNA, Single-Stranded, Circular Dichroism, and Quinolines chemistry

Coherently coupled pseudoisocyanine (PIC) dye aggregates have demonstrated the ability to delocalize electronic excitations and ultimately migrate excitons with much higher efficiency than similar designs where excitations are isolated to individual chromophores. Here, we report initial evidence of a new type of PIC aggregate, formed through heterogeneous nucleation on DNA oligonucleotides, displaying photophysical properties that differ significantly from previously reported aggregates. This new aggregate, which we call the super aggregate (SA) due to the need for elevated dye excess to form it, is clearly differentiated from previously reported aggregates by spectroscopic and biophysical characterization. In emission spectra, the SA exhibits peak narrowing and, in some cases, significant quantum yield variation, indicative of stronger coupling in cyanine dyes. The SA was further characterized with circular dichroism and atomic force microscopy observing unique features depending on the DNA substrate. Then by integrating an AlexaFluor TM 647 (AF) dye as an energy transfer acceptor into the system, we observed mixed energy transfer characteristics using the different DNA. For example, SA formed with a rigid DNA double crossover tile (DX-tile) substrate resulted in AF emission sensitization. While SA formed with more flexible non-DX-tile DNA (i.e. duplex and single strand DNA) resulted in AF emission quenching. These combined characterizations strongly imply that DNA-based PIC aggregate properties can be controlled through simple modifications to the DNA substrate's sequence and geometry. Ultimately, we aim to inform rational design principles for future device prototyping. For example, one key conclusion of the study is that the high absorbance cross-section and efficient energy transfer observed with rigid substrates made for better photonic antennae, compared to flexible DNA substrates.
(Creative Commons Attribution license.)

The expanded access to clinical trials has provided more patients the opportunity to participate in novel therapeutics research. There is an increased likelihood of a patient, as a pediatric oncology clinical trial participant, to present for clinical care outside the research site, such as at an emergency room or urgent care center. A novel wearable universal serial bus device is a proposed technology to bridge potential communication gaps, pertaining to critical information such as side effects and permitted therapies, between research teams and clinical teams where investigational agents may be contraindicated to standard treatments. Fifty-five emergency and urgent care nurses across the United States were presented, via online survey without priming to the context of clinical trials or the device, a picture of a pediatric patient wearing the novel wearable device prompted to identify significant, environmental cues important for patient care. Of the 40 nurses observing the patient photo, three identified the wearable device within Situational Awareness Global Assessment Tool formatted narrative response fields. Analysis of the narrative nurse-participant responses of significant clinical findings upon initial assessment of the pediatric patient photo is described, as well as the implications for subsequent prototyping of the novel universal serial bus prototype.
(Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Visual Acuity, Vision, Ocular, Visual Perception physiology, Retina physiology, and Visual Prosthesis

Objective. Visual prostheses currently restore only limited vision. More research and pre-clinical work are required to improve the devices and stimulation strategies that are used to induce neural activity that results in visual perception. Evaluation of candidate strategies and devices requires an objective way to convert measured and modelled patterns of neural activity into a quantitative measure of visual acuity. Approach. This study presents an approach that compares evoked patterns of neural activation with target and reference patterns. A d-prime measure of discriminability determines whether the evoked neural activation pattern is sufficient to discriminate between the target and reference patterns and thus provides a quantified level of visual perception in the clinical Snellen and MAR scales. The magnitude of the resulting value was demonstrated using scaled standardized 'C' and 'E' optotypes. Main results. The approach was used to assess the visual acuity provided by two alternative stimulation strategies applied to simulated retinal implants with different electrode pitch configurations and differently sized spreads of neural activity. It was found that when there is substantial overlap in neural activity generated by different electrodes, an estimate of acuity based only upon electrode pitch is incorrect; our proposed method gives an accurate result in both circumstances. Significance. Quantification of visual acuity using this approach in pre-clinical development will allow for more rapid and accurate prototyping of improved devices and neural stimulation strategies.
(© 2023 IOP Publishing Ltd.)

In the context of the Eu:CROPIS mission requirements, this paper aims to test and validate an intra-spacecraft wireless transmission carried between two SpW-to-UWB Wireless Interface Units (WIUs). The WIUs are designed to replace the on-board SpaceWire (SpW) connections of a spacecraft network. The novelty of this solution resides in prototyping and testing proprietary TRL6 WIUs for the implementation of both PDHU and CDHU units, which constitute a spacecraft network. The validation test scenarios employed in this paper were designed under the Eu:CROPIS mission system requirements as defined by the WiSAT-3 European Space Agency (ESA)-funded project. The SpW-to-UWB WIUs run a custom-built ISA100 over an IEEE 802.15.4 UWB PHY layer communication stack. The WIUs are evaluated based on four mission-specific performance test scenarios: (1) the link setup test, (2) the end-to-end delay test, (3) the maximum data rate test and (4) the housekeeping test. The validation test scenarios of the WIUs are carried out with the use of STAR-Dundee SpW-capable equipment. The test results demonstrate the reliability of the deployed SpW-to-UWB WIUs devices for UWB wireless communications carried out within a space shuttle. The SpW data were successfully transmitted across the intra-spacecraft wireless network in all experimental tests. The technology can be considered to be at the maturity level TRL6 (functionality demonstrated in relevant environment) for LEO missions.

A stencil printing method utilizing sticky notes, a thermal transfer ink ribbon, and office appliances for paper-based analytical device (PAD) fabrication was proposed. A sticky note was attached to a filter paper, and a mask pattern was cut using a cutting machine. A commercially available thermal ink ribbon was then placed over the mask and laminated. We have characterized the fabricated devices. This approach could be used for the fast and mass prototyping of PADs using simple office appliances with no need for a wax printer.

Recent advances in additive manufacturing have provided more freedom in the design of metal parts; hence, the prototyping of fluid machines featuring extremely complex geometries has been investigated extensively. The fabrication of fluid machines via additive manufacturing requires significant attention to part stability; however, studies that predict regions with a high risk of collapse are few. Therefore, a novel algorithm that can detect collapse regions precisely is proposed herein. The algorithm reflects the support span over the faceted surface via propagation and invalidates overestimated collapse regions based on the overhang angle. A heat exchanger model with an extremely complex internal space is adopted to validate the algorithm. Three samples from the model are extracted and their prototypes are fabricated via laser powder bed fusion. The results yielded by the fabricated samples and algorithm with respect to the sample domain are compared. Regions of visible collapse identified on the surface of the fabricated samples are predicted precisely by the algorithm. Thus, the supporting span reflected by the algorithm provides an extremely precise prediction of collapse.

Background: The need for whole mandibular bone reconstruction and bilateral joint replacement is fortunately rare, but it is an extremely challenging topic in maxillofacial surgery, due to its functional implications. CAD-CAM techniques development has opened new broad horizons in the surgical planning of complex maxillofacial reconstructions, in terms of accuracy, predictability, and functional cosmetic results. The review of the literature has revealed a small number of scientific reports on total mandibulectomy including the condyles, with only eleven cases from 1980. Most of the works describe reconstructions secondary to dysplastic or inflammatory diseases affecting the lower jaw. The aim of this work, reporting a rare case of massive fibrous dysplasia of the whole mandible, is to share our experience in the management of extended mandibular and bilateral joint reconstruction, using porous titanium patient-specific implants.
Case Presentation: The authors present a 20-year-old male patient suffering from massive bone fibrous dysplasia of the mandible. The mandibular body and both the rami and the condylar processes had been involved, causing severe functional impairment, tooth loss, and facial deformation. The young patient, after repeated ineffective conservative surgical treatments, has required a biarticular mandibular replacement. Using virtual surgical planning (VSP) software, the authors, in collaboration with medical engineers, have created a custom-made original titanium porous mandibular implant, suspended from a bilateral artificial temporomandibular joint. The mandibular titanium implant body has been specifically designed to support soft tissues and to fix, in the alveolar region, a free fibular bone graft, for delayed dental implant prosthetic rehabilitation.
Conclusion: The surgical and technical details, as well as the new trends in mandibular reconstructions using porous titanium implants, are reported, and discussed, reviewing literature reports on this topic. Satisfactory functional and cosmetic restorative results have been obtained, and no major complications have occurred. The patient, currently in the 18 th month clinical and radiological follow-up, has recently completed the functional restoration program by an implant-supported full-arch dental prosthesis.
(© 2023. The Author(s).)

Dimethylpolysiloxanes, Microfluidics methods, and Microfluidic Analytical Techniques

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

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

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

This paper presents a discontinuous Galerkin (DG) integral equation (IE) method for the electromagnetic analysis of arbitrarily-shaped plasmonic assemblies. The use of nonconformal meshes provides improved flexibility for CAD prototyping and tessellation of the input geometry. The formulation can readily address nonconformal multi-material junctions (where three or more material regions meet), allowing to set very different mesh sizes depending on the material properties of the different subsystems. It also enables the use of h-refinement techniques to improve accuracy without burdening the computational cost. The continuity of the equivalent electric and magnetic surface currents across the junction contours is enforced by a combination of boundary conditions and local, weakly imposed, interior penalties within the junction regions. A comprehensive study is made to compare the performance of different IE-DG alternatives applied to plasmonics. The numerical experiments conducted validate the accuracy and versatility of this formulation for the resolution of complex nanoparticle assemblies.

Humans, Internet, Research Personnel, Software, and Internet of Things

Throughout the evolution of software systems, empirical methodologies have been used in their development process, even in the Internet of Things (IoT) paradigm, to develop IoT-based systems (IoTS). In this paper, we review the fundamentals included in the manifesto for agile software development, especially in the Scrum methodology, to determine its use and role in IoTS development. Initially, 4303 documents were retrieved, a number that was reduced to 186 after applying automatic filters and by the relevance of their titles. After analysing their contents, only 60 documents were considered. Of these, 38 documents present the development of an IoTS using some methodology, 8 present methodologies focused on the construction of IoTS software, and 14 present methodologies close to the systems life cycle (SLC). Finally, only one methodology can be considered SLC-compliant. Out of 38 papers presenting the development of some IoTS following a methodology for traditional information systems (ISs), 42.1% have used Scrum as the only methodology, while 10.5% have used Scrum combined with other methodologies, such as eXtreme Programming (XP), Kanban and Rapid Prototyping. In the analysis presented herein, the existing methodologies for developing IoTSs have been grouped according to the different approaches on which they are based, such as agile, modelling, and service oriented. This study also analyses whether the different proposals consider the standard stages of the development process or not: planning and requirements gathering, solution analysis, solution design, solution coding and unit testing (construction), integration and testing (implementation), and operation and maintenance. In addition, we include a review of the automated frameworks, platforms, and tools used in the methodologies analysed to improve the development of IoTSs and the design of their underlying architectures. To conclude, the main contribution of this work is a review for IoTS researchers and developers regarding existing methodologies, frameworks, platforms, tools, and guidelines for the development of IoTSs, with a deep analysis framed within international standards dictated for this purpose.

Humans, Cities, Urbanization, Public Health, Ecosystem, and Quality of Life

Increasing population and urbanization, with climate change consequences, such as rising temperatures, influence public health and well-being. The search to improve the quality of life in cities becomes one of the priority objectives. A solution can be found in the role of greenery in an urban environment and its impact on human health. This opens a path toward experimentation on microclimate green structures that can be inserted into dense urban spaces providing human and environmental benefits. The article proposes an automated greenery design method combined with rapid prototyping for such interventions. A theoretical analysis of the problem preceded the introduction of the method. The research process was developed in accordance with the main objectives of the CDIO framework (Conceive, Design, Implement, and Operate) with the SiL (Software in the Loop) and HiL (Hardware in the Loop) methods. Moreover, the applied test model allows for complex evaluation in order to ensure quality and directions for further development.

Faithful modeling of tissues and organs requires the development of systems reflecting their dynamic 3D cellular architecture and organization. Current technologies suffer from a lack of design flexibility and complex prototyping, preventing their broad adoption by the scientific community. To make 3D cell culture more available and adaptable we here describe the use of the fused deposition modeling (FDM) technology to rapid-prototype 3D printed perfusion bioreactors. Our 3D printed bioreactors are made of polylactic acid resulting in reusable systems customizable in size and shape. Following design confirmation, our bioreactors were biologically validated for the culture of human mesenchymal stromal cells under perfusion for up to 2 weeks on collagen scaffolds. Microenvironments of various size/volume (6-12 mm in diameter) could be engineered, by modulating the 3D printed bioreactor design. Metabolic assay and confocal microscopy confirmed the homogenous mesenchymal cell distribution throughout the material pores. The resulting human microenvironments were further exploited for the maintenance of human hematopoietic stem cells. Following 1 week of stromal coculture, we report the recapitulation of 3D interactions between the mesenchymal and hematopoietic fractions, associated with a phenotypic expansion of the blood stem cell populations.Our data confirm that perfusion bioreactors fit for cell culture can be generated using a 3D printing technology and exploited for the 3D modeling of complex stem cell systems. Our approach opens the gates for a more faithful investigation of cellular processes in relation to a dynamic 3D microenvironment.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2023 Dupard, Garcia and Bourgine.)

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

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

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

Background: Single-row (SR) and double-row repair techniques have been described to treat rotator cuff tears. We present a novel surgical strategy of arthroscopic-assisted mini-open repair in which a locking-loop suture bridge (LLSB) is used.
Purpose: To compare the functional outcomes and repair integrity of LLSB technique to the SR technique for arthroscopic-assisted mini-open repair of small to medium rotator cuff tears.
Study Design: Cohort study; Level of evidence, 3.
Methods: Included were 39 patients who underwent LLSB repair (LLSB group) and 44 patients who underwent SR suture anchor repair (SR group) from 2015 to 2018. We evaluated all patients preoperatively and at 3, 6, 12, and 24 months postoperatively using the visual analog scale (VAS) for pain, Oxford Shoulder Score (OSS), and American Shoulder and Elbow Surgeons (ASES) score. Also, shoulder sonography was performed at 12 months postoperatively to evaluate repair integrity using the Sugaya classification system. The independent-sample t test was used to analyze functional outcomes (VAS, OSS, and ASES scores), and the Fisher exact test was used to analyze postoperative sonography results.
Results: Patients in both the LLSB and SR groups saw a significant improvement on all 3 outcome measures from preoperatively to 24 months postoperatively ( P < .001 for all). However, when comparing scores between groups, only the scores at 3 months postoperatively differed significantly (VAS: P = .002; OSS: P < .001; ASES: P = .005). Shoulder sonography at 12 months postoperatively revealed no significant difference in repair integrity between the LLSB and SR groups (retear rate: 10.26% and 6.82%, respectively; P = .892).
Conclusion: Better outcome scores were seen at 3-month follow-up in the LLSB group, with no difference in retear rates compared with the SR group at 12 months postoperatively. The LLSB technique was found to be a reliable technique for rotator cuff repair of small- to medium-sized tears.
Competing Interests: The authors declared that there are no conflicts of interest in the authorship and publication of this contribution. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.
(© The Author(s) 2023.)

Design thinking is an approach to problem solving that focuses on a solution to a problem. This systematic approach can be applied to practice-based research or implementation projects in your practice setting. It may be useful for starting new projects as well as revisiting past projects that may not have yielded meaningful results. The design-thinking process begins with identifying a problem or knowledge gap and then the steps include: (1) understanding the problem, (2) observing the problem, (3) defining the problem, (4) brainstorming possible solutions, (5) prototyping the best solution, and (6) testing the solution.

The spread of additive manufacturing techniques in the prototyping and realization of high-frequency applications renewed the interest in the characterization of the electromagnetic properties of both dielectric and conductive materials, as well as the design of new versatile measurement techniques. In this framework, a new configuration of a dielectric-loaded resonator is presented. Its optimization, realization, and use are presented. A measurement repeatability of about one order of magnitude lower than the commonly found values (10-3 on the Q -factor and 15×10-6 on the resonance frequency, given in terms of the relative standard deviations of repeated measurements) was reached thanks to the design of a closed resonator in which the samples can be loaded without disassembling the whole measurement fixture. The uncertainty levels, the ease of use, and the versatility of the realized system make its use of potential interest in numerous scenarios.

The mechanisms of deep-hole microdrilling of pure Mg material were experimentally studied in order to find a suitable setup for a novel intraocular drug delivery device prototyping. Microdrilling tests were performed with 0.20 mm and 0.35 mm microdrills, using a full factorial design in which cutting speed vc and feed fz were varied over two levels. In a preliminary phase, the chip shape was evaluated for low feeds per tooth down to 1 μm, to verify that the chosen parameters were appropriate for machining. Subsequently, microdrilling experiments were carried out, in which diameter, burr height and surface roughness of the drilled holes were examined. The results showed that the burr height is not uniform along the circumference of the holes. In particular, the maximum burr height increases with higher cutting speed, due to the thermal effect that plasticizes Mg. Hole entrance diameters are larger than the nominal tool diameters due to tool runout, and their values are higher for high vc and fz. In addition, the roughness of the inner surface of the holes increases as fz increases.

Inkjet printing remains one of the most cost-efficient techniques for device prototyping and manufacturing, offering considerable freedom of digital design, non-contact, and additive fabrication. When developing novel wearable devices, a balanced approach is required between functional, user-safe materials and scalable manufacturing processes. Here, we propose a tailor-made ink formulation, based on non-hazardous materials, to develop green electronic devices aimed at interfacing with humans. We demonstrate that developed ink exhibits high-resolution inkjet printability, in line with theoretical prediction, on multiple wearable substrates. The ink's chemical composition ensures the pattern's enhanced electrical properties, mechanical flexibility, and stability in water. The cytocompatibility evaluations show no noxious effects from printed films in contact with human mesenchymal stem cells. Finally, we fabricated a printed wearable touch sensor on a non-woven fabric substrate, capable of tracking human steps. This is a step toward the development of green wearable electronics manufacturing, demonstrating a viable combination of materials and processes for biocompatible devices.
(© 2023 Author(s).)

In recent years, the quantity and complexity of medical imaging acquisition and processing have increased tremendously. The explosion in volume and need for advanced imaging analysis have led to the creation of numerous software programs, which have begun to be incorporated into clinical practice for indications such as automated stroke assessment, brain tumor perfusion processing, and hippocampal volume analysis. Despite these advances, there remains a need for specialized, custom-built software for advanced algorithms and new areas of research that is not widely available or adequately integrated in these "out-of-the-box" solutions. The purpose of this paper is to describe the implementation of an image-processing pipeline that is versatile and simple to create, which allows for rapid prototyping of image analysis algorithms and subsequent testing in a clinical environment. This pipeline uses a combination of Orthanc server, custom MATLAB code, and publicly available FMRIB Software Library and RestNeuMap tools to automatically receive and analyze resting-state functional MRI data collected from a custom filter on the MR scanner output. The processed files are then sent directly to Picture Archiving and Communications System (PACS) without the need for user input. This initial experience can serve as a framework for those interested in simple implementation of an automated pipeline customized to clinical needs.
(© 2022. The Author(s) under exclusive licence to Society for Imaging Informatics in Medicine.)

Bees, Animals, and Pesticides

Interactive maps can serve as powerful environmental decision-support tools. However, designing an interactive map that meets the needs of diverse constituencies is a challenge. In this article, we evaluate and characterize user needs for an interactive map and spatial decision-support tool called Beescape. Beescape is designed to visualize resources and environmental risks to bees and other pollinators (such as availability of nutritional resources from flowering plants and exposure to pesticides) in order to help users make informed decisions about managing bee populations and associated landscapes. We conducted a needs assessment workshop with twenty stakeholders from four user groups including beekeepers, growers, conservationists, and pollinator scientists to elicit their knowledge to guide future Beescape development. The results of the workshop identify current analytical gaps with the existing Beescape prototype, including the need for predictive and historical tools, more actionable data layers, finer-grain spatial data, and better explanations on what data represent and how they were created. Our findings on user's analytical, informational, and interface needs can be utilized to guide the future development of spatial decision support tools like Beescape, and our methodological approach may apply to other environmental informatics tools where it is important to design for multiple constituent user groups.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Timothy J. Prestby reports financial support was provided by United States Department of Agriculture. Anthony C. Robinson reports financial support was provided by United States Department of Agriculture and Agriculture. Christina M. Grozinger reports financial support was provided by United States Department of Agriculture.
(Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Silicon Dioxide, Staphylococcus aureus, Escherichia coli, Biocompatible Materials chemistry, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents chemistry, Polymers, Printing, Three-Dimensional, Glass chemistry, Tissue Scaffolds chemistry, Porosity, Silver pharmacology, and Metal Nanoparticles

The development of new biomaterials for bone tissue regeneration with high bioactivity abilities and antibacterial properties is being intensively investigated. We have synthesized nanocomposites formed by mesoporous bioactive glasses (MBGs) in the ternary SiO 2 , CaO and P 2 O 5 system doped with metallic silver nanoparticles (AgNPs) that were homogenously embedded in the MBG matrices. Ag/MBG nanocomposites have been directly synthesized and silver species were spontaneously reduced to metallic AgNPs by high temperatures (700 °C) obtained of last MBG synthesis step. Three-dimensional silver-containing mesoporous bioactive glass scaffolds were fabricated showing uniformly interconnected ultrapores, macropores and mesopores. The manufacture method consisted of a combination of a single-step sol-gel route in the mesostructure directing agent (P123) presence and a biomacromolecular polymer such as (hydroxypropyl)methyl cellulose (HPMC) as the macrostructure template, followed by rapid prototyping (RP) technique. Biological properties of Ag/MBG nanocomposites were evaluated by MC3T3-E1 preosteoblastic cells culture tests and bacterial (E. coli and S. aureus) assays. The results showed that the MC3T3-E1 cells morphology was not affected while preosteoblastic proliferation decreased when the presence of silver increased. Antimicrobial assays indicated that bacterial growth inhibition and biofilm destruction were directly proportional to the increased presence of AgNPs in the MBG matrices. Furthermore, in vitro co-culture of MC3T3-E1 cells and S. aureus bacteria confirmed that AgNPs presence was necessary for antibacterial activity, and AgNPs slightly affected cell proliferation parameters. Therefore, 3D printed scaffolds with hierarchical pore structure and high antimicrobial capacity have potential applications in bone tissue regeneration. STATEMENT OF SIGNIFICANCE: This study combines three key scientific aspects for bone tissue engineering: (i) materials with high bioactivity to repair and regenerate bone tissue that (ii) contain antibacterial agents to reduce the infection risk (iii) in the form of three-dimensional scaffolds with hierarchical porosity. Innovative methodology is described here: sol-gel method, which is employed to obtain mesoporous bioactive glass matrices doped with metallic silver nanoparticles where different polymer templates facilitate the different size scales presence, and rapid prototyping technique that provides ultra-large macroporosity according to computer-aided design. The dual scaffolds obtained are biocompatible and deliver active doses of silver capable of combating bone infections, which represent one of the most serious complications associated to surgical treatments of bone diseases and fractures.
Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest.
(Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Humans, Titanium, Pilot Projects, Surgical Mesh, Orbit surgery, Plastic Surgery Procedures, Dental Implants, Orbital Fractures diagnostic imaging, and Orbital Fractures surgery

Objective: The aim was to preliminarily evaluate the effect of individualized preformed titanium mesh in the treatment of orbital wall fractures with superior orbital fissure syndrome (SOFS).
Study Design: This study consisted of 10 patients of orbital wall fracture and SOFS who were treated at the Affiliated Stomatology Hospital of Southwest Medical University. On the basis of preoperative computed tomography data, individualized titanium mesh was produced by mirror engineering and rapid prototyping, and it was implanted into defects in the orbital walls to restore the normal anatomy. Early orbital wall reconstruction was performed to improve the SOFS. Postoperatively, the ocular and facial appearance and eye function were evaluated.
Results: The orbital structure, volume, and size of the SOF were restored in the 10 patients using the individualized titanium mesh. The symptoms of SOFS completely disappeared in all patients with no severe postoperative complications. Significant recovery of ocular and facial appearance and eye function was reported.
Conclusions: This pilot study demonstrated that individualized preformed titanium mesh can accurately restore the orbital walls and the structure and size of the SOF, and it is useful in the treatment of SOFS without intraorbital bone fragment displacement.
(Copyright © 2022 Elsevier Inc. All rights reserved.)

Game development is a collective process in which a variety of different professionals from different backgrounds collaborate together not only by means of conversational interaction but also collaborative participation, one of which is programming. While collaborative and pair programming solutions exist for text-based programming languages, visual programming has not enjoyed as much attention. These solutions would not only address advanced forms of business communication among team members but could find their use in distance learning, which would have been useful during the pandemic. In our work, we propose a solution for collaborative behavioral animation of NPCs using behavior trees through synchronous and asynchronous modes of collaboration. We conducted a user study with 12 moderately skilled game development university students who were placed in groups of two and engaged in joint fixed behavior tree development tasks using the synchronous and asynchronous modes and auxiliary features of live preview, access and restoration of previous states from behavior tree history, conflict resolution, and instant messaging. Participants also completed a control task where no collaboration was involved and auxiliary features were not available. Feedback form Creativity Support Index, a self-developed questionnaire, and a semi-structured interview were collected. Additionally, task completion times were logged. The results indicate that the two collaborative modes provide expected improvement over the control condition. No significant differences were found between the two collaborative modes. However, the semi-structed interview revealed that the synchronous mode could be useful for quick prototyping, while the asynchronous mode - for most other situations.
Supplementary Information: The online version contains supplementary material available at 10.1007/s11042-022-12307-2.
Competing Interests: Conflict of interestAuthors declare that they have no conflict of interest.
(© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022.)

The COVID-19 pandemic made being socially distant an essential practice to upskill employees. As employers incorporate measures to keep employees socially distant from one another, they also need to consider technology to make this practice possible. Our project with a large state-wide, multi-campus food bank (FB) in the pacific northwest occurred during the late summer and early fall of 2020. The FB partnered with our group of three graduate students and one faculty member to improve self-audits of their coolers. This project used technology and rapid prototyping to design an instructional intervention that allowed social distancing in a workplace where employees were required to be present. We conducted a front-end analysis including training requirements, learner and environmental analysis and task analysis. This article describes the process of the analyses and design of instructional materials that allowed the FB to scale their audit process to their other warehouses.
(© Association for Educational Communications & Technology 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)