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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.)

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).)

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: The Quick Exposure Check (QEC) assesses four major body parts and engages users in assessing some physical interactions relevant to design in task analysis.
Objective: In this paper, we investigated the application of QEC as the ergonomic intervention to detect pre-production ergonomic design faults in the apple sorting machine by applying physical and virtual prototyping for three different tasks analysis divided into two phases (Task 1: Apple harvesting and preparation for sorting; Task 2: Sorting control and separation of waste fruits; Task 3: Transfer of separated apples).
Method: First, the QEC questionnaire was administered while Iranian participants interacted with the machine to detect abnormal posture. Second, we redesigned a concept of the machine and assessed it with QEC by a focus group.
Results: Before design, the high pressure in Task 1 is on the back (dynamic), shoulder/arm, and very high pressure in Task 2, and in Task 3 on the back (static), arm/shoulder/neck, making an uncomfortable situation for posture. After redesign, we observed decreased pressures on the back/shoulder/arm in Task 1 from high to medium, in Task 3 from very high to low, and also in Task 2, this was detectable decreasing from very high pressures on the back/shoulder/arm and the high pressures on the neck to medium.
Conclusion: Prototyping with QEC demonstrated that accurate redesigning of the machine with concentration on shifting from static tasks to dynamic or conversely, and ease of access by adjusting dimensions according to anthropometry and auxiliary products, could reduce musculoskeletal disorders.

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.)

Background: The applications and scope of digitization and technology in dentistry are becoming increasingly valuable right from clinical dentistry to research, student training, teaching, and laboratory techniques. Mastering 3D printing and its usage are essential for dental practitioners and dental technicians as it allows them to choose and necessarily know what is offered, as well as how to implement it in everyday practices thereby contributing to the betterment of the dental profession. The study aims to assess dental practitioners' and dental technicians' knowledge, understanding, and practices related to the use of 3D printing in dentistry.
Methods: A cross-sectional questionnaire-based study was done among dental practitioners and technicians in Karnataka, India who were given access to a self-explanatory questionnaire via Google link consisting of questions that evaluated their knowledge, awareness, and practices regarding 3D printing. The Chi-square test was used for statistical analysis.
Results: A total of 380 replies were obtained after the questionnaire was circulated. Awareness regarding the use of digital technology in dentistry was known by 98.9% of practitioners and 92.7% of technicians, of which we discovered that 9.28% of practitioners and 17.7% of technicians were unfamiliar with 3D printing, which was statistically significant (p = 0.0400*). 81.6% of practitioners consider 3D printing can be used to fabricate complex design prostheses.
Conclusion: The participants' understanding of digital dentistry and 3D printing is acceptable. The majority of dental professionals expressed an interest in adopting 3D printing and believe that there should be a forum for collecting and exchanging skills and knowledge about 3D printing.
Competing Interests: No potential conflict of interest relevant to this article was reported.
(© 2023 The Authors.)

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).)

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.

Microneedle-based transdermal drug delivery into the skin has gained attraction for the past few years. An affordable and effective fabrication methodology is required for the development of micron size needle. Manufacturing cost-effective microneedle patches in batch production is a challenging process. In this work, we proposed a cleanroom-free technique for fabrication of conical and pyramidal geometry of microneedle array for transdermal drug delivery. Using the COMSOL Multiphysics tool, the mechanical strength of the designed microneedle array under axial, bending, and buckling loads for the geometries during skin insertion was investigated. A CO 2 laser and polymer molding technique are used to fabricate 10 × 10 designed microneedle array structure. On an acrylic sheet, a designed pattern is engraved to produce a 20 mm × 20 mm sharp conical and pyramidal shape master mold. We successfully created a biocompatible polydimethylsiloxane (PDMS) microneedle patch with an average height of 1200 µm, base diameter of 650 µm, and a tip diameter of 50 µm using acrylic master mold. According to structural simulation analysis, the microneedle array will experience resultant stress that is within a safe range. The mechanical stability of the fabricated microneedle patch was investigated using hardness test and universal testing machine. The depth of penetration studies were performed in an in vitro Parafilm ® M model by manual compression tests and its detailed insertion depth was reported. The developed master mold is efficient to replicate several polydimethylsiloxane microneedle patches. The proposed combined method of laser processing and molding mechanism is simple and low-cost for rapid prototyping of microneedle array.
(© 2023. Controlled Release Society.)

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.