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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.)