articles+ search results

Traveling wave structures for lossless ion manipulation (TW-SLIM) has proven a valuable tool for the separation and study of gas-phase ions. Unfortunately, many of the traditional components of TW-SLIM experiments manifest practical and financial barriers to the technique's broad implementation. To this end, a series of technological innovations and methodologies are presented which enable for simplified SLIM experimentation and more rapid TW-SLIM prototyping. In addition to the use of multiple independent board sets that comprise the present SLIM system, we introduce a low-cost, multifunctional traveling wave generator to produce TW within the TW-SLIM. This square-wave producing unit proved effective in realizing TW-SLIM separations compared to traditional approaches. Maintaining a focus on lowering barriers to implementation, the present set of experiments explores the use of on-board injection (OBI) methods, which offer potential alternatives to ion funnel traps. These OBI techniques proved feasible and the ability of this simplified TW-SLIM platform to enhance ion accumulation was established. Further experimentation regarding ion accumulation revealed a complexity to ion accumulation within TW-SLIM that has yet to be expounded upon. Lastly, the ability of the presented TW-SLIM platform to store ions for extended periods (1 s) without significant loss (<10%) was demonstrated. The aforementioned experiments clearly establish the efficacy of a simplified TW-SLIM platform which promises to expand adoption and experimentation of the technique.
(Copyright © 2022 Elsevier B.V. All rights reserved.)

Colorimetry methods, Humans, Microfluidics, Paper, Printing, Three-Dimensional, Reproducibility of Results, Drinking Water analysis, and Nitrites

To ensure safe drinking water, it is necessary to have a simple method by which the probable pollutants are detected at the point of distribution. Nitrite contamination in water near agricultural locations could be an environmental concern due to its deleterious effects on the human population. The development of a frugal paper-based microfluidic sensor could be desirable to achieve the societal objective of providing safe drinking water. This work describes the development of a facile and cost-effective microfluidic paper-based sensor for quantitative estimation of nitrite in aquatic environments. A simple punching machine was used for fabrication and rapid prototyping of paper-based sensors without the need of any specialized equipment or patterning techniques. A reusable 3D printed platform served as the support for simultaneous testing of multiple samples. The nitrite estimation was carried out with smartphone-assisted digital image acquisition and colorimetric analysis. Under optimized experimental conditions, the variation in average grayscale intensity with concentration of nitrite was linear in the range from 0.1 to 10 ppm. The limits of detection and quantitation were 0.12 ppm and 0.35 ppm respectively. The reproducibility, expressed as relative standard deviation was 1.31%. The selectivity of nitrite detection method was determined by performing interference studies with commonly existing co-ions in water, such as bicarbonates, chloride and sulphate. The paper-based sensor was successfully applied for estimation of nitrite in actual water samples and showed high recoveries in the range of 83.5-109%. The results were in good agreement with those obtained using spectrophotometry. The developed paper-based sensor method, by virtue of its simplicity, ease of fabrication and use, could be readily extended for detection of multiple analytes in resource-limited settings.
(Copyright © 2022 Elsevier Inc. All rights reserved.)

Engineering regulatory parts for improved performance in genetic programs has played a pivotal role in the development of the synthetic biology cell programming toolbox. Here, we report the development of a novel high-throughput platform for regulatory part prototyping and analysis that leverages the advantages of engineered DNA libraries, cell-free protein synthesis (CFPS), high-throughput emulsion droplet microfluidics, standard flow sorting adapted to screen droplet reactions, and next-generation sequencing (NGS). With this integrated platform, we screened the activity of millions of genetic parts within hours, followed by NGS retrieval of the improved designs. This in vitro platform is particularly valuable for engineering regulatory parts of nonmodel organisms, where in vivo high-throughput screening methods are not readily available. The platform can be extended to multipart screening of complete genetic programs to optimize yield and stability.

Additive Manufacturing (AM) comprises a variety of techniques that enable fabrication of customised objects with specific attributes. The versatility of AM procedures and constant technological improvements allow for their application in the development of medicinal products and medical devices. This review provides an overview of AM applications related to respiratory sciences. For this purpose, both fields of research are briefly introduced and the potential benefits of integrating AM to respiratory sciences at different levels of pharmaceutical development are highlighted. Tailored manufacturing of microstructures as a particle design approach in respiratory drug delivery will be discussed. At the dosage form level, we exemplify AM as an important link in the iterative loop of data driven inhaler design, rapid prototyping and in vitro testing. This review also presents the application of bioprinting in the respiratory field for design of biorelevant in vitro cellular models, followed by an overview of AM-related processes in preventive and therapeutic care. Finally, this review discusses future prospects of AM as a component in a digital health environment.
(Copyright © 2022. Published by Elsevier B.V.)

Purpose: An automated algorithm for generating realizable MR gradient and shim coil layouts based on the boundary element method is presented here. The overall goal is to reduce postprocessing effort and thus enable for rapid prototyping of new coil designs. For a given surface mesh and target field, the algorithm generates a connected, non-overlapping wire path.
Methods: The proposed algorithm consists of several steps: Stream function optimization, two-dimensional surface projection, potential discretization, topological contour sorting, opening and interconnecting contours, and finally adding non-overlapping return paths. Several technical parameters such as current strength, inductance and field accuracy are assessed for quality control.
Results: The proposed method is successfully demonstrated in four different examples. All exemplary results demonstrate high accuracy with regard to reaching the respective target field. The optimal discretization for a given stream function is found by generating multiple layouts while varying the input parameter values.
Conclusion: The presented algorithm allows for a rapid generation of interconnected coil layouts with high flexibility and low discretization error. This enables to reduce the overall post-processing effort. The source code of this work is publicly available ( https://github.com/Philipp-MR/CoilGen).
(© 2022 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Background: Temporal hollowing is a common complication following the rotation of the temporalis muscle that leaves the patient with a cosmetic impairment. Several alloplastic materials have been used to reconstruct the donor site; however, these implants need meticulous adaptation to conform the periphery of the defect and restore the contour of the temporal area. The aim of this study was to assess the use of patient-specific polyetheretherketone (PEEK) temporal implants to prevent temporal hollowing following the use of full temporalis muscle flap for large maxillary defects reconstruction.
Methods: This was a prospective study conducted on eight patients with major maxillary defects indicating the need of reconstruction with full temporalis muscle flap or any lesion indicating major maxillary resection and immediate reconstruction with total temporalis muscle flap. For each patient, a patient-specific PEEK implant was fabricated using virtual planning and milled from PEEK blocks. In the surgical theater, the temporalis muscle was exposed, elevated, and transferred to the maxilla. After the temporalis muscle transfer, PEEK implants were fixed in place to prevent temporal hollowing.
Results: The surgical procedures were uneventful for all patients. The esthetic result was satisfactory with no post-operative complications except in one patient where seroma occurred after 2 weeks and resolved after serial aspiration.
Conclusion: Patient-specific PEEK implant appears to facilitate the surgical procedures eliminate several meticulous steps that are mainly based on the surgeon's experience.
Trial Registration: Clinical trials registration: NCT05240963 .
(© 2022. The Author(s).)

Purpose: This study compared the dimensional changes between computer-aided design and computer-aided manufacturing (CAD-CAM) milled complete denture bases (CDBs) and three-dimensional (3D) printed CDBs.
Materials and Methods: One maxillary completely edentulous stone model was fabricated with three reference points at the incisive papilla, right molar, and left molar areas marked as X, Y, and Z, respectively. It was scanned to produce a standard tessellation language (STL) file, which was imported to a metal milling machine software to produce the metal model. This metal model was used to fabricate 30 CDBs for analysis. The CDBs were divided into three groups (n = 10 each) according to the fabrication method used as follows: Group 1, CAD-CAM milled CDBs; Group 2, 3D printed CDBs; and Group 3, conventional compression molded CDBs. The CDBs of all groups were scanned after fabrication, and the dimensional changes in each were evaluated by two methods. The first was the two-dimensional evaluation method that involved linear measurement of the distances between the reference points (X-Y, X-Z, and Y-Z) of the scanned reference cast and dentures. The second method was the 3D evaluation method that involved the superimposition of the STL files of the dentures on the STL file of the reference cast. Data were calculated and were statistically analyzed using one-way analysis of variance and Tukey's pairwise post hoc tests.
Results: There was a significant difference in the dimensional accuracy between the CAD-CAM milled, 3D printed, and conventional compression molded CDBs (p < 0.05).
Conclusion: The dimensional accuracy of the CAD-CAM milling system in complete denture fabrication is superior to that of the compression molding and 3D printing systems.
(© 2022 by the American College of Prosthodontists.)

An electrochemical multi-scale model framework for the simulation of arbitrarily three-dimensional structured electrodes for lithium-ion batteries is presented. For the parameterisation, the electrodes are structured via laser ablation, and the model is fit to four different, experimentally electrochemically tested cells. The parameterised model is used to optimise the parameters of three different pattern designs, namely linear, gridwise, and pinhole geometries. The simulations are performed via a finite element implementation in two and three dimensions. The presented model is well suited to depict the experimental cells, and the virtual optimisation delivers optimal geometrical parameters for different C-rates based on the respective discharge capacities. These virtually optimised cells will help in the reduction of prototyping cost and speed up production process parameterisation.

Background: The rise of digital methods and computational tools has opened up the possibility of collecting and analyzing data from novel sources, such as discussions on social media. At the same time, these methods and tools introduce a dependence on technology, often resulting in a need for technical skills and expertise. Researchers from various disciplines engage in empirical bioethics research, and software development and similar skills are not usually part of their background. Therefore, researchers often depend on technical experts to develop and apply digital methods, which can create a bottleneck and hinder the broad use of digital methods in empirical bioethics research.
Objective: This study aimed to develop a research platform that would offer researchers the means to better leverage implemented digital methods, and that would simplify the process of developing new methods.
Methods: This study used a mixed methods approach to design and develop a research platform prototype. I combined established methods from user-centered design, rapid prototyping, and agile software development to iteratively develop the platform prototype. In collaboration with two other researchers, I tested and extended the platform prototype in situ by carrying out a study using the prototype.
Results: The resulting research platform prototype provides three digital methods, which are composed of functional components. This modular concept allows researchers to use existing methods for their own experiments and combine implemented components into new methods.
Conclusions: The platform prototype illustrates the potential of the modular concept and empowers researchers without advanced technical skills to carry out experiments using digital methods and develop new methods. However, more work is needed to bring the prototype to a production-ready state.
(©Manuel Schneider. Originally published in JMIR Formative Research (https://formative.jmir.org), 05.05.2022.)

Electrodes, Glucose, Gold chemistry, Hydrogen Peroxide, Silver, Electrochemical Techniques, and Microfluidics

We present a low-cost, accessible, and rapid fabrication process for electrochemical microfluidic sensors. This work leverages the accessibility of consumer-grade electronic craft cutters as the primary tool for patterning of sensor electrodes and microfluidic circuits, while commodity materials such as gold leaf, silver ink pen, double-sided tape, plastic transparency films, and fabric adhesives are used as its base structural materials. The device consists of three layers, the silver reference electrode layer at the top, the PET fluidic circuits in the middle and the gold sensing electrodes at the bottom. Separation of the silver reference electrode from the gold sensing electrodes reduces the possibility of cross-contamination during surface modification. A novel approach in mesoscale patterning of gold leaf electrodes can produce generic designs with dimensions as small as 250 μm. Silver electrodes with dimensions as small as 385 μm were drawn using a plotter and a silver ink pen, and fluid microchannels as small as 300 μm were fabricated using a sandwich of iron-on adhesives and PET. Device layers are then fused together using an office laminator. The integrated microfluidic electrochemical platform has electrode kinetics/performance of Δ Ep = 91.3 mV, Ipa / Ipc = 0.905, characterized by cyclic voltammetry using a standard ferrocyanide redox probe, and this was compared against a commercial screen-printed gold electrode (Δ Ep = 68.9 mV, Ipa / Ipc = 0.984). To validate the performance of the integrated microfluidic electrochemical platform, a catalytic hydrogen peroxide sensor and enzyme-coupled glucose biosensors were developed as demonstrators. Hydrogen peroxide quantitation achieves a limit of detection of 0.713 mM and sensitivity of 78.37 μA mM -1 cm -2 , while glucose has a limit of detection of 0.111 mM and sensitivity of 12.68 μA mM -1 cm -2 . This rapid process allows an iterative design-build-test cycle in under 2 hours. The upfront cost to set up the system is less than USD 520, with each device costing less than USD 0.12, making this manufacturing process suitable for low-resource laboratories or classroom settings.

Problem: Physicians are playing a growing role as clinician-innovators. Academic physicians are well-positioned to contribute to the medical device innovation process, and yet few medical school curricula provide students opportunities to learn the conceptual framework for clinical needs finding, needs screening, concept generation and iterative prototyping, and intellectual property management. This framework supports innovation and encourages the development valuable interdisciplinary communication skills and collaborative learning strategies.
Approach: Our university offers a novel 3-year-long medical student Longitudinal Interdisciplinary Elective in Biodesign (MSLIEB) that teaches medical device innovation in 4 stages: (1) seminars and small group work, (2) shared clinical experiences for needs finding, (3) concept generation and product development by serving as consultants for biomedical engineering capstone projects, and (4) reflection and mentorship. The MSLIEB objectives are to: create a longitudinal interdisciplinary peer mentorship relationship between undergraduate biomedical engineering students and medical students; and encourage codevelopment of professional identities in relation to medical device innovation.
Outcomes: The MSLIEB enrolled 5 entering cohorts from 2017-2021 with a total of 37 medical student participants. The first full entering cohort of 12 medical students produced 8 mentored biomedical engineering capstone projects, 7 of which were based on clinical needs statements derived from earlier in the elective. Medical student participants have coauthored poster and oral presentations, contributed to projects that won WolfieTank, a university-wide competition modeled after the television show Shark Tank, and participated in the filing of provisional patents. Students reflecting on the course reported a change in their attitude towards existing medical problems, felt better-equipped to collaboratively design solutions for clinical needs, and considered a potential career path in device design.
Next Steps: The MSLIEB will be scaled-up by recruiting additional faculty, broadening clinical opportunities to include the outpatient setting, and increasing medical student access to rapid prototyping equipment.

Humans, Oxides, Printing, Three-Dimensional, Radiography, Strontium, and Acquired Immunodeficiency Syndrome

The aim of this research was to assess a selection of radiopaque filler compounds for increasing radiopacity in a resin suitable for Polyjet multi-material 3D printing. A radiopaque resin has potential applications in medicine to produce patient-specific anatomical models with realistic radiological properties, training aids, and skin contacting components such as surgical or procedural guides that require visibility under fluoroscopy. The desirable filler would have a high level of radiopacity under ionising imaging modalities, such as X-ray, CT, fluoroscopy or angiography. Nine potential filler compounds were selected based on atomic number and handling risk: barium sulphate, bismuth oxide, zirconium oxide, strontium oxide, strontium fluoride, strontium carbonate, iodine, niobium oxide and tantalum oxide. The fillers were evaluated using selected criteria. A weighted material selection matrix was developed to prioritise and select a filler for future 3D printing on a multi-material 3D printer. Zirconium oxide was the highest scoring filler compound in the material selection matrix, scoring 4.4 out of a maximum of 5. MED610 TM resin doped with zirconium oxide was shown to be UV curable, and when cured is non-toxic, environmentally friendly, and has the ability to display antimicrobial properties. In terms of radiopacity, a sample with thickness 1.5 mm of MED610™ resin doped with 20 wt.% zirconium oxide produced X-ray radiopacity equivalent to 3 mm of aluminium. Zirconium oxide was selected using the material selection matrix. This radiopaque resin can be used to produce anatomical models with accurate radiological properties, training aids or skin contacting devices that require visibility under ionising imaging modalities. The 3D printing validation run successfully demonstrated that the material selection matrix prioritised a filler suitable for radiopaque multi-material 3D printing.

Rehabilitation of a post-exenterated orbital defect is a necessity, to restore a patient's esthetic appearance and help overcome the associated psychosocial stigma. An implant supported prosthesis enjoys a better patient acceptance due to its superior retention and stability. This clinical report highlights the challenges faced in planning, designing and placement of maxillofacial implants in the supra-orbital rim of an exenterated socket post-radiotherapy along with the management of the unexpected complications which developed subsequently. Administration of hyperbaric oxygen therapy, fabrication of a digitally designed surgical guide to ensure predictable implant placement, selection of surface treated implants for better biomechanical anchorage, and a gentler surgical technique for recovery of irradiated hard and soft tissues were measures undertaken during the treatment phase. An effort has been made to point-out the fact that despite the various approaches adopted in an irradiated patient, success of implant placement in such a situation remains a challenge.
(© 2022 Craniofacial Research Foundation. Published by Elsevier B.V. All rights reserved.)

Curriculum, Humans, Physical Education and Training, Schools, Educational Personnel, and Students

School-based programs may be more effective when an array of stakeholders, including users, are involved during the relevant stages of program co-creation-specifically during key development stages such as design, implementation and evaluation. How such programs can be operationally co-created and tested is less known and is therefore the purpose of this article. Two sequential co-design phases underpin this study. First, a co-design session with 20 health and physical education (HPE) teachers focussed on reviewing, testing and critically discussing initial prototype online modules for an alcohol education program. Teacher insights were assessed and incorporated, and the updated online modules were tested with secondary school students (n = 120) capturing their experience in a classroom setting. Insights from each group were analysed using thematic analysis. Teachers and students serve important roles in program co-creation. Teachers remain an underutilized stakeholder group whom are however critical in delivering important insights to enhance educational program design. Teachers demanded more relevance to the national curriculum, further alignment with curriculum assessment standards, and age appropriate content. Student feedback focussed largely on realistic content, personalization and gamification elements. This study represents an application of the seven-step co-design process and advances understanding of the 'fuzzy back-end' of the process, namely reflecting on feasibility of integrating teacher and student feedback and ideas. More specifically, how these key-yet distinct-stakeholder groups can be involved, and the merits of their involvement are discussed.
(© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The nanophotonic engineering of light-matter interactions has profoundly changed research behind the design and fabrication of optical materials and devices. Metasurfaces-arrays of subwavelength nanostructures that interact resonantly with electromagnetic radiation-have emerged as an integral nanophotonic platform for a new generation of ultrathin lenses, displays, polarizers and other devices. Their success hinges on advances in lithography and nanofabrication in recent decades. While existing nanolithography techniques are suitable for basic research and prototyping, issues of cost, throughput, scalability, and substrate compatibility may preclude their use for many metasurface applications. Patterning via spontaneous self-assembly of block copolymer thin films offers an enticing alternative for nanophotonic manufacturing that is rapid, inexpensive, and applicable to large areas and diverse substrates. This review discusses the advantages and disadvantages of block copolymer-based nanopatterning and highlights recent progress in their use for broadband antireflection, surface enhanced Raman spectroscopy, and other nanophotonic applications. Recent advances in diversification of self-assembled block copolymer nanopatterns and improved processes for enhanced scalability of self-assembled nanopatterning using block copolymers are also discussed, with a spotlight on directions for future research that would enable a wider array of nanophotonic applications.
(© 2022 US Government.)

Microwave undulators (MUs) have great potential to be an alternative solution to permanent magnet undulators in a free electron laser (FEL) when shorter undulator periods are required. In this paper, the factors that affect the choice of the high-power drive sources were studied via a Ka-band cavity-type MU with a corrugated waveguide proposed for the CompactLight X-ray FEL. They include the technology of the high-power vacuum electronic devices, the quality factor of the MU cavity that was demonstrated by prototyping a short section of the MU structure, and the beam dynamic study of the electrons' trajectories inside the MU. It showed that at high beam energy, a high-power oscillator is feasible to be used as the drive source. At low beam energy, the maximum transverse drift distance becomes larger therefore an amplifier has to be used to minimize the drift distance of the electrons by controlling the injection phase.
(© 2022. The Author(s).)

Adolescent, Adult, Anti-Retroviral Agents therapeutic use, Continuity of Patient Care, Humans, Mozambique, Pilot Projects, Public Health, HIV Infections drug therapy, and Medication Adherence

Adolescents and young people represent a growing proportion of people living with HIV (AYAHIV), and there is an urgent need to design, implement, and test interventions that retain AYAHIV in care. Using a human-centered design (HCD) approach, we codesigned CombinADO, an intervention to promote HIV viral suppression and improve antiretroviral therapy (ART) adherence and retention in care among AYAHIV in Nampula, Mozambique. The HCD process involves formative design research with AYAHIV, health care providers, parents/caretakers, and experts in adolescent HIV; synthesis of findings to generate action-oriented insights; ideation and prototyping of intervention components; and a pilot study to assess feasibility, acceptability, and uptake of intervention components.CombinADO promotes ART adherence and retention in care by fostering peer connectedness and belonging, providing accessible medical knowledge, demystifying and destigmatizing HIV, and cultivating a sense of hope among AYAHIV. Successful prototypes included a media campaign to reduce HIV stigma and increase medical literacy; a toolkit to help providers communicate and address the unique needs of AYAHIV clients; peer-support groups to improve medical literacy, empower youth, and provide positive role models for people living with HIV; support groups for parents/caregivers; and discreet pill containers to promote adherence outside the home. In the next phase, the effectiveness of CombinaADO on retention in care, ART adherence, and viral suppression will be evaluated using a cluster-randomized control trial.We demonstrate the utility of using HCD to cocreate a multicomponent intervention to retain AYAHIV in care. We also discuss how the HCD methodology enriches participatory methods and community engagement. This is then illustrated by the youth-driven intervention development of CombinADO by fostering youth empowerment, addressing power imbalances between youth and adult stakeholders, and ensuring that language and content remain adolescent friendly.
(© Mukherjee et al.)

Background: Latinx family caregivers of individuals with dementia face many barriers to caregiver support access. Interventions to alleviate these barriers are urgently needed.
Objective: This study aimed to describe the development of CuidaTEXT, a tailored SMS text messaging intervention to support Latinx family caregivers of individuals with dementia.
Methods: CuidaTEXT is informed by the stress process framework and social cognitive theory. We developed and refined CuidaTEXT using a mixed methods approach that included thematic analysis and descriptive statistics. We followed 6 user-centered design stages, namely, the selection of design principles, software vendor collaboration, evidence-based foundation, caregiver and research and clinical advisory board guidance, sketching and prototyping, and usability testing of the prototype of CuidaTEXT among 5 Latinx caregivers.
Results: CuidaTEXT is a bilingual 6-month-long SMS text messaging-based intervention tailored to caregiver needs that includes 1-3 daily automatic messages (n=244) about logistics, dementia education, self-care, social support, end of life, care of the person with dementia, behavioral symptoms, and problem-solving strategies; 783 keyword-driven text messages for further help with the aforementioned topics; live chat interaction with a coach for further help; and a 19-page reference booklet summarizing the purpose and functions of the intervention. The 5 Latinx caregivers who used the prototype of CuidaTEXT scored an average of 97 out of 100 on the System Usability Scale.
Conclusions: CuidaTEXT's prototype demonstrated high usability among Latinx caregivers. CuidaTEXT's feasibility is ready to be tested.
(©Jaime Perales-Puchalt, Mariola Acosta-Rullán, Mariana Ramírez-Mantilla, Paul Espinoza-Kissell, Eric Vidoni, Michelle Niedens, Edward Ellerbeck, Ladson Hinton, Linda Loera, A Susana Ramírez, Esther Lara, Amber Watts, Kristine Williams, Jason Resendez, Jeffrey Burns. Originally published in JMIR Aging (https://aging.jmir.org), 28.04.2022.)

Drug Liberation, Humans, Pharmaceutical Preparations, Drug Delivery Systems methods, and Printing, Three-Dimensional

Novel additive manufacturing (AM) techniques and particularly 3D printing (3DP) have achieved a decade of success in pharmaceutical and biomedical fields. Highly innovative personalized therapeutical solutions may be designed and manufactured through a layer-by-layer approach starting from a digital model realized according to the needs of a specific patient or a patient group. The combination of patient-tailored drug dose, dosage, or diagnostic form (shape and size) and drug release adjustment has the potential to ensure the optimal patient therapy. Among the different 3D printing techniques, extrusion-based technologies, such as fused filament fabrication (FFF) and semi solid extrusion (SSE), are the most investigated for their high versatility, precision, feasibility, and cheapness. This review provides an overview on different 3DP techniques to produce personalized drug delivery systems and medical devices, highlighting, for each method, the critical printing process parameters, the main starting materials, as well as advantages and limitations. Furthermore, the recent developments of fused filament fabrication and semi solid extrusion 3DP are discussed. In this regard, the current state of the art, based on a detailed literature survey of the different 3D products printed via extrusion-based techniques, envisioning future directions in the clinical applications and diffusion of such systems, is summarized.

New fabrication approaches for mechanically flexible implants hold the key to advancing the applications of neuroengineering in fundamental neuroscience and clinic. By combining the high precision of thin film microfabrication with the versatility of additive manufacturing, we demonstrate a straight-forward approach for the prototyping of intracranial implants with electrode arrays and microfluidic channels. We show that the implant can modulate neuronal activity in the hippocampus through localized drug delivery, while simultaneously recording brain activity by its electrodes. Moreover, good implant stability and minimal tissue response are seen one-week post-implantation. Our work shows the potential of hybrid fabrication combining different manufacturing techniques in neurotechnology and paves the way for a new approach to the development of multimodal implants.

Problem: The extent of medical student unwellness is well-documented. Learner distress may impact patient care, workforce adequacy, and learners' performance and personal health. The authors describe the philosophy, structure, and content of the novel REACH (Recognize, Empathize, Allow, Care, Hold each other up) curriculum and provide a preliminary evaluation.
Approach: The REACH curriculum is a mandatory, longitudinal well-being curriculum for first- and second-year medical students at the Medical College of Wisconsin designed to prepare them for the emotional life of being a physician. The curriculum uses a framework, core concepts, and skills from the field of trauma stewardship. It builds on effective medical student well-being interventions (e.g., mindfulness-based training) and the sharing of personal stories by instructors during didactic and small-group sessions that are integrated into the regular MCW curriculum. During the first 2 years of implementation (2018-2019 and 2019-2020), the curriculum was evaluated using mid- and post-curriculum student surveys.
Outcomes: Over 700 students have completed the REACH curriculum as of March 2022. Overall, most students who responded to the surveys in 2018-2020 reported that they felt the REACH curriculum material was important, that the curriculum met their expectations for a quality medical school course, and that they would recommend other schools incorporate a similar curriculum. Respondents to the 2019-2020 post-curriculum survey indicated the REACH curriculum helped them develop self-care (84% [85/101]), mindfulness (76% [76/101]), and help-seeking (71% [72/101]) skills.
Next Steps: The initial outcomes show that integrating a mandatory well-being curriculum is feasible and acceptable to medical students. The authors plan to examine the relationships between student-reported well-being metrics, academic and clinical performance data, and professional identity formation. They are also prototyping electronic dashboards that will allow students to interact with their well-being data to promote timely help-seeking and behavior change.
(Copyright © 2022 by the Association of American Medical Colleges.)

Flow chemistry offers a solution for replacing batch methods in chemical preparation where intermediates or products may pose toxicity or instability hazards. Ozonolysis offers an ideal opportunity for flow chemistry solutions, but multiple barriers to entry exist for use of these methods, including equipment cost and performance optimization. To address these challenges, we developed a programmable DIY syringe pump system to use for a continuous flow multireactor process using 3D-printed parts, off-the-shelf stepper motors, and an Arduino microcontroller. Reaction kinetics of ozonide formation informed the use of an integrated batch-flow approach, where ozone addition to an olefin was timed to coincide with fluid movement of a single-syringe pump, followed by downstream Pinnick oxidation and reductive quench in flow. The system was demonstrated by continuous preparation of azelaic acid from ozonolysis of palmitoleic acid, a process limited to low production volumes via batch chemistry. High total production of azelaic acid with 80% yield was obtained from an algae oil sourced unsaturated fatty acid: a product with important applications in medicine, cosmetics, and polymers. This low-cost, scalable approach offers the potential for rapid prototyping and distributed chemical production.
(© 2022 The Authors. Published by American Chemical Society.)

Electric Conductivity, Electrodes, Thermodynamics, Electrolytes, and Printing, Three-Dimensional

The electric conductivity is one the most routinely inspected characteristics of aqueous media, being employed in monitoring drinking water quality and determining thermodynamic properties of electrolytes. In this work, we utilize fused deposition modelling 3D printing (3DP) to manufacture a platform composed of supporting cells and sensing electrodes for electric conductivity measurements of aqueous solutions. For the first time, the electric conductivity of liquid electrolytes is sensed by 3DP electrodes, employing a direct electrode/electrolyte contact. Conductivity measurements performed in the presented 3DP platform are controlled by an electronic circuitry developed employing a programmable system on chip prototyping kit. The entire conductometric setup was validated employing commercial conductance standards as well as in-lab prepared aqueous solutions of potassium chloride and formic and acetic acid as representatives of strong and weak electrolytes. Conductivity measurements enabled the correct determination of limiting molar conductivity (for potassium chloride) and dissociation constants (for the two weak acids). Finally, the functionality of the presented platform was confirmed by measuring conductivity of various bottled water samples. Results obtained in this work pave the wave for further development and applications of conductometers based on 3DP electrodes and cells.
(Copyright © 2022 Elsevier B.V. All rights reserved.)

Molecular nanofabrication with a scanning probe microscope (SPM) is a promising route toward the prototyping of metastable functional molecular structures and devices which do not form spontaneously. The aspect of mechanical stability is crucial for such structures, especially if they extend into the third dimension vertical to the surface. A prominent example is freestanding molecules fabricated on a metal which can function as field emitters or electric field sensors. Improving the stability of such molecular configurations is an optimization task involving many degrees of freedom and therefore best tackled by computational nanostructure design. Here, we use density functional theory to study 3,4,9,10-perylene-tetracarboxylic dianhydride (PTCDA) standing on the Ag(111) surface as well as on the tip of a scanning probe microscope. We cast our results into a simple set of design principles for such metastable structures, the validity of which we subsequently demonstrate in two computational case studies. Our work proves the capabilities of computational nanostructure design in the field of metastable molecular structures and offers the intuition needed to fabricate new devices without tedious trial and error.
(© 2022 The Authors. Published by American Chemical Society.)

Background: Augmented reality (AR) and brain-computer interface (BCI) are promising technologies that have a tremendous potential to revolutionize health care. While there has been a growing interest in these technologies for medical applications in the recent years, the combined use of AR and BCI remains a fairly unexplored area that offers significant opportunities for improving health care professional education and clinical practice. This paper describes a recent study to explore the integration of AR and BCI technologies for health care applications.
Objective: The described effort aims to advance an understanding of how AR and BCI technologies can effectively work together to transform modern health care practice by providing new mechanisms to improve patient and provider learning, communication, and shared decision-making.
Methods: The study methods included an environmental scan of AR and BCI technologies currently used in health care, a use case analysis for a combined AR-BCI capability, and development of an integrated AR-BCI prototype solution for health care applications.
Results: The study resulted in a novel interface technology solution that enables interoperability between consumer-grade wearable AR and BCI devices and provides the users with an ability to control digital objects in augmented reality using neural commands. The article discusses this novel solution within the context of practical digital health use cases developed during the course of the study where the combined AR and BCI technologies are anticipated to produce the most impact.
Conclusions: As one of the pioneering efforts in the area of AR and BCI integration, the study presents a practical implementation pathway for AR-BCI integration and provides directions for future research and innovation in this area.
(©Anya Andrews. Originally published in JMIR Formative Research (https://formative.jmir.org), 21.04.2022.)

Animals, Bone Regeneration, Humans, Porosity, Printing, Three-Dimensional, Rats, Weight-Bearing, X-Ray Microtomography, Durapatite, and Tissue Scaffolds

3D porous hydroxyapatite (HAP) scaffolds produced by conventional foaming processes have limited control over the scaffold's pore size, geometry, and pore interconnectivity. In addition, random internal pore architecture often results in limited clinical success. Imitating the intricate 3D architecture and the functional dynamics of skeletal deformations is a difficult task, highlighting the necessity for a custom-made, on-demand tissue replacement, for which 3D printing is a potential solution. To combat these problems, here we report the ability of 3D printed HAP scaffolds for in vivo bone regeneration in a rat tibial defect model. Rapid prototyping using the direct-write technique to fabricate 25 mm 2 HAP scaffolds were employed for precise control over geometry (both external and internal) and scaffold chemistry. Bone ingrowth was determined using histomorphometry and a novel micro-computed tomography (micro-CT) image analysis. Substantial bone ingrowth was observed in implants that filled the defect site. Further validating this quantitatively by micro-CT, the Bone mineral density (BMD) of the implant at the defect site was 1024 mgHA ccm -1 , which was approximately 61.5% more than the BMD found with the sham control at the defect site. In addition, no evident immunoinflammatory response was observed in the hematoxylin and eosin micrographs. Interestingly, the present study showed a positive correlation with the outcomes obtained in our previous in vitro study. Overall, the results suggest that 3D printed HAP scaffolds developed in this study offer a suitable matrix for rendering patient-specific and defect-specific bone formation and warrant further testing for clinical application.
(© 2022 IOP Publishing Ltd.)

Direct digital manufacturing consists of a set of techniques that enable products to be fabricated directly from their digital definition, without the use of complex tooling or moulds. This manufacturing approach streamlines prototyping and small-scale production, as well as the mass customization of parts with complex designs immediately fixed before fabrication. With broad applicability, there are clearly opportunities in the field of medical devices for its use. However, many of the developments of direct digital manufacturing focus on simply specifying the shape or the form of the product, and this limited scope throws away many of the particular advantages of direct digital manufacturing. This work is focused on remedying this situation so that the digital specification of the fabricated product includes the properties as well as the form of the product. We use in situ time-resolving small-angle X-ray scattering measurements performed at the ALBA Synchrotron Light Source in Barcelona to evaluate the control that can be exerted on the morphology of a semi-crystalline polymer during extruder-based 3D printing. We use this as a methodology for printing the patterns of the morphology of the polymer to realise the patterns of properties of the polymeric material, specifically the modulus of the polymer. We give an example of products produced in this manner that contain spatial variation in their properties.

Integrated optics, having the unique properties of small size, low loss, high integration, and high scalability, is attracting considerable attention and has found many applications in optical communications, fulfilling the requirements for the ever-growing information rate and complexity in modern optical communication systems. Femtosecond laser fabrication is an acknowledged technique for producing integrated photonic devices with unique features, such as three-dimensional fabrication geometry, rapid prototyping, and single-step fabrication. Thus, plenty of femtosecond laser-fabricated on-chip devices have been manufactured to realize various optical communication functions, such as laser generation, laser amplification, laser modulation, frequency conversion, multi-dimensional multiplexing, and photonic wire bonding. In this paper, we review some of the most relevant research progress in femtosecond laser-fabricated photonic chips for optical communications, which may break new ground in this area. First, the basic principle of femtosecond laser fabrication and different types of laser-inscribed waveguides are briefly introduced. The devices are organized into two categories: active devices and passive devices. In the former category, waveguide lasers, amplifiers, electric-optic modulators, and frequency converters are reviewed, while in the latter, polarization multiplexers, mode multiplexers, and fan-in/fan-out devices are discussed. Later, photonic wire bonding is also introduced. Finally, conclusions and prospects in this field are also discussed.

Background: The unique features of smartphones have extended their use in different fields, especially in the health care domain. These features offer new opportunities to support patients with chronic conditions by providing them with information, education, and self-management skills. We developed a digital self-management system to support children with cancer and their caregivers in Iran (low- and middle-income country).
Objective: This study is aimed at the development and preliminary evaluation of a cancer self-management system (CanSelfMan) tailored to the needs of children with cancer and their parents or caregivers.
Methods: This study was conducted in collaboration with a multidisciplinary team between January and February 2020 at MAHAK's Pediatric Cancer Treatment and Research Center. We developed a self-management system in six stages: requirement analysis, conformity assessment, preparation of educational content, app prototyping, preliminary evaluation, and developing the final version.
Results: A total of 35 people (n=24, 69% parents and n=11, 31% children) volunteered to participate in the study. However, only 63% (15/24) of parents and 73% (8/11) of children were eligible to participate. By adopting a user-centered design approach, we developed a mobile app, CanSelfMan, that includes five main modules (knowledge base, self-management tips, self-assessment report, ask a question, and reminders) that provide access to reliable information about acute lymphocytic leukemia and the self-management skills required for side effect measurement and reporting. A web-based dashboard was also developed for oncologists and included a dashboard to monitor users' symptoms and answer their questions.
Conclusions: The CanSelfMan app can support these groups by providing access to reliable information about cancer, facilitating communication between children or parents and health care providers, and helping promote medication adherence through a reminder function. The active participation of the target group can help identify their needs. Therefore, through the involvement of stakeholders such as patients, caregivers, and oncologists in the design process, we improved usability and ensured that the final product was useful. This app is now ready to proceed with feasibility studies.
(©Hamed Mehdizadeh, Farkhondeh Asadi, Hassan Emami, Azim Mehrvar, Eslam Nazemi. Originally published in JMIR Formative Research (https://formative.jmir.org), 15.04.2022.)

In an increasing effort to address the environmental challenges caused by the currently linear economic paradigm of "produce, use, and discard", the construction industry has been shifting towards a more circular model. A circular economy requires closing of the loops, where the end-of-life of a building is considered more carefully, and waste is used as a resource. In comparison to traditional building materials such as timber, steel and concrete, mycelium-based materials are renewable alternatives that use organic agricultural and industrial waste as a key ingredient for production, and do not rely on mass extraction or exploitation of valuable finite or non-finite resources. Mycelium-based materials have shown their potential as a more circular and economically competitive alternative to conventional synthetic materials in numerous industries ranging from packaging, electronic prototyping, furniture, fashion to architecture. However, application of mycelium-based materials in the construction industry has been limited to small-scale prototypes and architectural installations due to low mechanical properties, lack of standardisation in production methods and material characterisation. This paper aims to review the current state of the art in research and applications of mycelium-based materials across disciplines, with a particular focus on digital methods of fabrication, production, and design. The information gathered from this review will be synthesised to identify key challenges in scaling up applications of mycelium-based materials as load-bearing structural elements in architecture and suggest opportunities and directions for future research.

Reproducibility of Results and Deep Learning

Focused ion beam (FIB) milling is an important rapid prototyping tool for micro- and nanofabrication and device and materials characterization. It allows for the manufacturing of arbitrary structures in a wide variety of materials, but establishing the process parameters for a given task is a multidimensional optimization challenge, usually addressed through time-consuming, iterative trial-and-error. Here, we show that deep learning from prior experience of manufacturing can predict the postfabrication appearance of structures manufactured by focused ion beam (FIB) milling with >96% accuracy over a range of ion beam parameters, taking account of instrument- and target-specific artifacts. With predictions taking only a few milliseconds, the methodology may be deployed in near real time to expedite optimization and improve reproducibility in FIB processing.

Adhesives, Gelatin pharmacology, Humans, Tissue Scaffolds, Corneal Perforation, Fibroins pharmacology, Tissue Adhesives pharmacology, and Tissue Adhesives therapeutic use

Corneal defects are associated with corneal tissue engineering in terms of vision loss. The treatment of corneal defects is an important clinical challenge due to a uniform corneal thickness and the apparent lack of regenerative ability. In this work, we synthesized a biocompatible and photocrosslinkable ocular tissue adhesive composite hydrogel prepared by using methacrylated gelatin (GelMA), which is called the most favorable derivative of gelatin used as a tissue adhesive, silk fibroin (SF), and GelMA/SF (GS) with high adhesion behaviours for use in corneal injuries. The adhesion behaviours of the materials prepared in the presence of silk fibroin were improved. Importantly, the effect of different UV curing times on the adhesion properties of the prepared materials was also investigated. The prepared GS tissue adhesives showed high physiological adhesion. GS can be modulated to increase its adhesive strength up to 3 times compared to G. GS was also found to be biocompatible and have a high healing potential. In addition, the obtained transmission value of GS is also close to that of the human cornea. GS supported cellular adhesion and proliferation. The burst pressure strength for fresh cornea of the GS-60s sealants (144.5 ± 13 kPa) was determined to be higher than that of the G-60s sealants (52.6 ± 33.5 kPa).

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

Goal: Advances in computational models of biological systems and artificial neural networks enable rapid virtual prototyping of neuroprosthetics, accelerating innovation in the field. Here, we present an end-to-end computational model for predicting speech perception with cochlear implants (CI), the most widely-used neuroprosthetic.
Methods: The model integrates CI signal processing, a finite element model of the electrically-stimulated cochlea, and an auditory nerve model to predict neural responses to speech stimuli. An automatic speech recognition neural network is then used to extract phoneme-level speech perception from these neural response patterns.
Results: Compared to human CI listener data, the model predicts similar patterns of speech perception and misperception, captures between-phoneme differences in perceptibility, and replicates effects of stimulation parameters and noise on speech recognition. Information transmission analysis at different stages along the CI processing chain indicates that the bottleneck of information flow occurs at the electrode-neural interface, corroborating studies in CI listeners.
Conclusion: An end-to-end model of CI speech perception replicated phoneme-level CI speech perception patterns, and was used to quantify information degradation through the CI processing chain.
Significance: This type of model shows great promise for developing and optimizing new and existing neuroprosthetics.

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

Due to economic, cultural, environmental, and social factors, the prevalence of maxillofacial bone disorders varies in different parts of the world. The present meta-analysis was conducted to assess the efficacy and safety of different type of stem cells-based scaffolds and their construction methods in maxillofacial bone disorders. We searched major indexing databases, including PubMed/Medline, ISI Web of Science, Scopus, Embase, and Cochrane Central without any language, study region, or type restrictions. A systematic search of articles published up to July 2021 was done. Of the 428 studies found through initial searches, 36 met the inclusion criteria. After applying the exclusion criteria, the main properties of 32 articles on 643 animals and 4 experimental studies on 52 patients (age range from 43 to 74 years) included in this meta-analysis. Our pooled analysis showed that stem cells-based scaffolds significantly improved the bone regeneration and formation in maxillofacial bone disorders (Prevalence: 0.54; 95% CI: 0.43, 0.64, P < 00001, I 2  = 90 2). According to the results of these studies, in most studies, bone marrow-derived mesenchymal stem cells (BMSCs) have been used to regenerate bone, and these cells are still the gold standard in bone tissue engineering, a growth factor that is one of the three sides of the tissue engineering triangle. Bone morphogenetic proteins (BMP) especially BMP2 and platelet-rich plasma (PRP) are the most widely used growth factor and scaffold respectively. Platelet-rich plasma (PRP) is used as a scaffold and since it contains proteins, it also used as a growth factor and can be a stimulant of ossification. It seems that the future perspective of bone tissue engineering is to use the prototyping rapid method to build a composite and patient-specific scaffold from CT and MRI images, along with genetically modified stem cells.
(© 2022. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Objective. To describe and evaluate how a design thinking approach aided the creation of the 2021 American Association of Colleges of Pharmacy (AACP) Teacher's 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 Teacher's 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.
(© 2022 American Association of Colleges of Pharmacy.)

Catalysis, Metals, Serine Endopeptidases, Synthetic Biology, Protein Engineering, and Proteins

Dynamic control over protein function is a central challenge in synthetic biology. To address this challenge, we describe the development of an integrated computational and experimental workflow to incorporate a metal-responsive chemical switch into proteins. Pairs of bipyridinylalanine (BpyAla) residues are genetically encoded into two structurally distinct enzymes, a serine protease and firefly luciferase, so that metal coordination biases the conformations of these enzymes, leading to reversible control of activity. Computational analysis and molecular dynamics simulations are used to rationally guide BpyAla placement, significantly reducing experimental workload, and cell-free protein synthesis coupled with high-throughput experimentation enable rapid prototyping of variants. Ultimately, this strategy yields enzymes with a robust 20-fold dynamic range in response to divalent metal salts over 24 on/off switches, demonstrating the potential of this approach. We envision that this strategy of genetically encoding chemical switches into enzymes will complement other protein engineering and synthetic biology efforts, enabling new opportunities for applications where precise regulation of protein function is critical.
(© 2022. The Author(s).)

Dopamine, Dopamine Plasma Membrane Transport Proteins, Female, Humans, Exosomes, Mesenchymal Stem Cells, and Wharton Jelly

Exosomes between 40 and 200 nm in size constitute the smallest subgroup of extracellular vesicles. These bioactive vesicles secreted by cells play an active role in intercellular cargo and communication. Exosomes are mostly found in body fluids such as plasma, cerebrospinal fluid, urine, saliva, amniotic fluid, colostrum, breast milk, joint fluid, semen, and pleural acid. Considering the size of exosomes, it is thought that they may play an important role in central nervous system diseases because they can pass through the blood-brain barrier (BBB). Hence, this study aimed to develop an exosome-based nanocarrier system by encapsulating dopamine into exosomes isolated from Wharton's jelly mesenchymal stem cells (WJ-MSCs). Exosomes that passed the characterization process were incubated with dopamine. The dopamine-loaded exosomes were recharacterized at the end of incubation. Dopamine-loaded exosomes were investigated in drug release and cytotoxicity assays. The results showed that dopamine could be successfully encapsulated within the exosomes and that the dopamine-loaded exosomes did not affect fibroblast viability.

Chromatography, Liquid, Printing, Three-Dimensional, Solid Phase Extraction, Diclofenac, and Waste Water

This article reports current research efforts towards designing bespoke microscale extraction approaches exploiting the versatility of 3D printing for fast prototyping of novel geometries of sorptive devices. This is demonstrated via the so-called 3D printed spinning cup-based platform for immunoextraction of emerging contaminants using diclofenac as a model analyte. A new format of rotating cylindrical scaffold (containing a semispherical upper cavity) with enhanced coverage of biorecognition elements, and providing elevated enhancement factors with no need of eluate processing as compared with other microextraction stirring units is proposed. Two distinct synthetic routes capitalized upon modification of the acrylate surface of stereolithographic 3D printed parts with hexamethylenediamine or branched polyethyleneimine chemistries were assayed for covalent binding of monoclonal diclofenac antibody.Under the optimized experimental conditions, a LOD of 108 ng L -1 diclofenac, dynamic linear range of 0.4-1,500 µg L -1 , and enrichment factors > 83 (for near-exhaustive extraction) were obtained using liquid chromatography coupled with UV-Vis detection. The feasibility of the antibody-laden device for handling of complex samples was demonstrated with the analysis of raw influent wastewaters with relative recoveries ranging from 102 to 109%. By exploiting stereolithographic 3D printing, up to 36 midget devices were fabricated in a single run with an estimated cost of mere 0.68 euros per 3D print and up to 16 €/device after the incorporation of the monoclonal antibody.
(© 2022. The Author(s).)

Emulsions, Oils, Water, Capillaries, and Lab-On-A-Chip Devices

Hypothesis: Double emulsions with many monodispersed internal droplets are required for the fabrication of multicompartment microcapsules and tissue-like synthetic materials. These double emulsions can also help to optically resolve different coalescence mechanisms contributing to double emulsion destabilization. Up to date microfluidic double emulsions are limited to either core-shell droplets or droplets with eight or less inner droplets. By applying a two-step jet break-up within one setup, double emulsion droplets filled with up to several hundred monodispersed inner droplets can be achieved.
Experiments: Modular interconnected CNC-milled Lego®-inspired blocks were used to create two separated droplet break-up points within coaxial glass capillaries. Inner droplets were formed by countercurrent flow focusing within a small inner capillary, while outer droplets were formed by co-flow in an outer capillary. The size of inner and outer droplets was independently controlled since the two droplet break-up processes were decoupled.
Findings: With the developed setup W/O/W and O/W/O double emulsions were produced with different surfactants, oils, and viscosity modifiers to encapsulate 25-400 inner droplets in each outer drop with a volume percentage of inner phase between 7% and 50%. From these emulsions monodispersed multicompartment microcapsules were obtained. The report offers insights on the relationship between the coalescence of internal droplets and their release.
(Copyright © 2021 Elsevier Inc. All rights reserved.)

Humans, Otolaryngology, and Printing, Three-Dimensional

Purpose: The progressive expansion of the technology that facilitates the development of three-dimensional (3D) printing within the field of otorhinolaryngology has opened up a new study front in medicine. The objective of this study is to systematically review scientific publications describing the development of 3D models having applications in otorhinolaryngology, with emphasis on subareas with a large number of publications, as well as the countries in which the publications are concentrated.
Methods: In this literature review, specific criteria were used to search for publications on 3D models. The review considered articles published in English on the development of 3D models to teach otorhinolaryngology. The studies with presurgical purposes or without validation of the task by surgeons were excluded from this review.
Results: This review considered 39 articles published in 10 countries between 2012 and 2021. The works published prior to 2012 were not considered as per the inclusion criteria for the research. Among the 39 simulators selected for review, otology models comprised a total of 15 publications (38%); they were followed by rhinology, with 12 (31%); laryngology, with 8 (21%); and head and neck surgery, with 4 publications (10%).
Conclusion: The use of 3D technology and printing is well established in the context of surgical education and simulation models. The importance of developing new technological tools to enhance 3D printing and the current limitations in obtaining appropriate animal and cadaver models signify the necessity of investing more in 3D models.
(© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Artificial Intelligence, Clinical Decision-Making, Humans, Pandemics, Retrospective Studies, SARS-CoV-2, and COVID-19 epidemiology

Background: The COVID-19 pandemic affected healthcare systems worldwide. Predictive models developed by Artificial Intelligence (AI) and based on timely, centralized and standardized real world patient data could improve management of COVID-19 to achieve better clinical outcomes. The objectives of this manuscript are to describe the structure and technologies used to construct a COVID-19 Data Mart architecture and to present how a large hospital has tackled the challenge of supporting daily management of COVID-19 pandemic emergency, by creating a strong retrospective knowledge base, a real time environment and integrated information dashboard for daily practice and early identification of critical condition at patient level. This framework is also used as an informative, continuously enriched data lake, which is a base for several on-going predictive studies.
Methods: The information technology framework for clinical practice and research was described. It was developed using SAS Institute software analytics tool and SAS® Vyia® environment and Open-Source environment R ® and Python ® for fast prototyping and modeling. The included variables and the source extraction procedures were presented.
Results: The Data Mart covers a retrospective cohort of 5528 patients with SARS-CoV-2 infection. People who died were older, had more comorbidities, reported more frequently dyspnea at onset, had higher d-dimer, C-reactive protein and urea nitrogen. The dashboard was developed to support the management of COVID-19 patients at three levels: hospital, single ward and individual care level.
Interpretation: The COVID-19 Data Mart based on integration of a large collection of clinical data and an AI-based integrated framework has been developed, based on a set of automated procedures for data mining and retrieval, transformation and integration, and has been embedded in the clinical practice to help managing daily care. Benefits from the availability of a Data Mart include the opportunity to build predictive models with a machine learning approach to identify undescribed clinical phenotypes and to foster hospital networks. A real-time updated dashboard built from the Data Mart may represent a valid tool for a better knowledge of epidemiological and clinical features of COVID-19, especially when multiple waves are observed, as well as for epidemic and pandemic events of the same nature (e. g. with critical clinical conditions leading to severe pulmonary inflammation). Therefore, we believe the approach presented in this paper may find several applications in comparable situations even at region or state levels. Finally, models predicting the course of future waves or new pandemics could largely benefit from network of DataMarts.
(Copyright © 2022. Published by Elsevier B.V.)

Acetabulum, Adult, Electromyography, Female, Hip Joint physiology, Humans, Male, Muscle, Skeletal physiology, Young Adult, Hip physiology, and Thigh physiology

A better understanding of deep hip muscle function is needed to establish whether retraining and strengthening these muscles is a worthwhile target for rehabilitation. This study aimed to determine the contribution of the deep hip muscles to the direction of hip loading in the acetabulum. Hip contact forces were calculated during walking and squatting for 12 participants (age: 24 ± 4 yrs, 4 females) using electromyography-informed neuromusculoskeletal modelling. Models were configured with different deep hip muscle activation levels: deep hip muscles (piriformis, obturator internus and externus, gemellus superior and inferior, and quadratus femoris) informed by intramuscular electromyography measurements (i.e., normal activation; assisted activation) and simulated with zero (no activation) or maximal (maximal activation) activation. The angle between the hip contact force and the vector from the femoral head to the acetabular center (hip contact force angle) was calculated for all configurations, where lower angles equated to hip loading directed towards the acetabular center. The position and spread of acetabular loading during both tasks were calculated for all configurations and compared using a within-participant analysis of variance via statistical parametric mapping (P < 0.05). Maximal activation resulted in lower hip contact force angles and more anterior-inferior oriented, albeit a slightly reduced, spread of acetabular loading compared to assisted activation and no activation. Results suggest that, if activated maximally, the deep hip muscles can change the direction of hip loading away from commonly damaged areas of acetabular cartilage. Targeted training of these muscles may be relevant for individuals with hip pathology who present with unfavorable regional loading and/or cartilage lesions.
(Copyright © 2022 Elsevier Ltd. All rights reserved.)

Clinical Competence, Humans, Learning, Printing, Three-Dimensional, Ophthalmology, and Students, Medical

Practical sessions facilitate teaching, critical thinking, and coping skills, especially among medical students and professionals. Currently, in ophthalmology, virtual and augmented reality are employed for surgical training by using three-dimensional (3D) eyeball models. These 3D models when printed can be used not only for surgical training but also in teaching ophthalmic residents and fellows for concept learning through tactile 3D puzzle assembly. 3D printing is perfectly suited for the creation of complex bespoke items in a cost-effective manner, making it ideal for rapid prototyping. Puzzle making, when combined with 3D printing can evolve into a different level of learning in the field of ophthalmology. Though various 3D eyeball models are currently available, complex structures such as the cerebral venous system and the circle of Willis have never been 3D printed and presented as 3D puzzles for assembling and learning. According to our knowledge, this concept of ophthalmic pedagogy has never been reported. In this manuscript, we discuss in detail the 3D models created by us (patent pending), for printing into multiple puzzle pieces for effective tactile learning by cognitive assembling.

Humans, Printing, Three-Dimensional, Retrospective Studies, Cleft Lip surgery, Cleft Palate surgery, and Dental Implants

Objective: To determine the current applications of 3-dimensional (3D) printing in the care of patients with cleft lip and palate. We also reviewed 3D printing limitations, financial analysis, and future implications.
Design: Retrospective systematic review.
Methods: Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were used by 3 independent reviewers. Articles were identified from Cochrane library, Ovid Medline, and Embase. Search terms included 3D printing, 3 dimensional printing, additive manufacturing, rapid prototyping, cleft lip, and cleft palate. Exclusion criteria included articles not in English, animal studies, reviews without original data, oral presentations, abstracts, opinion pieces, and articles without relevance to 3D printing or cleft lip and palate.
Main Outcome Measures: Primary outcome measure was the purpose of 3D printing in the care of patients with cleft lip and palate. Secondary outcome measures were cost analysis and clinical outcomes.
Results: Eight-four articles were identified, and 39 met inclusion/exclusion criteria. Eleven studies used 3D printing models for nasoalveolar molding. Patient-specific implants were developed via 3D printing in 6 articles. Surgical planning was conducted via 3D printing in 8 studies. Eight articles utilized 3D printing for anatomic models/educational purposes. 3-Dimensional printed models were used for surgical simulation/training in 6 articles. Bioprinting was utilized in 4 studies. Secondary outcome of cost was addressed in 8 articles.
Conclusion: 3-Dimensional printing for the care of patients with cleft lip and palate has several applications. Potential advantages of utilizing this technology are demonstrated; however, literature is largely descriptive in nature with few clinical outcome measures. Future direction should be aimed at standardized reporting to include clinical outcomes, cost, material, printing method, and results.

Computer Simulation, Finite Element Analysis, Models, Cardiovascular, Prosthesis Design, Aortic Valve surgery, and Heart Valve Prosthesis

The competing structural and hemodynamic considerations in valve design generally require a large amount of in vitro hydrodynamic and durability testing during development, often resulting in inefficient "trial-and-error" prototyping. While in silico modelling through finite element analysis (FEA) has been widely used to inform valve design by optimising structural performance, few studies have exploited the potential insight FEA could provide into critical hemodynamic performance characteristics of the valve. The objective of this study is to demonstrate the potential of FEA to predict the hydrodynamic performance of tri-leaflet aortic valve implants obtained during development through in vitro testing. Several variations of tri-leaflet aortic valves were designed and manufactured using a synthetic polymer and hydrodynamic testing carried out using a pulsatile flow rig according to ISO 5840, with bulk hydrodynamic parameters measured. In silico models were developed in tandem and suitable surrogate measures were investigated as predictors of the hydrodynamic parameters. Through regression analysis, the in silico parameters of leaflet coaptation area, geometric orifice area and opening pressure were found to be suitable indicators of experimental in vitro hydrodynamic parameters: regurgitant fraction, effective orifice area and transvalvular pressure drop performance, respectively.

Crown Lengthening, Humans, Printing, Three-Dimensional, Stereolithography, Computer-Aided Design, and Dental Implants

Progress with additive 3D printing is revolutionizing biomaterial manufacturing, including clinical dentistry and prosthodontics. Among the several 3D additive printing technologies, stereolithography is very popular as it utilizes light-activated resin for precise resolution. A simplified digital technique was used to fabricate two designs of a surgical guide for crown lengthening. Two cases are presented that utilized digital imaging and communications in medicine (DICOM) files obtained with computed tomography (CT) imaging and processed using four CAD software (Blue Sky Plan, Exocad, Meshmixer and 3D Slicer). The final models were converted to standard tessellation (STL) files and the guides were 3D printed with an additive stereolithography (SLA) printer. The first case was fabricated with a bone model from cone beam computed tomography (CBCT) data, and the second case was generated with intraoral and wax-up scans alone. Both methods appear to be equally effective compared to using a conventional method of guide frabication. However, proximal bone reduction was a concern with both designs. Digitally fabricated 3D printed surgical guide for crown lengthening has merit and a practical design is needed for future clinical validation.
(© 2021 by the American College of Prosthodontists.)

Animals, Ergonomics, Farmers, Feasibility Studies, Humans, Bivalvia, Low Back Pain therapy, Occupational Diseases, and Self-Management

Purpose: Participatory ergonomics engages workers in the development of strategies to reduce workplace-related pain, offering a flexible and practical option to create individualized context-specific strategies. This paper describes the outcomes of a feasibility study using a participatory approach for self-management of low back pain in clam farmers.
Methods: A within-subject time-control design with repeated baseline and post-intervention assessment was used. After refining individual and team-based strategies, stakeholder interviews, and rapid prototyping, workers selected three strategies to use for 8 weeks. Frequency and ease of use for strategies are described. Pre-post paired t-tests were used for analysis of pain-related disability, difficulty and pain with work tasks, pain-related fear, self-efficacy, and coping. Analysis of improvements exceeding published and individual variability was calculated.
Results: Participants chose both team and individual strategies, most using strategies 5 days a week >50% of the time. Significant improvements in pain-related disability, pain during specific tasks, pain-related anxiety, and coping were seen after 8 weeks of implementing strategies. No changes in task difficulty, fear, self-efficacy and average resting pain were reported. Pain improvements > MDC 95 were reported by 74% with 56-64% > personalized MDC 95 for lifting tasks.
Conclusions: Pain-related disability, work activity pain ratings and related pain anxiety and coping improved beyond individual variability in this feasibility study. Multiple strategies allowed workers to choose relevant self-management options. Introduction of work-related changes in the workplace, visual demonstration, review of team videos and reminders were helpful. Further studies of this approach are needed.

Purpose of Review: This narrative will focus on the adoption of design thinking to improve patient-centered care innovation in Orthopedics.
Recent Findings: The literature reveals a complete set of applications of the design thinking approach in the different stages of the patient experience throughout the health context; however, the papers identified focus on specific parts of the process, and there is no systemic analysis about the different aspects involved in each stage of the complete experience. This review presents a holistic analysis concerning the application of design thinking to the distinct phases of innovation development in orthopedics, from the identification of the specific initial challenges up to the introduction of technology-based artifacts, such as innovations in the musculoskeletal health market. Systematic description of design thinking application to orthopedics, including concepts, methods, tools, and implementation examples in the most relevant phases of the patient experience-clinical treatment, perioperative care, and rehabilitation.
(© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)