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1. Designing Programmable Ferromagnetic Soft Metastructures for Minimally Invasive Endovascular Therapy

   Zhuang, Ran ; Tian, Jiawei ; Tassiopoulos, Apostolos ; Sadasivan, Chander ; Gu, Xianfeng ; Chen, Shikui ( August 2023 , Proceedings of the International Design Engineering Technical Conferences & Computers & Information in Engineering Conference)

   Minimally invasive endovascular therapy (MIET) is an innovative technique that utilizes percutaneous access and transcatheter implantation of medical devices to treat vascular diseases. However, conventional devices often face limitations such as incomplete or suboptimal treatment, leading to issues like recanalization in brain aneurysms, endoleaks in aortic aneurysms, and paravalvular leaks in cardiac valves. In this study, we introduce a new metastructure design for MIET employing re-entrant honeycomb structures with negative Poisson's ratio (NPR), which are initially designed through topology optimization and subsequently mapped onto a cylindrical surface. Using ferromagnetic soft materials, we developed structures with adjustable mechanical properties called magnetically activated structures (MAS). These magnetically activated structures can change shape under noninvasive magnetic fields, letting them fit against blood vessel walls to fix leaks or movement issues. The soft ferromagnetic materials allow the stent design to be remotely controlled, changed, and rearranged using external magnetic fields. This offers accurate control over stent placement and positioning inside blood vessels. We performed magneto-mechanical simulations to evaluate the proposed design's performance. Experimental tests were conducted on prototype beams to assess their bending and torsional responses to external magnetic fields. The simulation results were compared with experimental data to determine the accuracy of the magneto-mechanical simulation model for ferromagnetic soft materials. After validating the model, it was used to analyze the deformation behavior of the plane matrix and cylindrical structure designs of the Negative Poisson's Ratio (NPR) metamaterial. The results indicate that the plane matrix NPR metamaterial design exhibits concurrent vertical and horizontal expansion when subjected to an external magnetic field. In contrast, the cylindrical structure demonstrates simultaneous axial and radial expansion under the same conditions. The preliminary findings demonstrate the considerable potential and practicality of the proposed methodology in the development of magnetically activated MIET devices, which offer biocompatibility, a diminished risk of adverse reactions, and enhanced therapeutic outcomes. Integrating ferromagnetic soft materials into mechanical metastructures unlocks promising opportunities for designing stents with adjustable mechanical properties, propelling the field towards more sophisticated minimally invasive vascular interventions. 

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2. 3D printing using powder melt extrusion

   https://doi.org/10.1016/j.addma.2019.100811  

   Boyle, B. M. ( August 2019 , Additive manufacturing)

   Additive manufacturing promises to revolutionize manufacturing industries. However, 3D printing of novel build materials is currently limited by constraints inherent to printer designs. In this work, a bench-top powder melt extrusion (PME) 3D printer head was designed and fabricated to print parts directly from powder-based materials rather than filament. The final design of the PME printer head evolved from the Rich Rap Universal Pellet Extruder (RRUPE) design and was realized through an iterative approach. The PME printer was made possible by modifications to the funnel shape, pressure applied to the extrudate by the auger, and hot end structure. Through comparison of parts printed with the PME printer with those from a commercially available fused filament fabrication (FFF) 3D printer using common thermoplastics poly(lactide) (PLA), high impact poly(styrene) (HIPS), and acrylonitrile butadiene styrene (ABS) powders (< 1 mm in diameter), evaluation of the printer performance was performed. For each build material, the PME printed objects show comparable viscoelastic properties by dynamic mechanical analysis (DMA) to those of the FFF objects. However, due to a significant difference in printer resolution between PME (X–Y resolution of 0.8 mm and a Z-layer height calibrated to 0.1 mm) and FFF (X–Y resolution of 0.4 mm and a Z-layer height of 0.18 mm), as well as, an inherently more inconsistent feed of build material for PME than FFF, the resulting print quality, determined by a dimensional analysis and surface roughness comparisons, of the PME printed objects was lower than that of the FFF printed parts based on the print layer uniformity and structure. Further, due to the poorer print resolution and inherent inconsistent build material feed of the PME, the bulk tensile strength and Young’s moduli of the objects printed by PME were lower and more inconsistent (49.2 ± 10.7 MPa and 1620 ± 375 MPa, respectively) than those of FFF printed objects (57.7 ± 2.31 MPa and 2160 ± 179 MPa, respectively). Nevertheless, PME print methods promise an opportunity to provide a platform on which it is possible to rapidly prototype a myriad of thermoplastic materials for 3D printing. 

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3. Pain and Laboratory Animals: Publication Practices for Better Data Reproducibility and Better Animal Welfare

   https://doi.org/10.1371/journal. pone.0155001  

   Larry Carbone, Jamie Austin ( May 2016 , PloS one)

   Scientists who perform major survival surgery on laboratory animals face a dual welfare and methodological challenge: how to choose surgical anesthetics and post-operative analgesics that will best control animal suffering, knowing that both pain and the drugs that manage pain can all affect research outcomes. Scientists who publish full descriptions of animal procedures allow critical and systematic reviews of data, demonstrate their adherence to animal welfare norms, and guide other scientists on how to conduct their own studies in the field. We investigated what information on animal pain management a reasonably diligent scientist might find in planning for a successful experiment. To explore how scientists in a range of fields describe their management of this ethical and methodological concern, we scored 400 scientific articles that included major animal survival surgeries as part of their experimental methods, for the completeness of information on anesthesia and analgesia. The 400 articles (250 accepted for publication pre-2011, and 150 in 2014–15, along with 174 articles they reference) included thoracotomies, craniotomies, gonadectomies, organ transplants, peripheral nerve injuries, spinal laminectomies and orthopedic procedures in dogs, primates, swine, mice, rats and other rodents. We scored articles for Publication Completeness (PC), which was any mention of use of anesthetics or analgesics; Analgesia Use (AU) which was any use of post-surgical analgesics, and Analgesia Completeness (a composite score comprising intra-operative analgesia, extended post-surgical analgesia, and use of multimodal analgesia). 338 of 400 articles were PC. 98 of these 338 were AU, with some mention of analgesia, while 240 of 338 mentioned anesthesia only but not postsurgical analgesia. Journals’ caliber, as measured by their 2013 Impact Factor, had no effect on PC or AU. We found no effect of whether a journal instructs authors to consult the ARRIVE publishing guidelines published in 2010 on PC or AC for the 150 mouse and rat articles in our 2014–15 dataset. None of the 302 articles that were silent about analgesic use included an explicit statement that analgesics were withheld, or a discussion of how pain management or untreated pain might affect results. We conclude that current scientific literature cannot be trusted to present full detail on use of animal anesthetics and analgesics. We report that publication guidelines focus more on other potential sources of bias in experimental results, under-appreciate the potential for pain and pain drugs to skew data, PLOS ONE | DOI:10.1371/journal.pone.0155001 May 12, 2016 1 / 24 a11111 OPEN ACCESS Citation: Carbone L, Austin J (2016) Pain and Laboratory Animals: Publication Practices for Better Data Reproducibility and Better Animal Welfare. PLoS ONE 11(5): e0155001. doi:10.1371/journal. pone.0155001 Editor: Chang-Qing Gao, Central South University, CHINA Received: December 29, 2015 Accepted: April 22, 2016 Published: May 12, 2016 Copyright: © 2016 Carbone, Austin. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the paper and its Supporting Information files. Authors may be contacted for further information. Funding: This study was funded by the United States National Science Foundation Division of Social and Economic Sciences. Award #1455838. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. and thus mostly treat pain management as solely an animal welfare concern, in the jurisdiction of animal care and use committees. At the same time, animal welfare regulations do not include guidance on publishing animal data, even though publication is an integral part of the cycle of research and can affect the welfare of animals in studies building on published work, leaving it to journals and authors to voluntarily decide what details of animal use to publish. We suggest that journals, scientists and animal welfare regulators should revise current guidelines and regulations, on treatment of pain and on transparent reporting of treatment of pain, to improve this dual welfare and data-quality deficiency. 

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4. Evaluating commercial thermoplastic materials in fused deposition modeling 3D printing for their compatibility with DNA storage and analysis by quantitative polymerase chain reaction

   https://doi.org/10.1039/D2AY00772J  

   Eitzmann, Derek R. ; Anderson, Jared L. ( July 2022 , Analytical Methods)

   Nucleic acids are ubiquitous in biological samples and can be sensitively detected using nucleic acid amplification assays. To achieve highly accurate and reliable results, nucleic acid isolation and purification is often required and can limit the accessibility of these assays. Encapsulation of these workflows onto a single device may be achieved through fabrication methodologies featuring commercial three-dimensional (3D) printers. This study aims to characterize fused deposition modeling (FDM) filaments based on their compatibility with nucleic acid storage using quantitative polymerase chain reaction (qPCR). To study the adsorption of nucleic acids, storage vessels were fabricated using six common thermoplastics including: polylactic acid (PLA), nylon, acrylonitrile butadiene styrene (ABS), co-polyester (CPE), polycarbonate (PC), and polypropylene (PP). DNA adsorption of a short 98 base pair and a longer 830 base pair fragment to the walls of the vessel was shown to vary significantly among the polymer materials as well as the color varieties of the same polymer. PLA storage vessels were found to adsorb the least amount of the 98 base pair DNA after 12 hours of storage in 2.5 M NaCl TE buffer whereas the ABS and PC vessels adsorbed up to 97.2 ± 0.2% and 97.5 ± 0.2%. DNA adsorption could be reduced by decreasing the layer height of the 3D printed object, thereby increasing the functionality of the ABS storage vessel. Nylon was found to desorb qPCR inhibiting components into the stored solution which led to erroneous DNA quantification data from qPCR analysis. 

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5. Design and validation of a synchrotron proton beam line for FLASH radiotherapy preclinical research experiments

   https://doi.org/10.1002/mp.15370  

   Titt, Uwe ; Yang, Ming ; Wang, Xiaochun ; Iga, Kiminori ; Fredette, Nathaniel ; Schueler, Emil ; Lin, Steven H. ; Zhu, X. Ron ; Sahoo, Narayan ; Koong, Albert C. ; et al ( December 2021 , Medical Physics)

   The main purpose of this work was to generate and validate the dosimetric accuracy of proton beams of dimensions that are appropriate for in vivo small animal and in vitro ultrahigh dose rate (FLASH) radiotherapy experiments using a synchrotron‐based treatment delivery system. This study was performed to enable future investigations of the relevance of a spread‐out Bragg peak (SOBP) under FLASH conditions.

   The spill characteristics of the small field fixed horizontal beam line were modified to deliver accelerated protons in times as short as 2 ms and to control the dose delivered. A Gaussian‐like transverse beam profile was transformed into a square uniform one at FLASH dose rates, while avoiding low‐dose regions, a crucial requirement to protect normal tissue during FLASH irradiation. Novel beam‐shaping devices were designed using Monte Carlo techniques to produce up to about 6 cm³of uniform dose in SOBPs while maximizing the dose rate. These included a scattering foil, a conical flattening filter to maximize the flux of protons into the region of interest, energy filters, range compensators, and collimators. The shapes, sizes, and positions of the components were varied to provide the required field sizes and SOBPs.

   The designed and fabricated devices were used to produce 10‐, 15‐, and 20‐mm diameter, circular field sizes and 10‐, 15‐, and 20‐mm SOBP modulation widths at uniform physical dose rates of up to 375 Gy/s at the center of the SOBP and a minimum dose rate of about 255 Gy/s at the entrance, respectively, in cylindrical volumes. The flatness of lateral dose profiles at the center could be adjusted to within ±1.5% at the center of the SOBP. Assessment of systematic uncertainties, such as impact of misalignments and positioning uncertainties, was performed using simulations, and the results were used to provide appropriate adjustments to ensure high‐accuracy FLASH beam delivery for both in vitro and in vivo preclinical experiments.

   It is feasible to use synchrotron‐generated proton beams of sufficient dimensions for FLASH radiobiology experiments. We expect to use the system we developed to acquire in vitro and in vivo small animal FLASH radiobiology data as a function of dose, dose rate, oxygen content, and linear energy transfer to help us understand the underlying mechanisms of the FLASH phenomenon.

    

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