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Introduction: Papillary urothelial carcinomas are currently graded as either low- or high-grade tumors based on World Health Organization (WHO) 2022 guidelines for genitourinary tumors. However, a minority of tumors are mixed-grade tumors, composed predominantly of low-grade cancer with a minor high-grade component. In the 2022 WHO these cancers are recognized as having outcomes comparable to low-grade cancers, although data to date has been limited., Methods: The pathology records of a large academic institution were searched for mixed-grade, non-muscle invasive papillary carcinomas of the bladder and ureter in order to characterize prognosis of these cancers., Results: Of 136 cancers, the majority (n = 104, 76.5%) were solitary, mixed-grade tumors, while 21 (15.4%) had a concurrent low-grade cancer and 11 (8.1%) had multiple mixed-grade tumors at the time of diagnosis. At follow-up (median 48.3 months, range = 1.3 months-18.1 years), 71 cancers recurred (52.2%): 52 (38.2%) as low- or mixed-grade cancers and 18 (13.2%) as high-grade cancers. There were no instances of stage-progression to >p T2., Conclusions: The clinical outcome of mixed-grade carcinomas was similar to what has been reported for low-grade carcinomas. Based on our results, and prior congruent studies of mixed-grade lesions, these lesions may be regarded as a distinct sub-category with a better prognosis than high-grade tumors., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Vitrimer is a new, exciting class of sustainable polymers with healing abilities due to their dynamic covalent adaptive networks. However, a limited choice of constituent molecules restricts their property space and potential applications. To overcome this challenge, an innovative approach coupling molecular dynamics (MD) simulations and a novel graph variational autoencoder (VAE) model for inverse design of vitrimer chemistries with desired glass transition temperature (T g ) is presented. The first diverse vitrimer dataset of one million chemistries is curated and T g for 8,424 of them is calculated by high-throughput MD simulations calibrated by a Gaussian process model. The proposed VAE employs dual graph encoders and a latent dimension overlapping scheme which allows for individual representation of multi-component vitrimers. High accuracy and efficiency of the framework are demonstrated by discovering novel vitrimers with desirable T g beyond the training regime. To validate the effectiveness of the framework in experiments, vitrimer chemistries are generated with a target T g = 323 K. By incorporating chemical intuition, a novel vitrimer with T g of 311-317 K is synthesized, experimentally demonstrating healability and flowability. The proposed framework offers an exciting tool for polymer chemists to design and synthesize novel, sustainable polymers for various applications., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Background: Children with cerebral palsy (CP) have an injury to the central nervous system around the time of birth that affects the development of the brain and spinal cord. This injury leads to changes in gait neuromechanics, including muscle activity and joint kinematics. Transcutaneous spinal cord stimulation (tSCS) is a novel neuromodulation technique that may improve movement and coordination in children with CP when paired with targeted physical therapy., Research Question: How does the combination of tSCS and short-burst interval locomotor treadmill training (SBLTT) affect individual gait neuromechanics in children with CP?, Methods: Four children with CP (4-13 years old), received 24 sessions each of SBLTT only and SBLTT with tSCS (tSCS+SBLTT). Clinical assessments of spasticity and passive range of motion (PROM), as well as biomechanical assessments of joint kinematics, musculotendon lengths, and muscle activity were recorded during overground, barefoot walking. Assessments were taken before and after each intervention, and 8-weeks later., Results: The combination of tSCS+SBLTT led to greater increases in hip and knee extension than SBLTT only for three participants. Three children also became more plantarflexed at the ankle during stance after tSCS+SBLTT compared to SBLTT only. While tSCS+SBLTT reduced spasticity, these changes were only weakly correlated with changes in musculotendon lengths during gait or PROM, with the largest correlation between change in gastrocnemius operating musculotendon length during fast walking and gastrocnemius spasticity (R 2 = 0.26) and change in plantarflexor PROM and gastrocnemius spasticity (R 2 = 0.23)., Significance: Children with CP used a more upright, less crouched posture during gait after tSCS+SBLTT. Large reductions in spasticity after tSCS+SBLTT were only weakly correlated with changes in kinematics and PROM. Understanding the mechanisms by which tSCS may affect gait for children with CP is critical to optimize and inform the use of tSCS for clinical care., Competing Interests: Declaration of Competing Interest Chet T. Moritz serves as a clinical advisor to the company SpineX, who provided the stimulator for the study. SpineX also licensed IP generated by the team at the University of Washington, Chet T. Moritz, Katherine M. Steele, Siddhi R. Shrivastav, and Charlotte R. DeVol., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Epithelial cells respond to infection with the intracellular bacterial pathogen Listeria monocytogenes by altering their mechanics to promote collective infected cell extrusion (CICE) and limit infection spread across cell monolayers. However, the underlying biochemical pathways remain elusive. Here, using in vitro (epithelial monolayers) and in vivo (zebrafish larvae) models of infection with L. monocytogenes or Shigella flexneri, we explored the role of extracellular-signal-regulated kinase (ERK) activity waves in coordinating the mechanical battle between infected and surrounder uninfected cells that leads to CICE. We discovered that when ERK waves are suppressed, cells fail to exhibit alterations in cell shape and kinematics associated with CICE and behave more like quiescent uninfected monolayers. In particular, uninfected cells surrounding infection foci are unable to polarize, reinforce their monolayer stresses, and promote CICE. Our findings reveal that crosstalk between ERK waves and cell mechanics is key to collective elimination of large domains of infected cells., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Ambulatory individuals with lower limb amputations often face challenges with body support, body propulsion, and balance control. Carrying an infant, toddler, backpack, or other load can exacerbate these challenges and highlights the importance of prescribing the most suitable prosthetic foot. The aim of this study was to examine the influence of five different prosthetic feet on walking performance during various load carriage conditions., Methods: Biomechanical data were collected from twelve participants wearing five different prosthetic feet (four passive, one powered) while walking with no added load and carrying a load of 13.6 kg in four different positions: posterior, anterior, prosthetic side, and intact side., Findings: Based on our study population, a powered-ankle-foot offers additional body support when a load is carried posteriorly. If additional forward propulsion is needed while carrying a load anteriorly, a heel wedge is better than a stiffer foot. For individuals who may need additional sagittal plane balance control, no study foot was advantageous regardless of how the load was carried. For those who need additional frontal plane balance control during posterior load carriage, a heel wedge is better than a stiffer or powered foot. Lastly, the standard-of-care, heel wedge, and dual keel feet provided more frontal plane balance control than a powered foot when a load was carried anteriorly., Interpretation: For individuals with lower limb amputation who carry loads, consideration of their preferred load carrying method may help select an appropriate prosthetic foot for body support, propulsion, and balance control., Competing Interests: Declaration of competing interest None., (Copyright © 2025. Published by Elsevier Ltd.)

Objective: To validate the use of neural radiance fields (NeRF), a state-of-the-art computer vision technique, for rapid, high-fidelity 3-dimensional (3D) reconstruction in endoscopic sinus surgery (ESS)., Study Design: An experimental cadaveric pilot study., Setting: Academic medical center., Methods: Complete bilateral endoscopic sinus surgery was performed on 3 cadaveric specimens, followed by postsurgical nasal endoscopy using a 0° rigid endoscope. NeRF was utilized to generate 3D reconstructions from the monocular endoscopic video feed. Reconstructions were calibrated, scaled, and then co-registered to postoperative computed tomography (CT) image sets to assess accuracy. Reconstruction error was determined by comparing ethmoid sinus measurements on NeRF reconstructions and CT image sets., Results: NeRF-based 3D scene reconstructions were successfully generated and co-registered to corresponding CT images for 5 out of 6 cadaveric nasal cavity sides. The mean reconstruction errors and standard error of the mean (SEM) for ethmoid length and height were 0.17 (SEM 0.59) and 0.70 (SEM 0.44) mm, respectively., Conclusion: NeRF demonstrates significant potential for dynamic, high-fidelity 3D surgical field reconstruction in ESS, offering submillimeter accuracy comparable to postoperative CT data in cadaveric specimens. This innovative approach may ultimately augment dynamic real-time intraoperative navigation through co-registration of the 3D reconstruction with preoperative imaging to potentially reduce the risk of injury to critical structures, optimize surgical completeness and, thereby, improve surgical outcomes. Further refinement and validation in live surgical settings are necessary to fully realize its clinical utility., (© 2025 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Background: Liver disease is a growing burden. Transplant organs are scarce. Extracorporeal liver support systems (ELSS) are a bridge to transplantation for eligible patients. For transplant-ineligible patients the objective becomes liver recovery., Methods: We review seven decades of non-cell-based ELSS research in humans. Where possible, we emphasize randomized controlled trials (RCTs). When RCTs are not available, we describe the available human clinical data., Results: There are three broad cell-free approaches to remove protein-bound toxins (PBTs) and treat liver failure. The first is a dialysate binder suspension. A material that binds the PBT (the binder) is added to the dialysate. Binders include albumin, charcoal, and polystyrene sulfonate sodium. The unbound fraction of the PBT crosses the dialyzer membrane along a chemical gradient and binds to the binder. The second approach is using grains of sorbent fixed in a plastic housing to remove PBTs. Toxin-laden blood or plasma flows directly through the column. Toxins are removed by binding to the sorbent. The third approach is exchanging toxin-laden blood, or fractions of blood, for a healthy donor blood product. Most systems lack widespread acceptance, but plasma exchange (PE) is recommended in many guidelines. The large donor plasma requirement of PE creates demand for systems to complement or replace it., Conclusions: Now that PE has become recommended in some, but not all, jurisdictions, we discuss the importance of reporting precise PE protocols and dose. Our work provides an overview of promising new systems and lessons from old technologies to enable ELSS improvement., (© 2024 International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Trigger valves are fundamental features in capillary-driven microfluidic systems that stop fluid at an abrupt geometric expansion and release fluid when there is flow in an orthogonal channel connected to the valve. The concept was originally demonstrated in closed-channel capillary circuits. We show here that trigger valves can be successfully implemented in open channels. We also show that a series of open-channel trigger valves can be placed alongside or opposite a main channel resulting in a layered capillary flow. We developed a closed form model for the dynamics of the flow at trigger valves based on the concept of average friction length and successfully validated the model against experiments. For the main channel, we discuss layered flow behavior in the light of the Taylor-Aris dispersion theory and in the channel turns by considering Dean theory of mixing. This work has potential applications in autonomous microfluidics systems for biosensing, at-home or point-of-care sample preparation devices, hydrogel patterning for 3D cell culture and organ-on-a-chip models., Competing Interests: Declarations. Competing interests: A.B.T. reports filing multiple patents through the University of Washington and A.B.T. received a gift to support research outside the submitted work from Ionis Pharmaceuticals. E.B. is an inventor on multiple patents filed by Tasso, Inc., the University of Washington, and the University of Wisconsin-Madison. T.M.N. has ownership in Tasso, Inc.; E.B. has ownership in Tasso, Inc., Salus Discovery, LLC, and Seabright, LLC and is employed by Tasso, Inc.; and A.B.T. has ownership in Seabright, LLC; however, this research is not related to these companies. The terms of this arrangement have been reviewed and approved by the University of Washington in accordance with its policies governing outside work and financial conflicts of interest in research. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024. The Author(s).)

Developmentally appropriate access to technology can support toddlers in learning and play. While touch screens are a popular interaction modality for children under the age of three, they may not be appropriate for all children or all tasks. We know comparatively little about how toddlers interact with joystick-based technology, and more fundamental research is required to understand joystick interactions at different ages and developmental stages. We quantified how 36 nondisabled toddlers used a joystick to play a cause-and-effect game on a computer. Children demonstrated a strong preference for moving the joystick forward first, regardless of the target direction. On average, the oldest children navigated the joystick to the target 5 seconds faster than the youngest children, and were nearly twice as efficient in their joystick path. These findings inform the design of assistive algorithms for joystick-enabled computer play and developmentally appropriate technologies for toddlers., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ingraham et al. 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.)

The results of a Phase 1 trial of autologous mitochondrial transplantation for the treatment of acute ischemic stroke during mechanical thrombectomy are presented. Standardized methods were used to isolate viable autologous mitochondria in the acute clinical setting, allowing for timely transplantation within the ischemic window. No significant adverse events were observed with the endovascular approach during reperfusion therapy. Safety outcomes in study participants were comparable to those of matched controls who did not undergo transplantation. This study represents the first use of mitochondrial transplantation in the human brain, highlighting specific logistical challenges related to the acute clinical setting, such as limited tissue samples and constrained time for isolation and transplantation. We also review the opportunities and challenges associated with further clinical translation of mitochondrial transplantation in the context of acute cerebral ischemia and beyond., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: MRL receives unrestricted educational grants from Medtronic and Stryker; consulting agreement with Aeaean Advisers, Metis Innovative, Genomadix, and AIDoc; equity interest in Proprio, Stroke Diagnostics, Apertur, Stereotaxis, Fluid Biomed, Synchron and Hyperion Surgical; editorial board of Journal of NeuroInterventional Surgery; Data safety monitoring board of Arsenal Medical. All other authors declare that they have no conflict of interest.

Purpose: Flow diverting stents (FDS) are used to treat cerebral aneurysms, by promoting thrombosis and occlusion of the aneurysm sac. However, retreatment is required in some cases, and the biologic basis behind treatment outcome is not known. The goal of this study was to understand how changes in hemodynamic flow after FDS placement affect aneurysmal endothelial cell (EC) activity., Methods: Three-dimensional models of patient-specific aneurysms were created to quantify the EC response to FDS placement. Computational fluid dynamic simulations were used to determine the hemodynamic impact of FDS. Two identical models were created for each patient; into one a FDS was inserted. Each model was then populated with human carotid ECs and subjected to patient-specific pulsatile flow for 24 h. ECs were isolated from aneurysm dome from each model and bulk RNA sequencing was performed., Results: Paired untreated and treated models were created for four patients. Aneurysm dome EC analysis revealed 366 (2.6%) significant gene changes between the untreated and FDS conditions, out of 13909 total expressed genes. Gene set enrichment analysis of the untreated models demonstrated enriched gene ontology terms related to cell adhesion, growth/tensile activity, cytoskeletal organization, and calcium ion binding. In the FDS models, enriched terms were related to cellular proliferation, ribosomal activity, RNA splicing, and protein folding., Conclusion: Treatment of cerebral aneurysms with FDS induces significant EC gene transcription changes related to aneurysm hemodynamics in patient-specific in vitro 3D-printed models subjected to pulsatile flow. Further investigation is needed into the relationship between transcriptional change and treatment outcome., Competing Interests: Declarations Conflict of interest Dr. Levitt is the recipient of educational grants from Stryker and Medtronic. He reports equity interest in Synchron, Stroke Diagnostics, Proprio, Hyperion Surgical, Fluid Biomed, and Apertur. He is an advisor for Metis Innovative, and is a consultant for Medtronic, Aeaean Advisors and Stereotaxis. He is on the editorial board of Journal of NeuroInterventional Surgery and the Data Safety Monitoring Board of Arsenal Medical., (© 2024. The Author(s) under exclusive licence to Biomedical Engineering Society.)

Quantifying individualized rehabilitation responses and optimizing therapy for each person is challenging. For interventions like treadmill training, there are multiple parameters, such as speed or incline, that can be adjusted throughout sessions. This study evaluates if causal modeling and Bayesian Additive Regression Trees (BART) can be used to accurately track the direct effects of treadmill training on gait. We developed a Directed Acyclic Graph (DAG) to specify the assumed relationship between training input parameters and spatiotemporal outcomes during Short Burst Locomotor Treadmill Training (SBLTT), a therapy designed specifically for children with cerebral palsy (CP). We evaluated outcomes after 24 sessions of SBLTT for simulated datasets of 150 virtual participants and experimental data from four children with CP, ages 4-13 years old. Individual BART models were created from treadmill data of each step. Simulated datasets demonstrated that BART could accurately identify specified responses to training, including strong correlations for step length progression (R 2  = 0.73) and plateaus (R 2  = 0.87). Model fit was stronger for participants with less step-to-step variability but did not impact model accuracy. For experimental data, participants' step lengths increased by 26 ± 13% after 24 sessions. Using BART to control for speed or incline, we found that step length increased for three participants (direct effect: 13.5 ± 4.5%), while one participant decreased step length (-11.6%). SBLTT had minimal effects on step length asymmetry and step width. Tools such as BART can leverage step-by-step data collected during training for researchers and clinicians to monitor progression, optimize rehabilitation protocols, and inform the causal mechanisms driving individual responses., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Individuals with transtibial amputation (TTA) experience altered gait mechanics, which are primarily attributed to the functional loss of the ankle plantarflexors. The plantarflexors contribute to body support and propulsion and play an important role in adapting to different load carriage conditions. However, how muscle function is altered across different prosthetic foot types and load carriage scenarios for individuals with TTA remains unclear. This study used musculoskeletal modeling and simulation of human movement in OpenSim to investigate the effects of a range of prosthetic feet and load conditions on individual muscle and prosthetic foot contributions to body support and propulsion. Twenty walking trials were collected from five individuals with TTA, consisting of five loading conditions (no-load; 30 lbs (13.6 kg) carried as a front-load, back-load, intact-side-load and residual-side-load) while wearing four prosthetic feet (their passive standard of care (SOC) foot, their SOC foot one category stiffer, their SOC foot with a heel stiffening wedge, and a dual-keel foot). Two participants also wore a powered ankle-foot prosthesis, thus completing an additional five trials each. The results indicated that the front-load condition may be more challenging because it required overall increased muscle contributions to body support and propulsion. However, the front- and residual-side-loads required reduced intact-side plantarflexor contributions to support and propulsion, and thus may be advantageous for individuals with plantarflexor weakness. Further, the large variability across contributions suggests that individuals with TTA may rely on a variety of compensatory mechanisms depending on the load condition and prosthetic foot used., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Maintaining adequate levels of antiretroviral (ARV) medications is crucial for the efficacy of HIV treatment and prevention regimens. Monitoring ARV levels can predict or prevent adverse health outcomes like treatment failure or drug resistance. However, conventional ARV measurement using liquid chromatography-tandem mass spectrometry (LC-MS/MS) is slow, expensive, and centralized delaying clinical and behavioral interventions. We previously developed a rapid enzymatic assay for measuring nucleotide reverse transcriptase inhibitors (NRTIs) - the backbone of HIV treatment and prevention regimens - based on the drugs' termination of DNA synthesis by HIV reverse transcriptase (RT) enzyme. Here, we expand our work to include non-nucleoside reverse transcriptase inhibitors (NNRTIs) - an ARV class used in established and emerging HIV treatment and prevention regimens. We demonstrate that the REverse Transcriptase ACTivity (REACT) assay can detect NNRTIs including medications used in oral and long-acting/extended-release HIV treatment and prevention. We demonstrate that REACT can measure NNRTIs spiked in either buffer or diluted plasma and that fluorescence can be measured on both a traditional plate reader and an inexpensive portable reader that can be deployed in point-of-care (POC) settings. REACT measured clinically relevant concentrations of five NNRTIs spiked in aqueous buffer. REACT measurements showed excellent agreement between the plate reader and the portable reader, with a high correlation in both aqueous buffer (Pearson's r = 0.9807, P < 0.0001) and diluted plasma (Pearson's r = 0.9681, P < 0.0001). REACT has the potential to provide rapid measurement of NNRTIs in POC settings and may help to improve HIV treatment and prevention outcomes., Competing Interests: Declarations. Conflict of interest: A.O. is an inventor on a patient filed (PCT/US2020/037609) based on related work on enzymatic assays for measuring reverse transcriptase inhibitors. Provisional patent applications have been filed on several components of the Harmony reader. N.P. and B.L. are inventors on two patent applications: PCT/US2021/041035 (pending international patent application) and 63/165,029 (pending U.S. provisional patent). N.P. and B.L. hold equity in a startup company that has licensed related technology and supports ongoing work in the B.L. laboratory at the University of Washington. B.L. serves as a scientific advisor for the company. The company played no role in the funding, study design, data analyses, or reporting of results for this study. C.B., M.A.S., J.T., C.C., S.G., and M.M.C. have no conflicts of interest to declare., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Stroke is a leading cause of death and disability worldwide. Atrial myopathy, including fibrosis, is associated with an increased risk of ischaemic stroke, but the mechanisms underlying this association are poorly understood. Fibrosis modifies myocardial structure, impairing electrical propagation and tissue biomechanics, and creating stagnant flow regions where clots could form. Fibrosis can be mapped non-invasively using late gadolinium enhancement magnetic resonance imaging (LGE-MRI). However, fibrosis maps are not currently incorporated into stroke risk calculations or computational electro-mechano-fluidic models. We present multiphysics simulations of left atrial (LA) myocardial motion and haemodynamics using patient-specific anatomies and fibrotic maps from LGE-MRI. We modify tissue stiffness and active tension generation in fibrotic regions and investigate how these changes affect LA flow for different fibrotic burdens. We find that fibrotic regions and, to a lesser extent, non-fibrotic regions experience reduced myocardial strain, resulting in decreased LA emptying fraction consistent with clinical observations. Both fibrotic tissue stiffening and hypocontractility independently reduce LA function, but, together, these two alterations cause more pronounced effects than either one alone. Fibrosis significantly alters flow patterns throughout the atrial chamber, and particularly, the filling and emptying jets of the left atrial appendage (LAA). The effects of fibrosis in LA flow are largely captured by the concomitant changes in LA emptying fraction except inside the LAA, where a multifactorial behaviour is observed. This work illustrates how high-fidelity, multiphysics models can be used to study thrombogenesis mechanisms in patient-specific anatomies, shedding light onto the links between atrial fibrosis and ischaemic stroke. KEY POINTS: Left atrial (LA) fibrosis is associated with arrhythmogenesis and increased risk of ischaemic stroke; its extent and pattern can be quantified on a patient-specific basis using late gadolinium enhancement magnetic resonance imaging. Current stroke risk prediction tools have limited personalization, and their accuracy could be improved by incorporating patient-specific information such as fibrotic maps and haemodynamic patterns. We present the first electro-mechano-fluidic multiphysics computational simulations of LA flow, including fibrosis and anatomies from medical imaging. Mechanical changes in fibrotic tissue impair global LA motion, decreasing LA and left atrial appendage (LAA) emptying fractions, especially in subjects with higher fibrosis burdens. Fibrotic-mediated LA motion impairment alters LA and LAA flow near the endocardium and the whole cavity, ultimately leading to more stagnant blood regions in the LAA., (© 2024 The Authors. The Journal of Physiology © 2024 The Physiological Society.)

Flexible thermoelectric devices (TEDs) exhibit adaptability to curved surfaces, holding significant potential for small-scale power generation and thermal management. However, they often compromise stretchability, energy conversion, or robustness, thus limiting their applications. Here, the implementation of 3D soft architectures, multifunctional composites, self-healing liquid metal conductors, and rigid semiconductors is introduced to overcome these challenges. These TEDs are extremely stretchable, functioning at strain levels as high as 230%. Their unique design, verified through multiphysics simulations, results in a considerably high power density of 115.4 µW cm⁻ 2 at a low-temperature gradient of 10 °C. This is achieved through 3D printing multifunctional elastomers and examining the effects of three distinct thermal insulation infill ratios (0%, 12%, and 100%) on thermoelectric energy conversion and structural integrity. The engineered structure is lighter and effectively maintains the temperature gradient across the thermoelectric semiconductors, thereby resulting in higher output voltage and improved heating and cooling performance. Furthermore, these thermoelectric generators show remarkable damage tolerance, remaining fully functional even after multiple punctures and 2000 stretching cycles at 50% strain. When integrated with a 3D-printed heatsink, they can power wearable sensors, charge batteries, and illuminate LEDs by scavenging body heat at room temperature, demonstrating their application as self-sustainable electronics., (© 2024 Wiley‐VCH GmbH.)

Carrying side loads often occurs during activities of daily living. As walking is most unstable mediolaterally, side load carriage may further compromise gait biomechanics, especially for transtibial amputees (TTAs). This study investigated the effects of side load carriage on gait kinetics during steady-state walking to determine which side, intact or prosthetic, TTAs should carry a load. Twelve unilateral TTAs wore a passive-elastic foot and carried a side load of 13.6 kg while walking at their self-selected speed. Kinetic metrics, including ground reaction force peaks and impulses, loading and unloading rates, and joint moments and powers, were analyzed. TTAs had smaller propulsive forces on their intact limb during the prosthetic side load condition. During the intact side load condition, they had smaller hip flexor moment in late stance and smaller knee flexor moment at the end of swing on their intact limb. They had higher hip and knee abductor moments on their intact limb and prosthetic limb in early and late stance during the contralateral side load condition. TTAs generated higher hip extensor power at weight acceptance during the ipsilateral side load. Significant interactions were observed in hip extensor power and abductor moment, suggesting strong associations between hip extensor power generation and the ipsilateral side load and between hip abductor moment and the contralateral side load. These mixed results demonstrate some kinetic changes due to side load carriage and suggest that the side TTAs should carry a load depends on the desired effects, primarily on their intact limb., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

Increasing utilization of weight-bearing computed tomography and fluoroscopy has driven the need for standardization of 3 dimensional (3D) measurements in the foot and ankle. These emerging imaging modalities are currently used to evaluate foot and ankle conditions including ankle osteoarthritis, progressive collapsing foot deformity, midfoot instability, and hallux valgus. This study aims first to provide a comprehensive review of clinical studies that have utilized these 3D methodologies. As a second goal, this study presents the methodological approach proposed by an international task force of experts toward addressing those concerns to provide validated guidelines for 3D static and dynamic measurements., Competing Interests: Disclosure Dr A. Burssens reports disclosures for CurveBeam. Dr C. de Cesar Netto reports disclosures for Paragon28, CurveBeam, Ossio, Medartis, Stryker, Tayco Brace, Zimmer, and Artelon. Dr Lintz reports disclosures for CurveBeam, Newclip Technics, and Paragon28., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The patient-specific shape of custom accommodative insoles for individuals with diabetes provides full foot-to-insole contact, offloading areas with high plantar pressures and reducing ulceration risk. To design the insole surface, plantar surface shape is captured, traditionally with a foam crush box impression or more recently with 3D scans of the foot. Beyond discrete measurements of the foot, the overall plantar surface shapes obtained from these different methods have yet to be compared, however, differences in the shapes captured by these methods may affect the insole's surface geometry design and subsequent performance., Methods: Plantar surface shapes of 12 individuals with diabetes were captured using a foam crush box, flatbed 3D foot scanner, and handheld 3D scanner. Foot length, width, arch height, and arch volume were measured from each shape-capture method and compared. Mesh-to-mesh distances between the foam crush box mesh and the direct scanning method meshes for each subject were calculated., Results: Foot length and width measured from the foam crush box scan were greater than the foot length measured from the flatbed scan and handheld scan. The flatbed scan also measured a length and width greater than the handheld scan. Arch heights and volumes from the flatbed scan were less than the heights calculated from the foam crush box and handheld scan. Mesh-to-mesh distances for the flatbed scan and areas of the foot not in contact with the scanner were inferior to the corresponding areas in the foam crush box impression. For the handheld scan, the lateral hindfoot and midfoot were superior, and the medial forefoot was inferior to the foam crush box impression., Conclusions: Different clinical methods used to capture foot shapes for the design of accommodative insoles may result in different plantar surface shape outputs and therefore impact custom accommodative insole design., (Published 2025. This article is a U.S. Government work and is in the public domain in the USA. Journal of Foot and Ankle Research published by John Wiley & Sons Australia, Ltd on behalf of Australian Podiatry Association and The Royal College of Podiatry.)

Background: There is growing interest in the use of biofeedback-augmented gait training in cerebral palsy (CP). Audiovisual, sensorimotor, and immersive biofeedback paradigms are commonly used to elicit short-term gait improvements; however, outcomes remain variable. Because biofeedback training requires that individuals have the capacity to both adapt their gait in response to feedback and retain improvements across sessions, changes in either capacity may affect outcomes. Yet, neither has been explored extensively in CP., Methods: In this study, we evaluated the extent to which adolescents with CP (7M/1F; 14 years (12.5,15.26)) could adapt gait and retain improvements across four, 20-minute sessions using combined audiovisual and sensorimotor biofeedback. Both systems were designed to target plantarflexor activity. Audiovisual biofeedback displayed real-time soleus activity and sensorimotor biofeedback was provided using a bilateral resistive ankle exoskeleton. We quantified the time-course of change in muscle activity within and across sessions and overground walking function before and after the four sessions., Results: All individuals were able to significantly increase soleus activity from baseline using multimodal biofeedback (p < 0.031) but demonstrated heterogeneous adaptation strategies. In-session soleus adaptation had a moderate positive correlation with short-term retention of the adapted gait patterns (0.40 ≤ ρ ≤ 0.81), but generally weak correlations with baseline walking function (GMFCS Level) and motor control complexity (ρ ≤ 0.43). The latter indicates that adaptation capacity may be a critical and unique metric underlying response to biofeedback. Notably, in-session gains did not correspond to significant improvements in overground walking function (p > 0.11)., Conclusions: This work suggests that individuals with CP have the capacity to adapt their gait using biofeedback, but responses are highly variable. Characterizing the factors driving adaptation to biofeedback may be a promising avenue to understand the heterogeneity of existing biofeedback training outcomes and inform future system optimization for integration into clinical care., Competing Interests: Dr. Zachary Lerner is a co-founder with shareholder interest in a start-up company that is seeking to commercialize the sensorimotor biofeedback system used in this study. There are no other conflicts of interest to disclose., (Copyright: © 2024 Spomer et al. 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.)

Quantitative phase imaging (QPI) recovers the exact wavefront of light from intensity measurements. Topographical and optical density maps of translucent microscopic bodies can be extracted from these quantified phase shifts. We demonstrate quantitative phase imaging at the tip of a coherent fiber bundle using chromatic aberrations inherent in a silicon nitride hyperboloid metalens. Our method leverages spectral multiplexing to recover phase from multiple defocus planes in a single capture using a color camera. Our 0.5 mm aperture metalens shows robust quantitative phase imaging capability with a 28 ∘ field of view and 0. 2 π phase resolution ( ~ 0. 1 λ in air) for experiments with an endoscopic fiber bundle. Since the spectral functionality is encoded directly in the imaging lens, the metalens acts both as a focusing element and a spectral filter. The use of a simple computational backend will enable real-time operation. Key limitations in the adoption of phase imaging methods for endoscopy such as multiple acquisition, interferometric alignment or mechanical scanning are completely mitigated in the reported metalens based QPI., (© 2024. The Author(s).)

Fracture site motion is thought to play an important role in the healing of complex fractures of the distal femur via mechanotransduction. Measuring this motion in vivo is challenging, and this has led researchers to turn to finite element modeling approaches to gain insights into the mechanical environment at the fracture site. Developing a systematic understanding of the effect of different model choices for distal femur fractures may allow more accurate prediction of fracture site motion from these types of simulations. In this study, we aim to assess the effect of four different modeling choices and parameters. We looked at the effect of using bone specific density distributions vs generic values, employing landmark-based geometry generation, varying fracture alignment within clinically relevant ranges, and determining whether direct apposition of the fracture to the plate was achieved. For validation, five cadaveric femurs had fractures created and repaired with plated constructs, and these were then loaded and fracture site motion was directly measured. We found that using landmark based bone geometry and patient-specific bone density distributions had a minimal effect on the overall model predictions. Changing the alignment, particularly into varus and procurvatum could have a large (>50%) effect on predicted shear motion, as could direct apposition of the bone to the plate. These findings demonstrate that modeling choices can play an important role in simulating distal femur fracture mechanics, and it is particularly critical that patient customized models attempt to accurately represent alignment of the bone fragments and lateral plate apposition., (© 2024 Orthopaedic Research Society.)

Mechanical deformation of polymer networks causes molecular-level motion and bond scission that ultimately lead to material failure. Mitigating this strain-induced loss in mechanical integrity is a significant challenge, especially in the development of active and shape-memory materials. We report the additive manufacturing of mechanical metamaterials made with a protein-based polymer that undergo a unique stiffening and strengthening behavior after shape recovery cycles. We utilize a bovine serum albumin-based polymer and show that cyclic tension and recovery experiments on the neat resin lead to a ~60% increase in the strength and stiffness of the material. This is attributed to the release of stored length in the protein mechanophores during plastic deformation that is preserved after the recovery cycle, thereby leading to a "strain learning" behavior. We perform compression experiments on three-dimensionally printed lattice metamaterials made from this protein-based polymer and find that, in certain lattices, the strain learning effect is not only preserved but amplified, causing up to a 2.5× increase in the stiffness of the recovered metamaterial. These protein-polymer strain learning metamaterials offer a unique platform for materials that can autonomously remodel after being deformed, mimicking the remodeling processes that occur in natural materials., Competing Interests: Competing interests statement:The authors declare no competing interest.

Microfluidics offer user-friendly liquid handling for a range of biochemical applications. 3D printing microfluidics is rapid and cost-effective compared to conventional cleanroom fabrication. Typically, microfluidics are 3D printed using digital light projection (DLP) stereolithography (SLA), but many models in use are expensive (≥$10,000 USD), limiting widespread use. Recent liquid crystal display (LCD) technology advancements have provided inexpensive (<$500 USD) SLA 3D printers with sufficient pixel resolution for microfluidic applications. However, there are only a few demonstrations of microfluidic fabrication, limited validation of print fidelity, and no direct comparisons between LCD and DLP printers. We compared a 40 μm pixel DLP printer (∼$18,000 USD) with a 34.4 μm pixel LCD printer (<$380 USD). Consistent with prior work, we observed linear trends between designed and measured channel widths ≥4 pixels on both printers, so we calculated accuracy above this size threshold. Using a standard IPA-wash resin and optimized parameters for each printer, the average error between designed and measured widths was 2.11 ± 1.26% with the DLP printer and 15.4 ± 2.57% with the 34.4 μm LCD printer. Printing with optimized conditions for a low-cost water-wash resin designed for LCD-SLA printers resulted in an average error of 2.53 ± 0.94% with the 34.4 μm LCD printer and 5.35 ± 4.49% with a 22 μm LCD printer. We characterized additional parameters including surface roughness, channel perpendicularity, and light intensity uniformity, and as an application of LCD-printed devices, we demonstrated consistent flow rates in capillaric circuits for self-regulated and self-powered delivery of multiple liquids. LCD printers are an inexpensive alternative for fabricating microfluidics, with minimal differences in fidelity and accuracy compared with a 40X more expensive DLP printer., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

The quest for scarless wound healing is imperative in healthcare, aiming to diminish the challenges of conventional wound treatment. Hyaluronic acid (HA), a key component of the skin's extracellular matrix, plays a pivotal role in wound healing and skin rejuvenation. Leveraging the advantages of HA hydrogels, this research focuses first on tuning the physicochemical and mechanical properties of photo-crosslinkable methacrylated HA (MAHA) by varying the methacrylation degree, polymer concentration, photo-crosslinker concentration, and UV exposure time. The optimized hydrogel, featuring suitable porosity, swelling ratio, degradability, and mechanical properties, was then used for the combined delivery of tannic acid (TA), known for its hemostatic, antibacterial, and antioxidant properties, and Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) cultured on the MAHA-TA hydrogel to enhance skin regeneration. The composite MAHA-TA-MSC hydrogel demonstrated favorable pores and biocompatibility, evidenced by cell viability, and promoted cell proliferation. When applied to dorsal wounds in rats, this composite hydrogel accelerated wound healing and reduced scarring. Additionally, molecular and histopathological analyses revealed increased expression of IL-10, the TGF-β3/TGF-β1 ratio, and the Collagen III/Collagen I ratio. These findings suggest that the MAHA-TA-MSC hydrogel is a promising candidate for scarless acute wound healing., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)