Scholarly Works, Biomedical Engineering and Mechanics

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Red blood cell aggregation within a blood clot causes platelet-independent clot shrinkage
Peshkova, Alina; Rednikova, Ekaterina; Khismatullin, Rafael; Kim, Oleg; Muzykantov, Vladimir; Purohit, Prashant; Litvinov, Rustem; Weisel, John (American Society of Hematology, 2025-04-16)
Platelet-driven blood clot contraction (retraction) is important for hemostasis and thrombosis. RBCs occupy about half of the clot volume, but their possible active contribution to contraction is unknown. The work was aimed at elucidating the ability of RBCs to promote clot shrinkage. To distinguish effects of platelets and RBCs, we formed thrombin-induced clots from reconstituted human samples containing platelet-free plasma and platelet-depleted RBCs, followed by tracking the clot size. The clots before and after RBC-induced shrinkage were analyzed using histology and scanning electron microscopy. Tension developed in the RBC-containing plasma clots was measured with rheometry and theoretical modeling was used to elucidate the clot shrinkage mechanisms. Platelet-depleted clots formed in the presence of RBCs exhibited >20% volume shrinkage within one hour. This process was insensitive to blebbistatin, latrunculin A, and abciximab. At a higher RBC count clot shrinkage increased, whereas in the absence of RBCs no plasma clot shrinkage was observed. At low platelet counts RBCs stimulated clot contraction proportionately to the platelet level. Inside the shrunken clots, RBCs formed aggregates. The average tensile force per one RBC was ~120±100 pN. Clots from purified fibrinogen formed in the presence of RBCs did not change in size, but underwent shrinkage in the presence of osmotically active dextran. Blood clot shrinkage can be caused by RBCs alone and this effect is due to the RBC aggregation driven mainly by osmotic depletion. The RBC-induced clot shrinkage may reinforce platelet-driven blood clot contraction and promote clot compaction when there are few and/or dysfunctional platelets.
Transient Lymphatic Remodeling Follows Sub‑Ablative High‑Frequency Irreversible Electroporation Therapy in a 4T1 Murine Model
Esparza, Savieay; Jacobs, Edward; Hammel, Jennifer H.; Michelhaugh, Sharon K.; Alinezhadbalalami, Nastaran; Nagai‑Singer, Margaret; Imran, Khan Mohammad; Davalos, Rafael V.; Allen, Irving C.; Verbridge, Scott S.; Munson, Jennifer M. (Springer, 2025-02-25)
High-frequency irreversible electroporation (H-FIRE) is a minimally invasive local ablation therapy known to activate the adaptive immune system and reprogram the tumor microenvironment. Its predecessor, irreversible electroporation (IRE), transiently increases microvascular density and immune cell infiltration within the surviving non-ablated and non-necrotic tumor region, also known as the viable tumor region. However, the impact of pulse electric field therapies on lymphatic vessels, crucial for T-cell fate and maturation, remains unclear. This study investigates how sub-ablative H-FIRE (SA-HFIRE) affects lymphatic and blood microvascular remodeling in the 4T1 mammary mouse model. We conducted a temporal and spatial analysis to evaluate vascular changes in the viable tumor, peritumoral fat pad, and tumor-draining lymph node posttreatment. Histological examination showed a transient increase in blood vessel density on Day 1 post-treatment, followed by a spike in lymphatic vessel density in the viable tumor region on Day 3 post-treatment, increased lymphatic vessel density in the peripheral fat pad, and minimal remodeling of the tumor-draining lymph node within 3 days following treatment. Gene expression analysis indicated elevated levels of CCL21 and CXCL2 on Day 1 post-treatment, while VEGFA and VEGFC did not appear to contribute to vascular remodeling. Likewise, CCL21 protein content in tumor-draining axillary lymph nodes correlated with gene expression data from the viable tumor region. These findings suggest a dynamic shift in lymphatic and blood microvascular structures post-SA-HFIRE, potentially enhancing the adaptive immune response through CCL21- mediated lymphatic homing and subsequent lymph node microvascular remodeling. Future work will assess the immune and transport function of the microvasculature to inform experiments aimed at the application of adjuvant therapies during scenarios of tumor partial ablation.
Improvement in trunk kinematics after treadmill-based reactive balance training among older adults is strongly associated with trunk kinematics before training
Aviles, Jessica; Wright, David L.; Allin, Leigh J.; Alexander, Neil B.; Madigan, Michael L. (Elsevier, 2020-11-09)
Reactive balance training (RBT) is an emerging fall prevention exercise intervention for older adults. To better understand factors that influence improvements after RBT, the goal of this study was to identify key factors that strongly associate with training-induced improvements in reactive balance. This study is a secondary analysis of data from a prior study. Twenty-eight residents of senior housing facilities participated, including 14 RBT participants and 14 Tai Chi participants (controls). Before and one week after training, participants completed balance and mobility tests and a reactive balance test. Reactive balance was operationalized as the maximum trunk angle in response to standardized trip-like perturbations on a treadmill. Bivariate (Pearson) correlation was used to identify participant characteristics before RBT and measures of performance during RBT that associated with training-induced changes in maximum trunk angle. Maximum trunk angle before reactive balance training exhibited the strongest association with training-induced changes in maximum trunk angle among RBT participants (r2 = 0.84; p < .001), but not among Tai Chi participants (r2 = 0.17; p = .138). Measures of performance during RBT, based upon perturbation speed, also associated with RBT-induced improvements in maximum trunk angle. These results help clarify the characteristics of individuals who can benefit from RBT, and support the use of treadmill perturbation speed as a surrogate measure of training-induced improvements in trunk kinematics.
Potential Implementation of Reactive Balance Training within Continuing Care Retirement Communities
Aviles, Jessica; Porter, Gwenndolyn C.; Estabrooks, Paul A.; Alexander, Neil B.; Madigan, Michael L. (Lippincott Williams & Wilkins, 2020-03-15)
Purpose: The purpose of the study was to evaluate the feasibility of implementing reactive balance training (RBT) in continuing care retirement communities, as a part of typical practice in these facilities. Methods: RBT, a task-specific exercise program, consisted of repeatedly exposing participants to trip-like perturbations on a modified treadmill to improve reactive balance, and subsequently reduce fall risk. Semi-structured interviews were conducted with retirement community residents (RBT participants) and administrators, to assess the organizational context, perceptions of evidence for falls prevention, and facilitation strategies that could improve the likelihood of implementing RBT as a falls-prevention program. Results: Contextual factors such as leadership support, culture of change, evaluation capabilities, and receptivity to RBT among administrators and health leaders at the participating retirement communities could facilitate future implementation. The cost associated with RBT (e.g. equipment and personnel), resident recruitment, and accessibility of RBT for many residents were identified as primary barriers related to the intervention. Participants perceived observable health benefits after completing RBT, had increased awareness toward tripping, and greater confidence with respect to mobility. Across interviewees potential barriers for implementation regarding facilitation revolved around the compatibility and customizability for different participant capabilities that would need to be considered before adopting RBT. Conclusion: RBT could fill a need in retirement communities and the findings provide areas of context, characteristics of the intervention, and facilitation approaches that could improve uptake.
Comparison of Treadmill Trip-Like Training Versus Tai Chi to Improve Reactive Balance Among Independent Older Adult Residents of Senior Housing: A Pilot Controlled Trial
Aviles, Jessica; Allin, Leigh J.; Alexander, Neil B.; Van Mullekom, Jennifer; Nussbaum, Maury A.; Madigan, Michael L. (Oxford University Press, 2018-12-21)
Background: There is growing interest in using perturbation-based balance training to improve the reactive response to common perturbations (eg, tripping and slipping). The goal of this study was to compare the efficacy of treadmill-based reactive balance training versus Tai Chi performed at, and among independent residents of, older adult senior housing. Methods: Thirty-five residents from five senior housing facilities were allocated to either treadmill-based reactive balance training or Tai Chi training. Both interventions were performed three times per week for 4 weeks, with each session lasting approximately 30 minutes. A battery of balance tests was performed at baseline, and again 1 week, 1 month, 3 months, and 6 months post-training. The battery included six standard clinical tests of balance and mobility, and a test of reactive balance performance. Results: At baseline, no significant between-group differences were found for any balance tests. After training, reactive balance training participants had better reactive balance than Tai Chi participants. Maximum trunk angle was 13.5 smaller among reactive balance training participants 1 week after training (p =. 01), and a reactive balance rating was 24%-31% higher among reactive balance training participants 1 week to 6 months after training (p <. 03). Clinical tests showed minimal differences between groups at any time point after training. Conclusion: Trip-like reactive balance training performed at senior housing facilities resulted in better rapid balance responses compared with Tai Chi training.
A Reactive Balance Rating Method That Correlates With Kinematics After Trip-like Perturbations on a Treadmill and Fall Risk Among Residents of Older Adult Congregate Housing
Madigan, Michael L.; Aviles, Jessica; Allin, Leigh J.; Nussbaum, Maury A.; Alexander, Neil B. (Oxford University Press, 2018-04-16)
Background: A growing number of studies are using modified treadmills to train reactive balance after trip-like perturbations that require multiple steps to recover balance. The goal of this study was thus to develop and validate a low-tech reactive balance rating method in the context of trip-like treadmill perturbations to facilitate the implementation of this training outside the research setting. Methods: Thirty-five residents of five senior congregate housing facilities participated in the study. Participants completed a series of reactive balance tests on a modified treadmill from which the reactive balance rating was determined, along with a battery of standard clinical balance and mobility tests that predict fall risk. We investigated the strength of correlation between the reactive balance rating and reactive balance kinematics. We compared the strength of correlation between the reactive balance rating and clinical tests predictive of fall risk with the strength of correlation between reactive balance kinematics and the same clinical tests. We also compared the reactive balance rating between participants predicted to be at a high or low risk of falling. Results: The reactive balance rating was correlated with reactive balance kinematics (Spearman's rho squared = .04-.30), exhibited stronger correlations with clinical tests than most kinematic measures (Spearman's rho squared = .00-.23), and was 42%-60% lower among participants predicted to be at a high risk for falling. Conclusion: The reactive balance rating method may provide a low-tech, valid measure of reactive balance kinematics, and an indicator of fall risk, after trip-like postural perturbations.
Relative Strength at the Hip, Knee, and Ankle Is Lower Among Younger and Older Females Who Are Obese
Koushyar, Hoda; Nussbaum, Maury A.; Davy, Kevin P.; Madigan, Michael L. (Lippincott Williams & Wilkins, 2016-03-22)
Background and Purpose: The mobility of individuals who are obese can be limited compared with their healthy weight counterparts. Lower limb strength has been associated with mobility, and reduced strength may contribute to mobility limitation among individuals who are obese. However, our understanding of the effects of obesity on lower limb strength is limited. The purpose of this study was to investigate the effects of obesity and age on extension and flexion strength at the hip, knee, and ankle. Methods: Using a cross-sectional design, 10 younger (18-30 years) healthy weight (body mass index = 18-24.9 kg/m2), 10 younger obese (body mass index >30 kg/m2), 10 older (65-80 years) healthy weight, and 10 older obese female participants performed isokinetic maximum voluntary contractions in ankle plantar flexion (PF), ankle dorsiflexion (DF), knee extension (KE), knee flexion (KF), hip extension (HE), and hip flexion (HF). Results and Discussion: Absolute strength among obese participants was 29% higher in DF (P =.002), 27% higher in KE (P =.004), and 23% higher in HF (P =.001), compared with healthy weight participants. Strength relative to body mass among obese participants was 31% lower in PF (P <.001), 14% lower in DF (P =.042), 16% lower in KE (P =.015), 27% lower in KF (P <.001), 29% lower in HE (P <.001), and 19% lower in HF (P =.001). Conclusions: Obese females exhibited lower relative strength at the ankle and hip, similar to the lower relative strength exhibited at the knee. Obese females also exhibited higher absolute strength, but only for 3 of 6 lower limb exertions investigated. This lack of uniformity across the 6 exertions is likely due to the still unclear underlying biomechanical mechanism responsible for these strength differences, which may also be influenced by aging. The effects of obesity on lower limb strength were also generally consistent between the 2 age groups investigated.
Effects of a low-cost prosthetic knee on amputee gait over uneven and even terrains
Aviles, Jessica; Castleberry, Julia; Madigan, Michael L. (Wolters Kluwer Health, 2024-11-05)
Limited data are available related to using a low-cost prosthetic knee while walking. To address this gap, this study compared the performance of a low-cost prosthetic knee with 2 more advanced prosthetic knees while walking on even and uneven terrains. Two adult subjects with above-knee amputations completed walking trials using a low-cost prosthetic knee (ReMotion knee) and their personal prosthetic knees (Ottobock 3R60 Pro mechanical knee and Ossur Rheo microprocessor knee) over even and uneven terrains. Several measures of gait performance were obtained including step size, stability, energy expenditure, as well as user perception of ReMotion workload and performance during gait. Effects of the ReMotion knee were different between the mechanical and microprocessor knee user. In addition, subjects perceived the positive aspects associated with the ReMotion knee to be its lightweight feature and their perceived increased in stability during walking while both subjects disliked the inability of the ReMotion knee to adjust to preferred walking speeds. This study provided an understanding of low-cost prosthetic technology among lower-limb amputees compared to prosthetic technology with more technologically advanced assistance. These findings may help guide future low-cost prosthetic knee design considerations for use on various terrains.
Approximate Bayesian Techniques for Statistical Model Selection and Quantifying Model Uncertainty-Application to a Gait Study
Franck, Christopher T.; Arena, Sara L.; Madigan, Michael L. (Springer, 2022-08-20)
Frequently, biomedical researchers need to choose between multiple candidate statistical models. Several techniques exist to facilitate statistical model selection including adjusted R2, hypothesis testing and p-values, and information criteria among others. One particularly useful approach that has been slow to permeate the biomedical literature is the notion of posterior model probabilities. A major advantage of posterior model probabilities is that they quantify uncertainty in model selection by providing a direct, probabilistic comparison among competing models as to which is the “true” model that generated the observed data. Additionally, posterior model probabilities can be used to compute posterior inclusion probabilities which quantify the probability that individual predictors in a model are associated with the outcome in the context of all models considered given the observed data. Posterior model probabilities are typically derived from Bayesian statistical approaches which require specialized training to implement, but in this paper we describe an easy-to-compute version of posterior model probabilities and inclusion probabilities that rely on the readily-available Bayesian information criterion. We illustrate the utility of posterior model probabilities and inclusion probabilities by re-analyzing data from a published gait study investigating factors that predict required coefficient of friction between the shoe sole and floor while walking.
Head kinematics of human subjects during laboratory-induced ladder falls to the ground
Ferro, Gabrielle M.; Rowson, Steven; Madigan, Michael L. (Pergamon-Elsevier, 2024-08-20)
Introduction: Fall-induced traumatic brain injury (TBI) is considered one of the most serious occupational injuries in construction. Given the frequency of falls from ladders, knowledge of head kinematics during ladder falls to the ground may help inform any potential improvement to construction safety helmet design and improve their protection against head injury. Therefore, the goal of this descriptive study was to measure head kinematics during laboratory-induced ladder falls to the ground. Method: Eighteen young adults wearing a hockey helmet simulated construction tasks that challenged their balance while standing on stepladders and an extension ladder with their feet at heights up to 1.8 m above padding covering the ground. Falls onto the padding occurred spontaneously or were induced by an investigator nudging the ladder to simulate ladder movement resulting from the ground shifting. Optoelectronic motion capture was used to capture head kinematics up to the instant immediately before head impact. Results: Of 115 total falls, 15 involved head impact with the padding and were analyzed. Head impact during all 15 of these falls occurred on the back of the head. Immediately before impact with the padding, head vertical velocity ranged from 0.42 to 3.88 m/s and head angular velocity about a medial–lateral axis ranged from 60.1 to 1215.5 deg/s. Conclusions: These data can be used with computer simulations or headform impact testing to estimate true head impact kinematics, or to inform future versions of construction safety helmet testing standards. Practical applications: This is the first study we are aware of to capture head kinematics of human subjects during ladder falls to the ground. These results have the potential to inform future versions of construction safety helmet testing standards and contribute to improved helmet design for protection against fall-induced head injury.
Effect of processing parameters and thermal history on microstructure evolution and functional properties in laser powder bed fusion of 316L
Deshmukh, Kaustubh; Riensche, Alex; Bevans, Ben; Lane, Ryan J.; Snyder, Kyle; Halliday, Harold (Scott); Williams, Christopher B.; Mirzaeifar, Reza; Rao, Prahalada (Elsevier, 2024-07-03)
In this paper, we explain and quantify the causal effect of processing parameters and part-scale thermal history on the evolution of microstructure and mechanical properties in the laser powder bed fusion additive manufacturing of Stainless Steel 316L components. While previous works have correlated the processing parameters to flaw formation, microstructures evolved, and properties, a missing link is the understanding of the effect of thermal history. Accordingly, tensile test coupons were manufactured under varying processing conditions, and their microstructure-related attributes, e.g., grain morphology, size and texture; porosity; and microhardness were characterized. Additionally, the yield and tensile strengths of the samples were measured using digital image correlation. An experimentally validated computational model was used to predict the thermal history of each sample. The temperature gradients and sub-surface cooling rates ascertained from the model predictions were correlated with the experimentally characterized microstructure and mechanical properties. By elucidating the fundamental process-thermal-structure–property relationship, this work establishes the foundation for future physics-based prediction of microstructure and functional properties in laser powder bed fusion.
Reverse social contagion as a mechanism for regulating mass behaviors in highly integrated social systems
Porfiri, Maurizio; De Lellis, Pietro; Aung, Eighdi; Meneses, Santiago; Abaid, Nicole; Waters, Jane S.; Garnier, Simon (Oxford University Press, 2024-06-26)
Mass behavior is the rapid adoption of similar conduct by all group members, with potentially catastrophic outcomes such as mass panic. Yet, these negative consequences are rare in integrated social systems such as social insect colonies, thanks to mechanisms of social regulation. Here, we test the hypothesis that behavioral deactivation between active individuals is a powerful social regulator that reduces energetic spending in groups. Borrowing from scaling theories for human settlements and using behavioral data on harvester ants, we derive ties between the hypermetric scaling of the interaction network and the hypometric scaling of activity levels, both relative to the colony size. We use elements of economics theory and metabolic measurements collected with the behavioral data to link activity and metabolic scalings with group size. Our results support the idea that metabolic scaling across social systems is the product of different balances between their social regulation mechanisms.
Learning from Experience: A Faculty-Led Collaborative Inquiry Exploring Embedded Communication Skills Across Engineering Curricula
Biviano, Angelo; Branscome, Caroline; Burgoyne, Christine Bala; Carper, Kathleen; Iorio, Josh; Scarff, Kelly; Taylor, Ashley R.; Arena, Sara (ASEE Conferences, 2024-06-23)
This evidence-based practice paper describes a collaborative inquiry process to explore a critical question for engineering faculty: what are practical strategies for leveraging evidence-based practices to embed communication skills across core engineering curricula? Within engineering education, there is a growing consensus that communication skills are essential for engineering graduates. For example, the Accreditation Board for Engineering and Technology (ABET) distinctly highlights communication skills as a required student learning outcome for accreditation of engineering programs in ABET Criterion 3.3.: an ability to communicate effectively with a range of audiences. Numerous studies exploring engineers’ school-to-work transition suggest that communication is one of the most important skill sets for engineering practice according to both recent graduates (Passow, 2012) and industry (Male et. al, 2010). As the Engineer of 2020 Report concisely noted, “good engineering will require good communication” (National Academy of Engineering, 2004, p. 56). Despite the engineering education community’s shared vision for ensuring engineering graduates can communicate effectively, few practical examples exist to illuminate how faculty can leverage evidence-based practices to integrate communication skills into their existing technical curricula. Therefore, the purpose of this paper is to share seven practical case-based examples of strategies implemented in a spectrum of engineering disciplines and learning environments to support faculty in integrating communication skills into existing engineering curriculum. We first describe our collaborative inquiry process to create a “systematic structure for learning from experience” (Yorks & Kasl, 2002, p. 3). Our learning from experience is rooted in the reflections of faculty representing seven engineering departments who teach communication skills across a diverse range of engineering curricular contexts (e.g., course size, course level, technical subject, etc.) Next, we provide seven case studies of evidence-based strategies-in-action across this range of learning contexts, including both undergraduate and graduate education. For example, one case study discusses the integration of a community-focused debate project in a mining engineering undergraduate course to build students’ communications skills in rhetorical situation analysis while another study in a construction engineering management department attends to aspects of diversity and inclusion by promoting a writing process that begins with visual design. These case studies provide rich context for the learning environment and the implementation of the evidence-based practice, with the ultimate goal of supporting faculty in drawing connections to their own teaching strategies. Finally, we conclude by situating the case studies in the broader engineering education literature and sharing reflections for lessons learned on integration of communication instruction across existing engineering curricula.
First-In-DOg HISTotripsy for Intracranial Tumors Trial: The FIDOHIST Study
Vezza, Christina; Ruger, Lauren; Langman, Maya; Vickers, Elliana; Prada, Francesco; Sukovich, Jonathan; Hall, Timothy; Xu, Zhen; Parker, Rell L.; Vlaisavljevich, Eli; Rossmeisl, John H. (SAGE Publications, 2024-10-17)
Objective: Brain tumors represent some of the most treatment refractory cancers, and there is a clinical need for additional treatments for these tumors. Domesticated dogs are the only other mammalian species which commonly develop spontaneous brain tumors, making them an ideal model for investigating novel therapies. Histotripsy is a non-thermal ultrasonic ablation method that emulsifies tissue through acoustic cavitation. The primary objectives of this prospective study were to assess the feasibility and safety of histotripsy to ablate naturally occurring canine brain tumors. Secondary endpoints included characterization of magnetic resonance imaging (MRI) responses to histotripsy treatment, and exploratory immunogenomic tumor response analyses. Methods: The study design utilized a treat and resect paradigm, where tumors were approached using craniotomy, partially ablated with histotripsy delivered through the cranial defect, imaged with MRI, and then resected. Dogs were evaluated with clinical, brain MRI, immunopathologic, and genomic examinations before treatment, intraoperatively, and 1, 14, and 42 days post-treatment. Here we report the results of the three dogs with meningiomas, all of which were treated with a custom eight element 1 MHz histotripsy transducer at a pulse repetition frequency of 100 Hz and a treatment dosage of 400 pulses/point. Results: Histotripsy was successfully delivered to all dogs, resulting in histopathologic evidence of ablations that were sharply demarcated from untreated tumor, with measured treatments approximating planned volumes in 2/3 dogs. One dog experienced an adverse event consisting of transient cerebral edema that was possibly attributable to histotripsy. Histotripsy ablations could be grossly visualized and identified on MRI, with features consistent with hemorrhage and necrosis. Significant expression or upregulation of the damage associated molecular pattern HMGB1, cytokine-cytokine receptor interaction, and NF-κb signaling pathways were observed in histotripsy treated tumors. Conclusion: Ablation of canine meningiomas with histotripsy through an open cranial window was feasible and clinically well tolerated.
Durotaxis and extracellular matrix degradation promote clustering of cancer cells
Potomkin, Mykhailo; Kim, Oleg V.; Klymenko, Yuliya; Alber, Mark; Aronson, Igor S. (Elsevier, 2025-01-24)
Early stages of metastasis depend on the collective behavior of cancer cells and their interaction 23 with the extracellular matrix (ECM). Cancer cell clusters are known to exhibit higher metastatic 24 potential than single cells. To explore clustering dynamics, we developed a calibrated computa- 25 tional model describing how motile cancer cells biochemically and biomechanically interact with 26 the ECM during the initial invasion phase, including ECM degradation and mechanical remod- 27 eling. The model reveals that cluster formation time, size, and shape are influenced by ECM 28 degradation rates and cellular responsiveness to external stresses (durotaxis). The results align 29 with experimental observations, demonstrating distinct cell trajectories and cluster morphologies 30 shaped by biomechanical parameters. These simulations provide valuable insights into cancer 31 invasion dynamics and may suggest potential therapeutic strategies targeting early-stage inva- 32 sive cells.
Cancer detection in dogs using rapid Raman molecular urinalysis
Robertson, John L.; Dervisis, Nikolaos G.; Rossmeisl, John H. Jr.; Nightengale, Marlie; Fields, Daniel; Dedrick, Cameron; Ngo, Lacey; Issa, Amr Sayed; Guruli, Georgi; Orlando, Giuseppe; Senger, Ryan S. (Frontiers, 2024-02-07)
Introduction: The presence of cancer in dogs was detected by Raman spectroscopy of urine samples and chemometric analysis of spectroscopic data. The procedure created a multimolecular spectral fingerprint with hundreds of features related directly to the chemical composition of the urine specimen. These were then used to detect the broad presence of cancer in dog urine as well as the specific presence of lymphoma, urothelial carcinoma, osteosarcoma, and mast cell tumor. Methods: Urine samples were collected via voiding, cystocentesis, or catheterization from 89 dogs with no history or evidence of neoplastic disease, 100 dogs diagnosed with cancer, and 16 dogs diagnosed with non-neoplastic urinary tract or renal disease. Raman spectra were obtained of the unprocessed bulk liquid urine samples and were analyzed by ISREA, principal component analysis (PCA), and discriminant analysis of principal components (DAPC) were applied using the Rametrix®Toolbox software. Results and discussion: The procedure identified a spectral fingerprint for cancer in canine urine, resulting in a urine screening test with 92.7% overall accuracy for a cancer vs. cancer-free designation. The urine screen performed with 94.0% sensitivity, 90.5% specificity, 94.5% positive predictive value (PPV), 89.6% negative predictive value (NPV), 9.9 positive likelihood ratio (LR+), and 0.067 negative likelihood ratio (LR-). Raman bands responsible for discerning cancer were extracted from the analysis and biomolecular associations were obtained. The urine screen was more effective in distinguishing urothelial carcinoma from the other cancers mentioned above. Detection and classification of cancer in dogs using a simple, non-invasive, rapid urine screen (as compared to liquid biopsies using peripheral blood samples) is a critical advancement in case management and treatment, especially in breeds predisposed to specific types of cancer.
Reinforcement learning processes as forecasters of depression remission
Bansal, Vansh; McCurry, Katherine L.; Lisinski, Jonathan; Kim, Dong-Youl; Goyal, Shivani; Wang, John M.; Lee, Jacob; Brown, Vanessa M.; LaConte, Stephen M.; Casas, Brooks; Chiu, Pearl H. (Elsevier, 2024-09-11)
Background: Aspects of reinforcement learning have been associated with specific depression symptoms and may inform the course of depressive illness. Methods: We applied support vector machines to investigate whether blood‑oxygen-level dependent (BOLD) responses linked with neural prediction error (nPE) and neural expected value (nEV) from a probabilistic learning task could forecast depression remission. We investigated whether predictions were moderated by treatment use or symptoms. Participants included 55 individuals (n = 39 female) with a depression diagnosis at baseline; 36 of these individuals completed standard cognitive behavioral therapy and 19 were followed during naturalistic course of illness. All participants were assessed for depression diagnosis at a follow-up visit. Results: Both nPE and nEV classifiers forecasted remission significantly better than null classifiers. The nEV classifier performed significantly better than the nPE classifier. We found no main or interaction effects of treatment status on nPE or nEV accuracy. We found a significant interaction between nPE-forecasted remission status and anhedonia, but not for negative affect or anxious arousal, when controlling for nEV-forecasted remission status. Limitations: Our sample size, while comparable to that of other studies, limits options for maximizing and evaluating model performance. We addressed this with two standard methods for optimizing model performance (90:10 train and test scheme and bootstrapped sampling). Conclusions: Results support nEV and nPE as relevant biobehavioral signals for understanding depression outcome independent of treatment status, with nEV being stronger than nPE as a predictor of remission. Reinforcement learning variables may be useful components of an individualized medicine framework for depression healthcare.
Stabilizing milk-derived extracellular vesicles (mEVs) through lyophilization: a novel trehalose and tryptophan formulation for maintaining structure and Bioactivity during long-term storage
Dogan, Alan B.; Marsh, Spencer R.; Tschetter, Rachel J.; Beard, Claire E.; Amin, Md R.; Jourdan, L. Jane; Gourdie, Robert G. (2025-01-13)
Extracellular vesicles (EVs) are widely investigated for their implications in cell-cell signaling, immune modulation, disease pathogenesis, cancer, regenerative medicine, and as a potential drug delivery vector. However, maintaining integrity and bioactivity of EVs between Good Manufacturing Practice separation/filtration and end-user application remains a consistent bottleneck towards commercialization. Milk-derived extracellular vesicles (mEVs), separated from bovine milk, could provide a relatively low-cost, scalable platform for large-scale mEV production; however, the reliance on cold supply chain for storage remains a logistical and financial burden for biologics that are unstable at room temperature. Herein, we aim to characterize and engineer a freeze-dried, mEV formulation that can be stored at room temperature without sacrificing structure/bioactivity and can be reconstituted before delivery. In addition to undertaking established mEV assays of structure and function on our preparations, we introduce a novel, efficient, high throughput assay of mEV bioactivity based on Electric Cell Substrate Impedance Sensing (ECIS) in Human dermal fibroblast monolayers. By adding appropriate excipients, such as trehalose and tryptophan, we describe a protective formulation that preserves mEV bioactivity during long-term, room temperature storage. Our identification of the efficacy of tryptophan as a novel additive to mEV lyophilization solutions could represent a significant advancement in stabilizing small extracellular vesicles outside of cold storage conditions.
Gradient descent optimization of acoustic holograms for transcranial focused ultrasound
Sallam, Ahmed; Cengiz, Ceren; Pewekar, Mihir; Hoffmann, Eric; Legon, Wynn; Vlaisavljevich, Eli; Shahab, Shima (AIP Publishing, 2024-10-08)
Acoustic holographic lenses, also known as acoustic holograms, can change the phase of a transmitted wavefront in order to shape and construct complex ultrasound pressure fields, often for focusing the acoustic energy on a target region. These lenses have been proposed for transcranial focused ultrasound (tFUS) to create diffraction-limited focal zones that target specific brain regions while compensating for skull aberration. Holograms are currently designed using time-reversal approaches in full-wave time-domain numerical simulations. Such simulations need time-consuming computations, which severely limits the adoption of iterative optimization strategies. In the time-reversal method, the number and distribution of virtual sources can significantly influence the final sound field. Because of the computational constraints, predicting these effects and determining the optimal arrangement is challenging. This study introduces an efficient method for designing acoustic holograms using a volumetric holographic technique to generate focused fields inside the skull. The proposed method combines a modified mixed-domain method for ultrasonic propagation with a gradient descent iterative optimization algorithm. The findings are further validated in underwater experiments with a realistic 3D-printed skull phantom. This approach enables substantially faster holographic computation than previously reported techniques. The iterative process uses explicitly defined loss functions to bias the ultrasound field’s optimization parameters to specific desired characteristics, such as axial resolution, transversal resolution, coverage, and focal region uniformity, while eliminating the uncertainty associated with virtual sources in time-reversal techniques. The proposed techniques enable more rapid hologram computation and more flexibility in tailoring ultrasound fields for specific therapeutic requirements.
Quantitative ultrasound assessment of fatty infiltration of the rotator cuff muscles using backscatter coefficient
Toto-Brocchi, Marco; Wu, Yuanshan; Jerban, Saeed; Han, Aiguo; Andre, Michael; Shah, Sameer B.; Chang, Eric Y. (2024-10-22)
Background: To prospectively evaluate ultrasound backscatter coefficients (BSCs) of the supraspinatus and infraspinatus muscles and compare with Goutallier classification on magnetic resonance imaging (MRI). Methods: Fifty-six participants had shoulder MRI exams and ultrasound exams of the supraspinatus and infraspinatus muscles. Goutallier MRI grades were determined and BSCs were measured. Group means were compared and the strength of relationships between the measures were determined. Using binarized Goutallier groups (0–2 versus 3–4), areas under the receiver operating characteristic curves (AUROCs) were calculated. The nearest integer cutoff value was determined using Youden’s index. Results: BSC values were significantly different among most Goutallier grades for the supraspinatus and infraspinatus muscles (both p < 0.001). Strong correlations were found between the BSC values and Goutallier grades for the supraspinatus (τb = 0.72, p < 0.001) and infraspinatus (τb = 0.79, p < 0.001) muscles. BSC showed excellent performance for classification of the binarized groups (0–2 versus 3–4) for both supraspinatus (AUROC = 0.98, p < 0.0001) and infraspinatus (AUROC = 0.98, p < 0.0001) muscles. Using a cutoff BSC value of −17 dB, sensitivity, specificity, and accuracy for severe fatty infiltration were 87.0%, 90.0%, and 87.5% for the supraspinatus muscle, and 93.6%, 87.5%, and 92.7% for the infraspinatus muscle. Conclusion: BSC can be applied to the rotator cuff muscles for assessment of fatty infiltration. For both the supraspinatus and infraspinatus muscles, BSC values significantly increased with higher Goutallier grades and showed strong performance in distinguishing low versus high Goutallier grades. Relevance statement: Fatty infiltration of the rotator cuff muscles can be quantified using BSC values, which are higher with increasing Goutallier grades. Key Points Ultrasound BSC measurements are reliable for the quantification of muscle fatty infiltration. BCS values increased with higher Goutallier MRI grades. BCS values demonstrated high performance for distinguishing muscle fatty infiltration groups.

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