Computer Methods in Biomechanics and Biomedical Engineering
○ Informa UK Limited
Preprints posted in the last 30 days, ranked by how well they match Computer Methods in Biomechanics and Biomedical Engineering's content profile, based on 10 papers previously published here. The average preprint has a 0.01% match score for this journal, so anything above that is already an above-average fit.
Khassetarash, A.; Edwards, W. B.
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The relationship between external forces and bone strain in running is often complex and nonintuitive. We used Groucho running (i.e., running with exaggerated knee flexion) as a model to dramatically reduce the vertical ground reaction force (VGRF) and examined the relationship between peak VGRF and finite element (FE)-predicted tibia-fibula bone strain. Nine physically active males ran on an instrumented treadmill at 2.8 m/s with their preferred running technique, increased knee flexion (Groucho), and exaggerated knee flexion (Ex Groucho) in a randomized order. Strains at the tibia-fibula midshaft were calculated using computed-tomography-based FE modeling with loads and boundary conditions calculated from an inverse-dynamics based musculoskeletal model. Pressure-modified von Mises strain was used to quantify the peak strain (90th percentile strain) and strained volume (volume of bone experiencing strains above 3000 {micro}{varepsilon}). We further explored the relationship between peak VGRF, lower leg angle, and FE-predicted strain variables. The results showed that a 15.8% and 22.9% reduction in VGRF during Groucho and Ex Groucho, respectively, had no significant effect on FE-predicted peak strain (p > 0.304) and strained volume (p>0.053). Changes in peak VGRF did not correlate with FE-predicted strain variables (p>0.54) while changes in lower leg angle in the sagittal plane were moderately correlated (r>0.65; p<0.047). Our findings suggest that reductions in peak external forces do not always coincide with reductions in bone strain, especially in cases where running kinematics are dramatically altered. This work has important implications for designing gait retraining interventions based on reductions in external force measures.
Gao, L.; Gao, S.; Fekete, G.; Lu, Z.; Gao, Z.
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ObjectiveThis study investigates knee joint biomechanics during lunges under varying tibial angles and external loads using musculoskeletal modeling and finite element analysis. The goal is to provide a biomechanical basis for understanding knee loading patterns and optimizing sports training and rehabilitation. MethodsTwenty-six healthy young men performed lunges under tibial inclination angles relative to the ground (60{degrees} and 90{degrees}) and two external load conditions (bodyweight and an additional 98 N external load). Kinematic and kinetic data were captured using motion capture and force plates. Musculoskeletal models were used to estimate joint moments, range of motion, and stiffness, with data analyzed using two-way repeated-measures ANOVA. Finite element analysis was performed at 90{degrees} tibial angle to evaluate tissue stress and displacement. ResultsThe joint moment at a 60{degrees} tibial angle was much higher than at a 90{degrees}. External load showed significant effects on knee stiffness, with lower rotational stiffness in the horizontal plane (P < 0.001) and lower coronal plane stiffness at 90{degrees} (P = 0.012) under the 98 N external-load condition, indicating reduced resistance to angular displacement in these planes. Under the 90{degrees} tibial-angle condition with external load, peak stress and displacement were concentrated in the posterior horn of the meniscus, with a maximum displacement of 3.12 mm. ConclusionThe anterior tilt of the tibia increased sagittal-plane knee loading, while external load mainly reduced joint stiffness in the coronal and horizontal planes. Under the 90{degrees} loaded condition, the concentration of stress and displacement in the posterior horn of the meniscus suggests a mechanically unfavorable loading pattern rather than direct evidence of injury risk. These findings may provide useful biomechanical information for load management during lunge-based training and rehabilitation.
Liu, X.; Fang, W.; Perlin, K.
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Classical neuronal cable theory relies on quasi-static electric field approximations and neglects magnetic induction, Lorentz force coupling, and transient electromagnetic currents, limiting its ability to fully characterize action potential propagation within geometrically branched axons and dendrites. This work develops a coupled Maxwell-electromagnetic cable framework by integrating finite-difference time-domain (FDTD) solutions of Maxwells equations with extended Hodgkin-Huxley and Fitzhugh-Nagumo membrane dynamics, incorporating magnetic gating perturbations, electromagnetic trans-membrane currents IEM, and nanoscale quantum corrections for thin neural segments. Controlled propagation experiments are designed to quantify deviations from standard cable predictions across asymmetric and symmetric axonal bifurcation geometries. Numerical results demonstrate that inductive magnetic effects lower the critical branch radius for junction conduction failure and break symmetric action potential invasion in geometrically identical child branches under external transverse magnetic fields. An electromagnetic corrected geometric ratio GREM is proposed to revise impedance-matching conditions at branch points, accounting for size-dependent axial current imbalance induced by magnetic and displacement currents. Parent axon conduction velocity deviates substantially from the canonical [Formula] scaling law when electromagnetic feedback and quantum charge distributions are included, triggering early signal blockage at large cable diameters. Collectively, this study establishes that quasi-static cable models underestimate electromagnetic corrections to propagation speed, waveform shape, and bifurcation transmission fidelity; the coupled Maxwell-cable framework provides a comprehensive multi-physics tool for modeling electrodynamic signal behavior in complex neuronal architectures.
Stansfield, E.; Kainz, H.
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Most widely used lower-limb musculoskeletal models are derived from male anatomy and adapted to female participants solely by linear scaling, which may not capture sex-specific differences in pelvic and hip geometry. We developed a population-averaged, female lower-limb musculoskeletal model, built from MRI-based models of a cohort of 25 adult women using thin-plate-spline muscle-path mapping, bilateral symmetrisation, and wrapping-surface optimisation. We hypothesised that this average model, adapted to a new individual by standard linear scaling alone, would reproduce that individual's MRI-based model's walking biomechanics more closely than a linearly scaled generic male-based model. We also expected that this advantage would be concentrated in pelvis- and hip-dependent outputs rather than distributed evenly across all joints. Using 5-fold cross-validation, the scaled average-female model and the scaled male model were each compared against the held-out individual's MRI-based model across gait kinematics, joint moments, muscle moment arms, muscle forces/activations, and joint reaction forces. The average-female model outperformed the male model in every output category (Holm-corrected p [≤] *10-5), supporting our primary hypothesis. Consistent with our secondary hypothesis, differences were largest and most sustained for pelvis tilt, hip flexion, and gluteal/adductor moment arms and forces, and smaller for knee and ankle kinematics. Some divergence remained localised to early-stance knee kinematics and patellofemoral loading. The population-averaged female musculoskeletal model is freely available on SimTK https://simtk.org/projects/aver_fem and is recommended for studies involving female participants, particularly when pelvic and hip biomechanics are the primary outcomes.
Pryymachenko, Y.; Wilson, R.; Abbott, J. H.
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Background Little evidence is available on the epidemiology of different knee injuries at a whole-of-population level. The objective of this article is to provide accurate estimates of knee injury incidence by harnessing the unique comprehensive, population-wide data of New Zealand's universal no-fault injury insurance provider, the Accident Compensation Corporation (ACC). Methods We obtained insurance claims data from ACC covering all knee injury insurance claims approved between 2015 and 2024. We calculated the number of injuries and the incidence rate per 100 000 population, by injury type, year, sex, ethnicity, and age. Results The total number of injuries increased from 184 710 (4 067 per 100 000 population) in 2015 to 244 155 (4 701 per 100 000) in 2024. The most common injuries were other/unspecified ligament sprains, contusions, and collateral ligament sprains. Ligament and cartilage injuries were more common for males than for females, while contusions were more common for females. Ligament tears and dislocations were more common in younger people (15 to 35 years of age), while cartilage injuries were more common at older ages (40 to 65 years). Discussion and Conclusions The rate of knee injuries observed in this study was higher than previously reported in other settings, probably due to broader coverage of injuries treated in primary and community care settings. A broad range of injuries were common, including those that have received less attention in the epidemiological literature to date. More research is needed on the prevention, burden, and outcomes of different knee injuries, beyond a narrow focus on cruciate ligament injuries.
Jahani, F.; Cardenas, B.; Manning, E. P.; Szafron, J.
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Pulmonary hypertension (PH) is characterized by progressive structural and mechanical remodeling of the pulmonary vasculature, yet few computational frameworks directly link disease mechanisms to longitudinal progression and therapeutic response. In this study, we utilized a multiscale pulmonary arterial growth and remodeling (G&R) framework to capture evolving functional metrics from rat models of PH. This framework couples morphometric tree hemodynamics, constrained mixture theory-based wall mechanics, and maladaptive cellular remodeling. Disease progression was driven by three mechanistically interpretable parameters governing excess smooth muscle production, remodeling activation, and passive stiffening. These parameters were calibrated to longitudinal monocrotaline (MCT) measurements of pressure, wall thickness, and stiffness from prior work using a multiobjective optimization. To show the predictive value of this model, we simulated therapeutic intervention within the same disease-specific framework by using functional cell-level responses to therapy to inform changes in parameter values. Calibration to the study-specific MCT dataset reproduced the temporal increases in pressure, wall thickness, and stiffness, demonstrating that the model could capture multiple features of vascular remodeling simultaneously, with R2 values of 0.81, 0.83, and 0.95, respectively. Simulated treatment reduced pressure, wall thickness, and stiffness. Predicted pressure and wall-thickness responses agreed closely with the corresponding experimental treatment effects, whereas stiffness recovery was overpredicted, suggesting that additional mechanisms may contribute to persistent vascular stiffening after intervention. The framework also captured the overall progression of pulmonary pressure increases across both aggregated MCT and Sugen-hypoxia datasets, suggesting utility across studies and animal models. This work outlines a physics-based, multiscale framework that simulated quantities of direct clinical interest in a mechanistically interpretable platform for linking pulmonary vascular remodeling and treatment response. It supports comparisons across experimental phenotypes and interventions while identifying where constitutive refinements are needed to improve predictive capability across phenotypes.
Dolgitzer, D.; Parajon, E.; Robinson, D. N.; Iglesias, P. A.
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Tumor spheroid mechanics arise from both the mechanical properties of individual cells and the adhesive interactions that organize them into tissues. The relative contribution of these two factors to the bulk mechanical behavior, however, remains difficult to disentangle experimentally. Here, we develop a computational model of micropipette aspiration to compare the mechanical response of isolated cells and multicellular spheroids within a common computational framework. By independently varying single-cell stiffness and cell-cell adhesion, we quantify their effects on aspiration dynamics, effective elastic modulus, and viscoelastic relaxation. Our results show that increasing single-cell stiffness substantially alters the mechanics of isolated cells but has limited influence on the effective elastic modulus of multicellular spheroids. In contrast, changes in cell-cell adhesion produce pronounced effects on spheroid effective elastic modulus. Nevertheless, both parameters increase the retardation time governing the transition from the initial elastic response to long-time viscous deformation. These findings suggest that multicellular elasticity is governed primarily by intercellular mechanical coupling, whereas the dynamical response to applied stress depends jointly on cell-scale mechanics and cell-cell adhesion.
Keegan, L.; Shoaf, K.
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Infectious disease dynamics is a growing, interdisciplinary field that aims to advance the understanding of how infectious diseases spread and how to control them. Most trainees enter the field through established disciplines and assemble ad hoc training and experience in infectious disease dynamics. As such, expectations for doctoral training remain largely implicit and highly variable across institutions. Other fields have formalized training expectations though defined training competencies, which promote transparency and alignment across institutions without prescribing specific approaches to training or research. In this paper, we set out to define the core competencies that characterize doctoral-level expertise in infectious disease dynamics. We assembled a team of seven people at the University of Utah and drafted a competency set. We then validated the competency set with experts in the field using an e-Delphi process. We did not restrict participation by location, job title, or sector. We set an a priori threshold for consensus to 70% and sent out two rounds of surveys to experts, asking them to rank the competencies by order of importance. Our team initially generated a list of 13 proposed Cross-cutting, 24 Applied Modeling, 17 Data Science, and 16 Theory competencies. After completing two rounds of validation, we validated two tracks comprised of 7 Cross-cutting, 10 Applied Modeling, and 12 Theory competencies. This study represents the first structured effort to define doctoral-level competencies in infectious disease that can help guide curriculum development, comprehensive exam preparation, and trainee evaluation, while also supporting alignment between academic training and workforce needs.
Makarov, V. A.; Calvo Tapia, C.; Villacorta-Atienza, J. A.; Aparicio-Rodriguez, G.; Manubens, P.; Diez-Hermano, S.; Oleaga, G.
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Time compaction theory is a general framework explaining how a brain can efficiently deal with dynamic situations occurring in, e.g., sports games. It involves a geometric representation of the time dimension, which enables effective learning and strategic action planning. The theory has recently received experimental support in humans. However, its current computational model has an important limitation: it does not account for deliberate waiting and speed modulation, behaviors ubiquitous in natural environments. This work substantially extends the original model formulation by a dimensional lifting of an n-D workspace into (n + 1)-D mental space, where time remains geometrically embedded. The proposed biologically inspired computational model can generate adaptive behavior across increasingly complex situations, from navigation in everyday social environments to competitive sports. Furthermore, by actively conditioning the expected responses of other agents and stabilizing future predictions, we introduce the concept of uncertainty points in sequences of generalized cognitive maps to support the generation of adaptive strategies in interactive environments, where future prediction has a limited time horizon. Thus, we provide a mechanism for chaining short-term solutions into long-term strategies, which is illustrated by simulating the behavior of a player in a real football game. Author summaryHumans often anticipate future interactions in dynamic environments. Many behaviors, such as avoiding other pedestrians, letting someone pass through a narrow corridor, or reproducing the kind of dribbling maneuvers performed by elite football players, require deciding not only where to move but also when to move. Existing theories suggest that the brain simplifies such situations by representing future interactions as static spatial maps, making them easier to learn and recall. However, current computational models cannot naturally account for common behaviors such as waiting, slowing down, or modulating speed. Here we show that these behaviors readily emerge if the model space is extended by an additional virtual coordinate that encodes accumulated waiting rather than physical time. The proposed model simultaneously admits a wide variety of behaviors, including speed modulation, multigoal decisions, and compound actions, while preserving the principles of time compaction. We illustrate the model in everyday situations and by reproducing two real football plays, comparing the observed behaviors with model simulations. Our results suggest computational principles through which the human brain may efficiently represent, memorize, and exploit dynamic situations.
Jakubowski, K. L.; Ludvig, D.; Perreault, E. J.; Lee, S. S.
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Ankle stiffness is decreased during movement compared to posture; however, the etiology of this decrease remains unknown. Determining what gives rise to this decrease is critical for understanding how humans successfully interact with their physical world and how that ability is compromised by functional impairments. While the triceps surae and Achilles tendon primarily dictate ankle stiffness, the relative contributions across posture and movement remain unknown. Therefore, our study sought to quantify the relative contributions of the muscle and tendon to ankle stiffness and how those contributions differ between posture and movement. We used our technique, which combines B-mode ultrasound imaging with joint-level perturbations, to quantify ankle, muscle, and tendon stiffness simultaneously. Since ankle, muscle, and tendon stiffness all scale with torque, participants matched torque between posture and movement tasks. During posture, the Achilles tendon is the dominant contributor to ankle stiffness. However, during movement, the triceps surae and Achilles tendon contribute more equally to ankle stiffness, which can be attributed to a significant decrease in muscle stiffness during movement. Here, we provide the first empirical data on how state-dependent properties of the triceps surae and Achilles tendon contribute to ankle stiffness in conditions relevant to locomotion.
Pryymachenko, Y.; Wilson, R.; Abbott, J. H.
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Objectives To analyse the long-term effects of a cruciate ligament (CL) injury on health and socioeconomic outcomes. Methods We used a comprehensive national injury insurance database to identify CL injuries occurring in New Zealand between 2009 and 2022, and employed a doubly robust staggered difference-in-differences research design to identify the effects of these injuries on outcomes up to 10 years after injury. The outcomes of interest were healthcare use (hospitalisations, emergency department visits, medications, knee replacement surgery for osteoarthritis), associated healthcare costs, and labour market outcomes (employment rates, income, and government benefit payments). Results We identified 61 344 CL injuries for inclusion in the analysis. Over 10-year follow-up, a CL injury resulted in increased healthcare use (0.6 more hospitalizations [95%CI 0.4 to 0.7], 1.7 more days spent in hospital [95%CI 1.3 to 2.1], 0.4 more emergency department visits [95%CI 0.3 to 0.6], 2.5 more outpatient visits [95%CI 1.8 to 3.2], and 4.7 more medications dispensed [95%CI -1.8 to 11.2]) and public healthcare costs ($7 537; 95%CI 5 888 to 9 186), reduced income (-$6 060; 95%CI -11 644 to -475), and increased benefit payments ($1 152; 95%CI 542 to 1 761). Conclusion CL injuries have long-term impacts on healthcare use and socioeconomic outcomes. Strategies to reduce the incidence of CL injuries have the potential to realise large health and economic benefits.
Holvoet, J.; Lejeune, P.; Perin, J.; Vandendaele, B.; Ligot, G.
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Accurate tree volume estimation is central to forest management and carbon accounting. Allometric equations are widely used but limited in transferability across species, regions, and environmental conditions. Mobile Laser Scanning (MLS) offers a promising alternative through direct measurement of tree geometry; however, the influence of tree shape on MLS accuracy remains poorly understood. This study evaluated MLS-derived estimates of stem diameters, total tree height, and merchantable stem volume against destructive reference measurements from 176 trees spanning eight species (four hardwood, four softwood) in Wallonia, Belgium. A Zeb Horizon RT scanner was used; tree architectural descriptors extracted from the point cloud were tested for associations with measurement error. Across 7,824 stem diameter measurements, MLS achieved a mean error of 0.46 cm, with precision declining above 15 m. MLS-derived height outperformed Vertex IV clinometer measurements for hardwood species (RMSE% = 6.88 vs. 8.78) but performed slightly less well for softwoods (RMSE% = 7.36 vs. 6.14). QSM-based volume estimates systematically underestimated reference values, while taper-based reconstruction produced nearly unbiased estimates with an RMSE of 15.72%. Correlation analyses and PCA showed that tree architectural variables explained only a small fraction of MLS error variability. Diameter and height errors were largely independent of structural attributes, while volume errors showed moderate associations with tree size and crown density. These findings indicate that tree architecture is not a primary source of MLS measurement uncertainty. Future MLS-based forest inventory efforts should prioritize acquisition and processing optimization, as scanning conditions and forest structure appear more influential than tree shape.
Tewari, R.; Johnston, R. D.; McDonnell, J. M.; Storey, R.; Darwish, S.; Butler, J. S.; Murphy, C. M.
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Successful instrumented fusion of the lumbar spine is a complex surgical challenge, with positive patient outcomes dependent on careful surgical planning. Material selection is of critical importance to a mechanical construct supporting successful spinal fusion. Therefore, the aims of this study were to (a) evaluate the potential clinical use of finite element analysis (FEA) and (b) conduct a retrospective mechanical analysis of different implant materials in patients having undergone spinal fusion using FEA. Our methodology involved segmenting the spine from post-operative computed tomography (CT) image data from patients with previous spinal fusion. FEA models representing post-surgery cases were developed and different biomechanical loading conditions such as compression, flexion, bending and extension whilst testing pedicle screws of different materials were simulated. Patient specific finite element models were created, and biomechanical analysis were completed for all three patients. Polyetheretherketone (PEEK) constructs typically demonstrated lower peak implant stress when compared to titanium constructs for all spinal fusion levels. Furthermore, increasing the spinal fusion level resulted in significant differences in the maximum von Mises stress within both the bone and the instrumentation, whereas the 2-level fusion exhibited comparable stress levels in the bone irrespective of the instrumentation material. This pilot explores the potential of FEA as a clinical tool for assessing device and bone stresses. In our cohort, different materials can influence the stresses in both the instrumentation and the instrumented vertebrae, suggesting FEA can be useful pre- operative tool with regards to instrument selection and post-operatively to assess instrumentation and bone stresses. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=74 SRC="FIGDIR/small/742715v1_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@55959aorg.highwire.dtl.DTLVardef@d0b9d6org.highwire.dtl.DTLVardef@158c348org.highwire.dtl.DTLVardef@7ce828_HPS_FORMAT_FIGEXP M_FIG C_FIG
Brinas-Pascual, N.; Alarcon, T.; Calvo, J.; Guerrero, P.; Oliver-Bonafoux, R.
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The study of tissue dynamics has been stimulated during the last decades thanks to the use of quantitative descriptions, with the development of several theoretical and computational frameworks, many of them revolving around the notion of reaction-diffusion systems, eventually with additional structure variables beyond time and space. The use of structure variables can accommodate phenotypic traits. In this work, we study a family of competition models, where a given population depends on a resource (e.g. oxygen) and several populations are competing for it. Our quantitative description incorporates phenotypic traits and heterogeneity at the level of cell cycle variations, which influence replication rates via oxygen consumption. This enables us to replicate the fitness of specific subpopulations to environmental conditions (e.g. oxygen shortage or external influences). Using numerical simulations, we show that such models display dynamical pattern formation in the form of coupled travelling wave profiles that expand or retreat at the same wave speed. The full theoretical analysis of such dynamics is quite involved; to circumvent this difficulty, we introduce a quasi-stationary approximation for the resource dynamics. We find that this approximation can reproduce the overall behaviour very accurately, with the additional benefit of allowing theoretical treatment of the reduced model. In this way, we provide estimates on the wave speed which are numerically shown to be robust across a wide range of macroscopic parameters of the full model. The wave speeds are thus found to depend strongly on the proliferation rate of the fittest population, resembling a winner-takes-all dynamics.
Kostelnik, C. J.; Piekarska, M. L.; Sreedhar, S.; Lin, C.-Y.; Shah, A.; Gaweda, B.; Goodyke, A. J.; Xu, Y.; Balachandran, K.; Parast, L.; Bersi, M. R.; Timek, T. A.; Rausch, M. K.
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BackgroundModerate to severe tricuspid regurgitation (TR) affects approximately 1.6 million Americans, yet more than 90% of patients with significant TR remain untreated. Women exhibit higher TR prevalence and more rapid disease progression than men, but the valve-intrinsic mechanisms underlying these sex disparities remain unclear. We hypothesized that sex and circulating testosterone influence tricuspid leaflet remodeling during right-sided pressure overload. MethodsFemale, castrated male (C-Male), and non-castrated male (NC-Male) adult Dorset sheep (n = 45) underwent pulmonary artery banding (PAB) and were followed for 13 {+/-} 1.5 weeks. Tricuspid leaflets were evaluated using morphometry, 3D profilometry, biaxial mechanical testing, histology, and bulk RNA sequencing. Sex-stratified differential gene expression was performed, and pathway enrichment of key biological processes were compared between sexes. ResultsPAB produced a uniform hemodynamic stimulus and equivalent moderate-to-severe TR across sex groups. Despite similar TR burden, leaflet remodeling diverged substantially by sex and castration status. C-Males developed the broadest remodeling phenotype, characterized by diffuse multi-leaflet growth, thickening, increased nuclei count, and low-strain stiffening. Females demonstrated more restricted leaflet and region-specific structural and cellular changes, along with circumferential low-strain stiffening. NC-Males exhibited preferential septal remodeling characterized by growth, thickening, increased nuclei count, and radial high-strain stiffening. Transcriptomic analysis revealed that females upregulated a focused matricellular remodeling program enriched for extracellular space organization (67 DEGs; FDR=0.025), whereas C-Males activated coordinated extracellular matrix and apoptosis-regulatory programs (388 DEGs; FDR=0.009). In contrast, NC-Males exhibited broad transcriptional response (406 DEGs) without significant pathway enrichment. ConclusionsTricuspid leaflet maladaptation during pressure overload is sex-dependent and testosterone-sensitive, involving distinct structural, mechanical, and transcriptional remodeling programs. These findings identify sex and testosterone status as previously under-recognized modulators of tricuspid valve remodeling and may help explain clinical sex disparities in TR progression. NOVELTY AND SIGNIFICANCE What is known?O_LIPulmonary hypertension and right ventricular pressure overload are linked to tricuspid leaflet remodeling through leaflet thickening, enlargement, and altered mechanical properties. C_LIO_LISex and sex-steroid hormones regulate fibrosis and extracellular matrix remodeling in cardiovascular tissues, but their role in tricuspid leaflet remodeling remains poorly understood. C_LI What new information does this article contribute?O_LISex and circulating testosterone status influence the magnitude, spatial distribution, biomechanical behavior, and transcriptional organization of tricuspid leaflet remodeling during pressure overload. C_LIO_LIFemales, castrated males, and non-castrated males develop distinct remodeling programs characterized by focused matricellular remodeling, coordinated extracellular matrix/apoptosis signaling, and diffuse transcriptional activation, respectively. C_LIO_LIThese findings identify sex and hormonal status as biological regulators of tricuspid valve maladaptation during functional tricuspid regurgitation. C_LI SummarySex differences in tricuspid regurgitation progression are recognized clinically, yet the mechanobiological basis underlying these disparities remains poorly understood. Using a controlled ovine model of pressure overload-induced secondary tricuspid regurgitation, we demonstrated that tricuspid leaflet maladaptation is a sex-specific and testosterone-sensitive process spanning structural, mechanical, and transcriptional scales. Under comparable hemodynamic overload, all animals developed significant tricuspid regurgitation, but leaflet remodeling patterns diverged substantially across sexes. Castrated male sheep exhibited the broadest maladaptive phenotype, characterized by diffuse multi-leaflet growth and thickening, increased low-stretch stiffness, and coordinated extracellular matrix and apoptosis-regulatory transcriptional programs. Female sheep developed more spatially restricted remodeling accompanied by a focused matricellular and extracellular matrix secretory response, whereas non-castrated male sheep demonstrated selective leaflet remodeling with broad, but less coordinated, transcriptional activation. Different remodeling patterns emerged in females and castrated males despite comparable testosterone levels, suggesting that testosterone depletion alone does not fully explain these tricuspid valve remodeling phenotypes. These findings establish sex and testosterone status as previously underrecognized biological regulators of tricuspid leaflet maladaptation and support the emerging view that valve leaflets are active, mechanobiologically responsive, participants in functional tricuspid regurgitation progression.
Mazzi, V.; Gallo, D.; Natarajan, T.; Schollenberger, J.; Calo, K.; Saloner, D.; Steinman, D. A.; Morbiducci, U.
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Cerebral aneurysms are abnormal outpouchings of arteries within the brain and occur in [~]1 in 30 adults. Their initiation, growth, and rupture have been linked to focal blood flow abnormalities--often termed "disturbed" or "hostile" hemodynamics--but commonly-used hemodynamic metrics yield conflicting associations with pathology and lack a unifying mechanistic interpretation. Building on a theoretically-grounded link between wall shear stress and near-wall vorticity, we hypothesized that a topology-based description of near-wall flow can operationalize the concept of hostile hemodynamics in a reproducible way. Inspired by atmospheric tornadic phenomena, we sought a principled taxonomy of coherent near-wall fluid structures with potential mechanobiological and clinical implications. Using high-fidelity computational fluid dynamics simulations in anatomically realistic geometries, we identified coherent near-wall fluid structures whose organization mirrors well-studied atmospheric phenomena: tornado-like columnar rotating cores; downburst-like nonrotating wall-impinging jets with tangential outflow, roll-cloud-like tangential vortices; and mixed configurations. These tornadic events on the aneurysm luminal surface were identified from wall shear stress topology, consistent with its theoretical connection to near-wall vorticity kinematics. The presence of tornadic phenomena--and their imprints on the aneurysm wall--was independently observed in vivo using 4D flow magnetic resonance imaging. By translating concepts from atmospheric physics into vascular biomechanics, this topology-based framework yields a unified mechanistic language for describing near-wall hemodynamics, resolving blood flow complexity into interpretable and reproducible coherent fluid structures, enabling standardized hemodynamic phenotyping, and supporting hypothesis-driven studies of aneurysms and other cardiovascular diseases where greater fluid-mechanical specificity and interpretability may strengthen links between mechanobiology and clinical risk.
Hayashi, Y.; Ujihara, Y.; Nakamura, M.; Sugita, S.
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BackgroundCardiovascular disease risk is higher in men than in women. Although sex differences in aortic wall adaptation following antihypertensive treatment have been reported in acute hypertension models, the response after gradually developing hypertension, which mimics human essential hypertension, remains unclear. This study investigated sex differences in aortic wall adaptation following acute blood pressure reduction after gradually developing hypertension. MethodSeventeen-week-old spontaneously hypertensive rats (SHRs) were assigned to the Hypertensive group or the antihypertensive (Reversal) group (N = 5/sex each). The Reversal group received the antihypertensive drug captopril for 4 weeks to maintain systolic blood pressure below 130 mmHg. Age-matched Wistar Kyoto rats (N = 3/sex) served as normotensive (Normal) group. After the experimental period, arterial wall thickness, circumferential wall stress, smooth muscle cell phenotype, and histological changes were evaluated. ResultsAntihypertensive treatment significantly reduced systolic blood pressure in both sexes. Both male and female SHRs exhibited elevated circumferential wall stress during the gradual development of hypertension. In females, antihypertensive treatment significantly reduced medial thickness compared with the Hypertensive group, whereas males showed no reduction. Circumferential wall stress in female Reversal group did not differ significantly from either the Hypertensive or Normal group, whereas males exhibited a significant reduction in circumferential wall stress compared with the Hypertensive group. Furthermore, the reduced collagen area fraction in the Hypertensive group returned to the normotensive levels only in females following antihypertensive treatment. ConclusionThese findings indicate that vascular remodeling induced by gradually developing hypertension is more effectively reversed by antihypertensive treatment in females than in males.
Hickey, J. W.; Chan, E. Y. K.; Evans, L. J.; O'Brien, W. T.; Xie, B.; Roberts, S. S. H.; Butler, S. E.; Ernst, J.; Zhou, W. J. Q.; Zimmerman, K. A.; Spitz, G.; Parker, T. D.; O'Brien, T. J.; Shultz, S. R.; Sharp, D. J.; Ghajari, M.; McDonald, S. J.
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Purpose: Identifying head impacts linked to brain injury in sport remains challenging. Instrumented mouthguards quantify head-impact kinematics, and finite element (FE) modelling can transform these data into brain strain estimates, which may better reflect injury risk than kinematics alone. Here, we examined associations between mouthguard-measured kinematics, FE-derived strain, and plasma brain injury biomarker GFAP following head impacts. Methods: We analysed 41 video-verified impacts from male Australian football players, including 22 assessed for concussion (17 diagnosed) and 19 unassessed. Instrumented mouthguards recorded peak linear acceleration (PLA), peak rotational acceleration, and peak rotational velocity (PRV). Brain strain was estimated using the Imperial College FE brain model, and plasma GFAP was quantified using Simoa. Biomechanical-GFAP associations were examined using Spearman correlations and segmented regression. Results: For impacts overall, plasma GFAP was moderately correlated with PLA ({rho}=0.46, 95% CI: 0.20-0.66), PRV ({rho}=0.53, 95% CI: 0.20-0.78), and strain ({rho}=0.60, 95% CI: 0.32-0.80). Associations were stronger within concussion cases for strain ({rho}=0.86, 95% CI: 0.58-0.97) and PRV ({rho}=0.64, 95% CI: 0.15-0.93). Piecewise regression identified strain levels above which strain-GFAP relationships steepened across the whole-brain and brainstem. In concussion cases, supra-threshold brainstem strain was associated with greater symptoms. Conclusion: Finite element brain strain may better predict brain injury risk following a sport-related head impact than peak acceleration metrics. Stronger associations with plasma GFAP, particularly among concussion cases, and evidence of a biomechanical threshold, support the use of biomarker-informed strain measures in future risk modelling and the development of brain injury screening thresholds.
Rodriguez Ferrante, G. O.; Dasika, N. s.; Nam, A.; Lu, J.; Tumber, N.; Kully-Rivera, E.; Klei, V.; Zhang, D.; Romero, M. E.; de la Iglesia, H. O.
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The U.S. House's approval of the Sunshine Protection Act has revived the debate over permanent daylight saving time (DST) versus permanent standard time (ST). Health and sleep organizations favor permanent ST because it benefits health, especially for children with rigid school schedules. Further, permanent DST would push school start times to before sunrise in many regions, leading to dark-morning commutes. However, the safety consequences of this shift remain unquantified. Using real school start times for 14 states that have enacted permanent DST legislation, together with local sunrise time, we counted the school days on which students must leave home before sunrise under permanent ST, the current system, and permanent DST. In Washington State, where schools start on average at 08:27, neither permanent ST nor the current system requires any pre-sunrise departure, whereas permanent DST would for most of the winter. Using real school start-time data, permanent DST would add about 35 million child-days of pre-sunrise travel in Washington alone relative to the current system, with similar patterns across the other 13 states. Extrapolated to all U.S. public schools and assuming an 8:00 departure, permanent DST would generate more than 2 billion additional dark-morning commutes each year relative to the current system. Finally, analyzing Seattle traffic collisions, we found that the odds that a crash involved a pedestrian were 143% higher on dark mornings (adjusted odds ratio 2.4). Permanent DST would therefore expose many more children, on many more days, to elevated pedestrian-crash risk, evidence that deserves consideration as the United States chooses a time standard.
Owolabi, R. O.; Martcheva, M.; Ghosh, I.
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Human Papillomavirus (HPV) infection among men who have sex with men (MSM) has become a significant public health concern, particularly in countries where male vaccination is unavailable. Given the high susceptibility of MSM to HPV and anal cancer, and the unavailability of HPV vaccination for males in low- and middle-income countries (LMICs), there is a need to identify alternative interventions for reducing disease transmission and burden in this population. The novel mathematical model presented in this article couples smoking behavior dynamics with HPV transmission and anal cancer progression among MSM. Smoking reduction is introduced as an intervention to assess its effects on disease transmission and burden. The basic reproduction number (R0) is derived using the next-generation matrix method, and a global sensitivity analysis is performed using partial rank correlation coefficients (PRCC) to identify the influence of model parameters on RR0. Further, the theoretical analysis of the model reveals a backward bifurcation, implying that RR0 < 1 is necessary but not sufficient to eradicate the disease. The study finds that smoking reduction among MSM reduces HPV infection and anal cancer burden relative to baseline projections without intervention. The joint effect of smoking reduction and vaccination shows that the critical vaccination coverage needed to achieve RR0 <1 decreases as the level of smoking reduction increases. A similar outcome is observed for contact reduction. These findings highlight the importance of concurrent interventions, which can significantly curtail the spread of HPV and reduce disease burden in both the high-risk group and the general population.