Biomechanics and Modeling in Mechanobiology

Adolescent idiopathic scoliosis (AIS) alters spinal geometry and may influence the biomechanical response of the spine during functional postures. However, posture-dependent changes in spinal loading and paraspinal muscle forces in AIS remain poorly understood. This study investigated the effects of trunk posture on intervertebral loading and paraspinal muscle forces using a subject-specific musculoskeletal model of an adolescent with AIS. The spinal deformity was reconstructed from biplanar radiographs and incorporated into a full-body musculoskeletal model. Flexion, extension, lateral bending, and axial rotation were simulated at three incremental magnitudes, with motion distributed across the thoracolumbar spine. Intervertebral compressive and lateral forces around the curve apex and forces in the erector spinae (ES) and multifidus (MF) muscles were evaluated. Trunk flexion produced the greatest compressive loading, reaching 337 N at the curve apex and 372 N two levels below the apex at 30{degrees} flexion. Lateral bending produced pronounced direction-dependent loading: concave-side bending increased lateral forces, whereas convex-side bending increased compressive forces. Axial rotation produced similar but smaller direction-dependent changes. Paraspinal muscle forces were consistently asymmetric, with concave-side dominance of the ES and convex-side dominance of the MF. Flexion and convex-sided movements generally produced greater muscle imbalance, while increasing posture magnitude amplified spinal loading and muscle forces. These findings demonstrate that trunk posture, movement direction, and magnitude substantially influence the biomechanical environment of the scoliotic spine and should be considered when evaluating spinal mechanics in AIS.

Endothelial dysfunction is a hallmark of numerous vascular pathologies and is strongly influenced by mechanobiological forces within the vascular microenvironment. While the effects of shear stress have been extensively investigated, the mechanisms by which elevated hydrostatic pressure regulates endothelial junctional organisation remain sparsely investigated. Here, we employed a microfluidic platform to investigate the combined effects of low shear stress (1.4 dyne/cm2) and elevated hydrostatic pressure (~3972 Pa) on endothelial junctional dynamics. Elevated hydrostatic pressure induced marked remodelling of VE-cadherin junctions, characterised by formation of serrated, finger-like structures accompanied by increased YAP1 nuclear localisation and reduced YAP1-VE-cadherin cytoplasmic colocalisation compared to shear stress alone conditions. Further, elevated hydrostatic pressure also demonstrated an increase in cytoplasmic accumulation of EPS8, an actin adaptor protein, and increased cytoplasmic EPS8-VE-cadherin colocalisation. These observations were accompanied by functional changes marked by increased endothelial permeability, and enhanced THP-1 monocyte adhesion, thus suggesting activation of mechanosensitive pathways linked to dynamic junctional reorganisation. Inhibition of PI3K at elevated hydrostatic pressure exhibited a thin VE-cadherin patterning and increased cytoplasmic EPS8-VE-cadherin colocalisation, thus demonstrating a prominent role for PI3K signalling in regulating the junction organisation. Interestingly, Piezo-1 activation using Yoda1 produced context-dependent effects. Under shear stress alone, Yoda1 promoted YAP1 nuclear translocation, reduced YAP1-VE-cadherin colocalisation, increased endothelial permeability but strikingly did not impact THP-1 adhesion compared to shear stress alone conditions. In contrast, under elevated hydrostatic pressure conditions, Yoda1 significantly reduced both endothelial permeability and THP-1 adhesion while increasing YAP1-VE-cadherin colocalisation and decreasing YAP1 nuclear accumulation. Collectively, these findings identify a previously underappreciated elevated hydrostatic pressure-Piezo-1-PI3K signalling axis that regulates endothelial barrier integrity and pro-adhesive endothelial activation through coordinated regulation of VE-cadherin, YAP1, and EPS8. These results highlight elevated hydrostatic pressure as a unique mechanobiological stimulus, distinct from that of shear stress alone and provide novel insights into mechanisms underlying microvascular dysfunction.

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.

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.

Muscle architecture shapes muscle function and changes with age, growth, training and disease, yet quantifying three-dimensional (3D) muscle architecture in vivo remains challenging. We introduce a hybrid fascicle tractography approach for freehand 3D ultrasound data that accurately reconstructs 3D muscle fascicles with respect to an objective, anatomically relevant coordinate system defined by the muscle's central aponeurosis. The hybrid approach combines Hessian-based fascicle detection with wavelet-based refinement to generate volumetric fascicle orientations. In a synthetic dataset with known ground truth, fascicle orientations and lengths were estimated with errors of [≤]2{degrees} and ~1.5%, respectively. In vivo, the approach detected physiologically plausible fascicle lengthening in the human tibialis anterior following a passive plantar flexion rotation, whereas diffusion tensor imaging of the same muscle did not. The proposed method enables anatomically relevant, objective and non-invasive quantification of 3D muscle architecture in vivo, providing a practical framework for applications in clinical and applied muscle physiology.

Focal adhesions maintain force-bearing attachment between cells and the extracellular matrix but can also undergo dynamic remodeling. Their assembly and actomyosin tension are coupled through mechanochemical feedback. The processes underlying this feedback are not instantaneous and therefore involve a time delay. However, how this delayed feedback gives rise to stable adhesion maintenance or dynamic remodeling remains unclear. Here, paired time-lapse measurements of vinculin fluorescence and traction stress revealed distinct local adhesion-force dynamics, including low-fluctuation and recurrent fluctuation patterns. To examine how these patterns could arise, we formulated a minimal mechanochemical model coupling focal adhesion assembly and actomyosin force through delayed reciprocal feedback. The model exhibited stable and oscillatory modes depending on feedback strength, the balance of opposing feedback effects, and the effective feedback delay. Bistability and hysteretic switching also occurred in a subset of parameter space, and the oscillation period followed a power-law relation with the delay. These results suggest that stable adhesion maintenance and dynamic remodeling can emerge from a common mechanochemical feedback architecture.

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.

The erythrocyte sedimentation rate (ESR) is one of the most common and widely used laboratory diagnostic parameters in connection with inflammatory reactions and it is probable that every reader has already experienced a determination of their ESR. A rapid ESR is a non-specific parameter that provides information about the inflammatory process. Although the origins of this methodology date back to antiquity, the description of the process as the collapse of a percolating gel formed from erythrocytes has only recently been achieved. It was not yet known whether slow ESR has any medically relevant significance. Here we show a variety of clinical pictures that exhibit a systematically slow ESR (e.g., sickle cell disease, neuroacanthocytosis syndromes, chronic mountain sickness). Using a combination of measured data and physical modelling, we show how the accuracy and significance of ESR data can be increased. With this improved ESR (supraESR), we introduce a completely new, cost-effective diagnostic parameter, based on an established and easily automated measurement method, that enables low-cost screening for neuroacanthocytosis syndrome, a group of rare neurodegenerative diseases previously detectable only through complex diagnostic tests.

Abstract Calcific deposits in the arterial media have been associated with a number of metabolic and genetic disorders including diabetes, chronic kidney disease and generalized arterial calcification of infancy. While medial calcification and physiologic hard tissue mineralization in the skeleton are both regulated by several common determinants, emerging data suggest that there might be fundamental differences in the mechanisms underlying these two processes. Objective: We previously demonstrated that elastin haploinsufficiency delays medial calcification in MGP-deficient mice. Here, using mice in which a human ELN transgene rescues mouse elastin deficiency, we investigated whether the origin and abundance of arterial elastin differentially affect the initiation and progression of medial calcification. Approach and Results: We pursued a transgenic approach to alter the arterial elastin scaffold in MGP-deficient mice. Our analyses of a humanized MGP-deficient model with 40% reduction of medial elastin content showed a complete absence of the early-stage vascular calcification. Additionally, we showed that mouse and human elastin orthologues affect vascular calcification in a comparable manner. Conclusion: Arterial elastin abundance, rather than orthologue origin, modulates the initiation and progression of medial calcification in MGP-deficient mice. A further reduction in arterial elastin beyond that achieved by elastin haploinsufficiency profoundly delays mineral deposition and maturation, whereas restoration of elastin abundance through transgenic human ELN expression restores arterial calcification.

Coronary flow waveforms have a distinct diastolic-dominant shape with periods of low or retrograde flow during systole. While the general waveform shape has been attributed to complex interactions between cardiac and vascular mechanics, there is limited research into the variability in coronary flow waveforms and what this variability may reveal about cardiac function. This work presents a shape analysis of left anterior descending artery (LAD) flow waveforms using Fourier transforms and Singular Value Decomposition (SVD) performed on baseline data collected from 32 pigs. Pigs included in the study reflect two breeds (Ossabaw and Yorkshire) and three different experimental conditions (lean-control, lean-paced, and obese-paced). Fourier transforms were used to decompose the waveforms into 15 harmonics for each pig. An SVD analysis is then used to extract temporal patterns of the waveforms. Correlations between pig-specific coefficients for the SVD modes and clinical metrics were used to investigate physiological explanations of LAD waveform variability. Temporal LAD flow patterns of the second SVD mode are significantly correlated with heart rate. The third SVD mode significantly correlates with mean blood pressure and maximum hyperemic flow. Furthermore, the fourth SVD mode is weakly correlated with left-ventricular end diastolic pressure and endocardial-epicardial flow ratios. This work demonstrates that LAD flow waveforms can be broken down into temporal patterns that correlate with physiological features. Furthermore, this shape-analysis method allows for waveform reconstruction and simplifies visualization of the temporal patterns identified using SVD, an advantage over existing methods that focus on characterizing flow waveforms by points of interest.

Low-density lipoprotein (LDL) is a major atherogenic lipoprotein, yet its potential to directly modify the fibrin scaffold of blood clots is incompletely understood. Here, we investigated how LDL alters plasma fibrin network architecture and internal fibrinolysis across defined fibrinogen/thrombin conditions. Pooled normal human plasma was supplemented with LDL and clotted with controlled concentrations of fibrinogen and thrombin. Fibrin architecture was visualized by confocal microscopy and quantified by pore-size analysis; clot formation and lysis were monitored turbidimetrically in the presence of tissue plasminogen activator (tPA). Increasing LDL produced a pronounced reduction in fibrin-network pore size across the tested fibrinogen/thrombin conditions. The LDL dependence of pore diameter was well described by a power-law relationship, D_pore=(6.54 +/- 0.11)[LDL]^(-0.12 +/- 0.02) , (R^2 = 0.90), with a significant negative LDL exponent (p = 4 x 10^5). Increasing LDL also prolonged clot lysis time and altered turbidity kinetics. These findings extend epidemiologic and clinical associations between ApoB-containing lipoproteins and hypofibrinolytic clot phenotypes by demonstrating, in a controlled plasma system, that LDL itself can modify fibrin network architecture and fibrinolytic susceptibility. The results support a structure-function role for LDL within the fibrin biomaterial and motivate direct tests of LDL incorporation, protofibril packing, fibrinolytic-protein binding, and single-fiber mechanics.

Three-dimensional (3D) mural cell morphology is heterogeneous and coupled to vessel geometry, however, measurements from two-dimensional (2D) maximum intensity projections (MIP) obscure overlapping processes and cell-vessel contacts. Accordingly, we developed Mural-VISTA, a semi-automated Python workflow for mural cell-vessel interaction and single-cell topo-morphology analysis of reconstructed surface meshes. This workflow integrates mesh pretreatment, interactive centerline extraction, hierarchical segmentation of cell soma, main axis and secondary processes (branches), and extraction of 36 multiscale (cell process segment level, process level, and whole cell level) topo-morphological and vessel-referenced metrics. Mural-VISTA identified morphological changes in pericytes and vascular smooth muscle cells (vSMCs) with altered RhoA activity. Constitutive active RhoA (RhoA CA) over-expression reduced branch complexity and increased process alignment in both cell types, while increased whole-cell and branch solidity only in vSMCs. Dominant negative RhoA (RhoA DN) over-expression increased branch abundance and reduced branch solidity in pericytes but not vSMCs, suggesting cell-type specific effect of reduced RhoA activity. In conclusion, Mural-VISTA enables quantitative 3D profiling of mural cell architecture and its spatial relationship with the vessel.

This study aimed to (1) develop an elasticity framework for the sprint force-velocity (F-V) relationship and (2) examine how maximal force (F_{0}), maximal velocity (v_{0}), and sprint distance modulate the four derived elasticity metrics, and (3) explore these elasticity metrics' interrelation. After modelling the F-V relationship differential equation, four elasticity metrics were defined as force elasticity (F_{e}), the elasticity of sprint time to F_{0}; velocity elasticity (v_{e}), the elasticity of sprint time to v_{0}; the force-velocity elasticity norm {(\mathrm{F}-\mathrm{V}}_{\mathrm{EN}}=\sqrt{F_{e}^{2}+v_{e}^{2}}), capturing the combined sprint time sensitivity to proportional changes in F_{0} and v_{0}; and the force-velocity elasticity ratio {(\mathrm{F}-\mathrm{V}}_{\mathrm{ER}}=F_{e}{\div v}_{e}), indicating which variable dominates the sprint time response. Model simulations showed that F_{e} decreased with rising F_{0} and increased with rising v_{0}, while v_{e} showed the opposite pattern. With increasing sprint distance, F_{e} decreased and v_{e} increased. Given its negligible effect on sprint time, ignoring air resistance yields a conservation law (2F_{e}+v_{e}\equiv 1), indicating that a gain in one elasticity metric necessarily diminishes the other in a fixed proportion. This framework also identifies a valley distance (d_{valley}) at {\mathrm{F}-\mathrm{V}}_{\mathrm{ER}}=2, where {\mathrm{F}-\mathrm{V}}_{\mathrm{EN}} is minimized (\sqrt{0.2}) and sprint time is least responsive to changes in F-V relationship variables. Empirical data confirmed that the two theoretical laws still hold approximately when air resistance is considered. By linking changes in F_{0} and v_{0} to sprint time across different distances, the elasticity framework provides a quantitative basis for estimating the theoretical sprint time response to documented changes in F-V relationship variables.

Communities exposed to flooding can experience markedly different mental health outcomes, yet conventional resilience indicators capture only part of the social and contextual conditions that may explain this variation. This study develops a multilevel and predictive framework for examining community resilience and depressive symptoms following flood exposure in Indonesia. Data were drawn from 20,303 respondents aged 15 years and older nested within 312 communities in the Indonesia Family Life Survey (IFLS-5). Depressive symptoms were assessed using the 10-item Centre for Epidemiologic Studies Depression Scale (CES-D-10), with Rasch Partial Credit Model calibration used to examine measurement properties. Bayesian multilevel models quantified between-community heterogeneity and assessed how far observable structural resources accounted for this variation. Community resilience was represented through two complementary constructs: structural resilience, based on observable socioeconomic and social-capital resources, and Latent Community Protective Capacity (LCPC), a model-derived proxy for residual contextual variation in depressive-symptom risk. Approximately 6 percent of variation was attributable to between-community differences, while observable structural resources explained only part of this heterogeneity. Structural resilience and LCPC were weakly correlated (r = 0.155). Moderation analyses provided no clear evidence that structural resilience altered the flood-depression association, while LCPC showed a directionally consistent but uncertain buffering pattern. Predictive models incorporating community-level information improved discrimination, with the best-performing model reaching an ROC-AUC of approximately 0.71. The findings suggest that observable resource-based indices provide an incomplete account of community-level mental health vulnerability and that residual contextual measures may provide complementary information, while requiring cautious interpretation and independent validation.

The ocean tides influence key Earth system processes at a range of spatial and temporal scales. It is known that the geometry of ocean basins is the leading controller of tidal energetics, so well-constrained palaeogeographic reconstructions and tidal properties for Earths past are imperative when investigating other Earth system processes. Here, we present a novel way to constrain both deep-time tidal model results and reconstructions, by combining palaeoecology with sedimentology. We compare new palaeo-tidal model simulations for the Cambrian period, significant for the early origin and radiation of major animal fauna, to tidal proxies. One of the most abundant soft-bodied organisms preserved during this time are cnidarian medusae (jellyfish). A total of 17 cnidarian medusae localities were obtained through the literature, which had an adequate global distribution and occurred at regular intervals throughout the period of study. In some locations there were also estimates of palaeo-tidal range. Our results show a good agreement between the simulations and proxy data. In the few locations where there is disagreement, it is proposed that the palaeogeographic reconstructions are missing details, e.g., island chains, and our results allow for the palaeogeographic reconstructions to be improved. The proxy method presented is promising and can be applied to other time-periods with different marine fossils, particularly at evolutionary and extinction periods where the marginal marine environment is of importance.

Rib-cage morphology is a determinant of thoracic biomechanics, ventilation, and injury response, yet statistical shape models (SSMs) of the rib cage have relied on small cohorts (~100s of individuals) imaged by clinical computed tomography, which over-represents injury and disease. We constructed a surface-based SSM of the complete 24-rib cage from 26,275 standardised whole-body magnetic resonance imaging (MRI) scans of adults aged 19-74 years from the population-based German National Cohort (NAKO). Ribs were segmented with a deep-learning pipeline (a rib-extended SPINEPS model), reconstructed as per-rib surface meshes, and brought into dense vertex-wise correspondence by Gaussian-process morphable registration in Scalismo; the aligned ensemble was summarised by generalised Procrustes analysis and principal component analysis (PCA). Fourteen per-rib geometric descriptors provided a quantitative cross-walk between the abstract PCA modes and named shape features, and associations with sex, age, body size and composition (including body-fat percentage), and smoking exposure were estimated by multivariable regression with Benjamini-Hochberg false-discovery-rate control. Shape variation was strongly concentrated: 28 modes captured 95% of the total variance, and the first three alone accounted for 69.4% (PC1, 42.6%; PC2, 16.3%; PC3, 10.5%) and admitted consistent anatomical readings - a sexually dimorphic axis (PC1), a slender-versus-stout body-habitus contrast (PC2), and a free-rib-size axis at ribs 11-12 (PC3). The sexes were nearly fully separated along PC1 (Cohen's d = 2.52). Body mass and body-fat percentage were the dominant modifiable correlates of rib-cage shape, whereas the association with cumulative smoking exposure was comparatively small. The model is released as a population-representative geometric reference for benchmarking and morphing donor-derived finite-element human-body models and for further large-cohort shape analysis.

Thoracic aortic aneurysm and dissection (TAAD) is a life-threatening disease characterized by progressive medial degeneration, impaired mechanical integrity, and extracellular matrix (ECM) degradation. However, no pharmacological therapy has been proven to halt aneurysm progression or prevent dissection or rupture. Vascular smooth muscle cells (VSMCs) are vital for maintaining medial architecture by sensing and remodeling the surrounding ECM; however, the mechanism by which abnormal ECM mechanics are transmitted to nuclear transcriptional programs that disrupt aortic wall matrix homeostasis remains incompletely understood. Integrative transcriptomic screening of Lysyl oxidase (LOX)-deficient and ?-aminopropionitrile (BAPN)-induced TAAD models identified vestigial-like family member 4 (VGLL4) as a mechanosensitive transcriptional regulator of TAAD. VGLL4 was enriched in VSMCs and markedly increased in aortas from patients with TAAD and BAPN-induced TAAD mice. VSMC specific deletion of Vgll4 protected mice from BAPN-induced aortic dilation, dissection, rupture-associated mortality, vascular stiffening, ECM degradation, and medial destruction. Mechanistically, pathological matrix remodeling and mechanical stress induced VGLL4 expression in VSMCs, where VGLL4 cooperated with specificity protein 1 (SP1) to activate Wisp1 transcription. In vivo, VSMC-enriched Wnt-inducible signaling pathway protein (WISP1) overexpression exacerbated TAAD progression, whereas Wisp1 knockdown protected against BAPN-induced TAAD and mitigated the severe aortic phenotype driven by VGLL4 overexpression. Secreted WISP1 bound Tissue Inhibitor of Metalloproteinases 3 (TIMP3) through its C-terminal domain and impaired TIMP3-mediated MMP9 inhibition, thereby increasing MMP9 proteolytic activity and accelerating ECM degradation. Consistently, in vivo Wisp1 knockdown protected against BAPN-induced TAAD. Together, these findings define the VGLL4-WISP1-TIMP3/MMP9 axis, which couples pathological ECM mechanics to nuclear transcriptional activation and protease-dependent matrix degradation in VSMCs. This pathway promotes medial structural failure, aortic mechanical stability loss, and TAAD progression, identifying WISP1 as a potential therapeutic target for preserving aortic wall matrix homeostasis.

Background: Newly available arm angle data offers a new dimension to understand rising rates of arm injury in MLB pitchers. Purpose: To evaluate the relationship between arm angle, pitch characteristics, and elbow and forearm injury in MLB pitchers.<br><br> Study Design: Retrospective cohort study; Level of evidence, 3 Methods: Statcast data from 2020 to 2025 and MLB injured list (IL) data were used to evaluate arm angle and pitch characteristics in relation to elbow and forearm injuries. Results are presented with and without requirements on prior season workload and for same-season and next-season injury incidence. A generalized additive model (GAM) was used to capture non-linear dependence and interactions between selected features and injury incidence to the elbow or forearm. Average marginal effect (AME) odds ratios are reported for main effect terms. Results: N = 3,812 pitcher-seasons were included. 29% pitchers who underwent UCLR did so in the same season as a forearm injury (tmean=44, tmedian=27 days to surgery). Arm angle, fastball usage, and their interaction were the three most predictive features. Arm angle was positively related to incidence of injury (ORmeanAME=1.014), fastball usage was inversely related to incidence of injury (ORmeanAME=0.243), and arm angle moderated the effect fastball usage at high arm angle, where increased usage was no longer protective. Slider velocity (ORmeanAME=1.072), spin rate (ORmeanAME=1.001), and usage (ORmeanAME=2.039) also significantly predicted injury risk. Fastball velocity was not significant in any fit, with ORmeanAME=0.999 across all fits. Fit-level Nagelkerke R2 values ranged from .019 to .052. Conclusion: Fastball usage and arm angle, not velocity, predicted elbow and forearm injury risk among MLB pitchers, and arm angle was the single most predictive feature. The heterogeneity of risk factors as a function of arm angle, and the novelty of MLB arm angle data, may explain why fastball usage has been previously underexplored as a risk factor. Keywords: baseball; arm angle; fastball velocity; fastball usage; spin rate; UCL; ulnar collateral ligament; elbow injury; forearm injury; Statcast

Background: Lumbar disc herniation, with or without concomitant disc degeneration, is a major cause of lumbar radiculopathy and low back pain, which also a key public musculoskeletal disorder without an exact pathophysiology. Studies have suggested that inflammatory cells and biochemical markers of inflammation also play an important role in lumbar radiculopathy in addition to nerve compression. The aim of the present study was to assess the association of selected circulatory inflammatory markers (CRP, hs-CRP and E-selectin) in patients with lumbar disc herniation without radiological degeneration (LDH) and lumbar disc herniation with radiological degeneration (LDHD). Materials & methods: This case-control study included 208 participants, comprising 104 patients with lumbar disc pathology and 104 controls. Patients were further stratified into LDH (n=67) and LDHD (n=37). Serum CRP, hs-CRP and E-selectin concentrations were measured. Results: Among the patients, 35.6 % presented with LDHD while 64.4 % had only LDH. Significantly increased median hs-CRP (p<0.001) and CRP (p<0.001) were observed in patients groups compared to controls, while CRP showing a consistent independent association across the combined disease (OR=1.68, 95% CI=1.33-2.14, p<0.001), LDHD (OR=1.62, 95% CI=1.16-2.20, p=0.005) and LDH (OR=1.69, 95% CI=1.30-2.20, p<0.001) multivariable models. No significant difference was observed in serum E-selectin between the study groups. Multivariable models incorporating inflammatory and clinical variables demonstrated substantially greater discriminatory performance than individual biomarkers alone. Conclusion: Elevated circulating CRP and hs-CRP concentrations were associated with lumbar disc pathology, with CRP showing a consistent independent association across the combined disease, LDH and LDHD multivariable models, whereas E-selectin showed no significant association. Multivariable models incorporating inflammatory and clinical variables demonstrated greater discriminatory performance than individual biomarkers. These findings support a potential systemic inflammatory component in lumbar disc pathology, although the cross-sectional nature of the measurements does not establish causality or a local inflammatory response within the disc.

Mechanisms shaping population vulnerability to typhoon-related mortality remain poorly understood. Constructing a Bayesian spatio-temporal model, we linked 12.9 million deaths across Japan from 2010 to 2019 to population-weighted typhoon wind exposure and assessed effect modification by income, natural hazard vulnerability and healthcare access. Typhoon exposure was associated with 2,426 cumulative excess deaths [95% credible interval: 139, 4,632] among adults [&ge;]70 years, with mortality increasing within 0-1 weeks of exposure and more strongly in areas with limited healthcare access and greater hazard vulnerability. Among individuals <70 years, cumulative excess mortality was uncertain [781 deaths; -309 to 1,900], but delayed mortality increases were concentrated in lower-income and landslide-prone areas. These distinct patterns suggest that typhoon mortality reflects an interaction between acute exposure, demographic ageing and geographically uneven adaptive capacity, highlighting the need to incorporate local vulnerability into climate-resilient health systems.