Browsing by Author "Lewis, Valerae O."

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    A computational method for estimating trunk muscle activations during gait using lower extremity muscle synergies
    (Frontiers Media S.A., 2022) Li, Geng; Ao, Di; Vega, Marleny M.; Shourijeh, Mohammad S.; Zandiyeh, Payam; Chang, Shuo-Hsiu; Lewis, Valerae O.; Dunbar, Nicholas J.; Babazadeh-Naseri, Ata; Baines, Andrew J.; Fregly, Benjamin J.; Rice Computational Neuromechanics Laboratory
    One of the surgical treatments for pelvic sarcoma is the restoration of hip function with a custom pelvic prosthesis after cancerous tumor removal. The orthopedic oncologist and orthopedic implant company must make numerous often subjective decisions regarding the design of the pelvic surgery and custom pelvic prosthesis. Using personalized musculoskeletal computer models to predict post-surgery walking function and custom pelvic prosthesis loading is an emerging method for making surgical and custom prosthesis design decisions in a more objective manner. Such predictions would necessitate the estimation of forces generated by muscles spanning the lower trunk and all joints of the lower extremities. However, estimating trunk and leg muscle forces simultaneously during walking based on electromyography (EMG) data remains challenging due to the limited number of EMG channels typically used for measurement of leg muscle activity. This study developed a computational method for estimating unmeasured trunk muscle activations during walking using lower extremity muscle synergies. To facilitate the calibration of an EMG-driven model and the estimation of leg muscle activations, EMG data were collected from each leg. Using non-negative matrix factorization, muscle synergies were extracted from activations of leg muscles. On the basis of previous studies, it was hypothesized that the time-varying synergy activations were shared between the trunk and leg muscles. The synergy weights required to reconstruct the trunk muscle activations were determined through optimization. The accuracy of the synergy-based method was dependent on the number of synergies and optimization formulation. With seven synergies and an increased level of activation minimization, the estimated activations of the erector spinae were strongly correlated with their measured activity. This study created a custom full-body model by combining two existing musculoskeletal models. The model was further modified and heavily personalized to represent various aspects of the pelvic sarcoma patient, all of which contributed to the estimation of trunk muscle activations. This proposed method can facilitate the prediction of post-surgery walking function and pelvic prosthesis loading, as well as provide objective evaluations for surgical and prosthesis design decisions.
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    BIGH3 mediates apoptosis and gap junction failure in osteocytes during renal cell carcinoma bone metastasis progression
    (Elsevier, 2024) Pan, Tianhong; Liu, Fengshuo; Hao, Xiaoxin; Wang, Shubo; Wasi, Murtaza; Song, Jian H.; Lewis, Valerae O.; Lin, Patrick P.; Moon, Bryan; Bird, Justin E.; Panaretakis, Theocharis; Lin, Sue-Hwa; Wu, Danielle; Farach-Carson, Mary C.; Wang, Liyun; Zhang, Ningyan; An, Zhiqiang; Zhang, Xiang H. -F.; Satcher, Robert L.
    Renal cell carcinoma (RCC) bone metastatis progression is driven by crosstalk between tumor cells and the bone microenvironment, which includes osteoblasts, osteoclasts, and osteocytes. RCC bone metastases (RCCBM) are predominantly osteolytic and resistant to antiresorptive therapy. The molecular mechanisms underlying pathologic osteolysis and disruption of bone homeostasis remain incompletely understood. We previously reported that BIGH3/TGFBI (transforming growth factor-beta-induced protein ig-h3, shortened to BIGH3 henceforth) secreted by colonizing RCC cells drives osteolysis by inhibiting osteoblast differentiation, impairing healing of osteolytic lesions, which is reversible with osteoanabolic agents. Here, we report that BIGH3 induces osteocyte apoptosis in both human RCCBM tissue specimens and in a preclinical mouse model. We also demonstrate that BIGH3 reduces Cx43 expression, blocking gap junction (GJ) function and osteocyte network communication. BIGH3-mediated GJ inhibition is blocked by the lysosomal inhibitor hydroxychloroquine (HCQ), but not osteoanabolic agents. Our results broaden the understanding of pathologic osteolysis in RCCBM and indicate that targeting the BIGH3 mechanism could be a combinational strategy for the treatment of RCCBM-induced bone disease that overcomes the limited efficacy of antiresorptives that target osteoclasts.
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    Changes in walking function and neural control following pelvic cancer surgery with reconstruction
    (Frontiers, 2024) Li, Geng; Ao, Di; Vega, Marleny M.; Zandiyeh, Payam; Chang, Shuo-Hsiu; Penny, Alexander N.; Lewis, Valerae O.; Fregly, Benjamin J.; Rice Computational Neuromechanics Laboratory
    Introduction: Surgical planning and custom prosthesis design for pelvic cancer patients are challenging due to the unique clinical characteristics of each patient and the significant amount of pelvic bone and hip musculature often removed. Limb-sparing internal hemipelvectomy surgery with custom prosthesis reconstruction has become a viable option for this patient population. However, little is known about how post-surgery walking function and neural control change from pre-surgery conditions. Methods: This case study combined comprehensive walking data (video motion capture, ground reaction, and electromyography) with personalized neuromusculoskeletal computer models to provide a thorough assessment of pre- to post-surgery changes in walking function (ground reactions, joint motions, and joint moments) and neural control (muscle synergies) for a single pelvic sarcoma patient who received internal hemipelvectomy surgery with custom prosthesis reconstruction. Pre- and post-surgery walking function and neural control were quantified using pre- and post-surgery neuromusculoskeletal models, respectively, whose pelvic anatomy, joint functional axes, muscle-tendon properties, and muscle synergy controls were personalized using the participant’s pre-and post-surgery walking and imaging data. For the post-surgery model, virtual surgery was performed to emulate the implemented surgical decisions, including removal of hip muscles and implantation of a custom prosthesis with total hip replacement. Results: The participant’s post-surgery walking function was marked by a slower self-selected walking speed coupled with several compensatory mechanisms necessitated by lost or impaired hip muscle function, while the participant’s post-surgery neural control demonstrated a dramatic change in coordination strategy (as evidenced by modified time-invariant synergy vectors) with little change in recruitment timing (as evidenced by conserved time-varying synergy activations). Furthermore, the participant’s post-surgery muscle activations were fitted accurately using his pre-surgery synergy activations but fitted poorly using his pre-surgery synergy vectors. Discussion: These results provide valuable information about which aspects of post-surgery walking function could potentially be improved through modifications to surgical decisions, custom prosthesis design, or rehabilitation protocol, as well as how computational simulations could be formulated to predict post-surgery walking function reliably given a patient’s pre-surgery walking data and the planned surgical decisions and custom prosthesis design.
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    Evaluation of finite element modeling methods for predicting compression screw failure in a custom pelvic implant
    (Frontiers Media S.A., 2024) Zhu, Yuhui; Babazadeh-Naseri, Ata; Brake, Matthew R. W.; Akin, John E.; Li, Geng; Lewis, Valerae O.; Fregly, Benjamin J.
    Introduction: Three-dimensional (3D)-printed custom pelvic implants have become a clinically viable option for patients undergoing pelvic cancer surgery with resection of the hip joint. However, increased clinical utilization has also necessitated improved implant durability, especially with regard to the compression screws used to secure the implant to remaining pelvic bone. This study evaluated six different finite element (FE) screw modeling methods for predicting compression screw pullout and fatigue failure in a custom pelvic implant secured to bone using nine compression screws. Methods: Three modeling methods (tied constraints (TIE), bolt load with constant force (BL-CF), and bolt load with constant length (BL-CL)) generated screw axial forces using functionality built into Abaqus FE software; while the remaining three modeling methods (isotropic pseudo-thermal field (ISO), orthotropic pseudo-thermal field (ORT), and equal-and-opposite force field (FOR)) generated screw axial forces using iterative physics-based relationships that can be implemented in any FE software. The ability of all six modeling methods to match specified screw pretension forces and predict screw pullout and fatigue failure was evaluated using an FE model of a custom pelvic implant with total hip replacement. The applied hip contact forces in the FE model were estimated at two locations in a gait cycle. For each of the nine screws in the custom implant FE model, likelihood of screw pullout failure was predicted using maximum screw axial force, while likelihood of screw fatigue failure was predicted using maximum von Mises stress. Results: The three iterative physics-based modeling methods and the non-iterative Abaqus BL-CL method produced nearly identical predictions for likelihood of screw pullout and fatigue failure, while the other two built-in Abaqus modeling methods yielded vastly different predictions. However, the Abaqus BL-CL method required the least computation time, largely because an iterative process was not needed to induce specified screw pretension forces. Of the three iterative methods, FOR required the fewest iterations and thus the least computation time. Discussion: These findings suggest that the BL-CL screw modeling method is the best option when Abaqus is used for predicting screw pullout and fatigue failure in custom pelvis prostheses, while the iterative physics-based FOR method is the best option if FE software other than Abaqus is used.