Explainable Deep Learning and Biomechanical Modeling for TMJ Disorder Morphological Risk Factors.

Clarifying multifactorial musculoskeletal disorder etiologies supports risk analysis and development of targeted prevention and treatment modalities. Deep learning enables comprehensive risk factor identification through systematic analysis of disease datasets but does not provide sufficient context for mechanistic understanding, limiting clinical applicability for etiological investigations. Conversely, multiscale biomechanical modeling can evaluate mechanistic etiology within the relevant biomechanical and physiological context. We propose a hybrid approach combining 3D explainable deep learning and multiscale biomechanical modeling; we applied this approach to investigate temporomandibular joint (TMJ) disorder etiology by systematically identifying risk factors and elucidating mechanistic relationships between risk factors and TMJ biomechanics and mechanobiology. Our 3D convolutional neural network recognized TMJ disorder patients through subject-specific morphological features in condylar, ramus, and chin. Driven by deep learning model outputs, biomechanical modeling revealed that small mandibular size and flat condylar shape were associated with increased TMJ disorder risk through increased joint force, decreased tissue nutrient availability and cell ATP production, and increased TMJ disc strain energy density. Combining explainable deep learning and multiscale biomechanical modeling addresses the "mechanism unknown" limitation undermining translational confidence in clinical applications of deep learning and increases methodological accessibility for smaller clinical datasets by providing the crucial biomechanical context.

Effects of Increased Retroversion Angle on Glenoid Baseplate Fixation in Reverse Total Shoulder Arthroplasty: A Finite Element Analysis.

BACKGROUND: Increased glenoid retroversion occurs in patients with severe arthritis but its effect on baseplate fixation of a reverse total shoulder arthroplasty (rTSA) is not clear. The purpose of this study is to determine the effects of increasing glenoid retroversion on baseplate fixation in rTSA using finite element analysis (FEA) modelling. METHODS: Five sets of computerized tomographic (CT) images of healthy normal shoulders were selected and segmented with Amira (Thermo Fisher Scientific) to obtain the solid geometries. Scapula FEA models with 5°, 10°, 15°, 20° and 25° retroversion angles were generated for each healthy scapula geometry and a rTSA glenoid baseplate was implanted on each model. Maximum stress at the anterior and posterior portions of the glenoid and the micromotion between the bone and baseplate were recorded. After simulation with normal scapular bone material properties (Young's modulus 4GPa and Poisson's ratio 0.3), another set of simulations was run on each subject with a 25° retroversion angle and poor bone quality (Young's modulus 500 MPa and Poisson's ratio 0.3) to study a worst-case scenario. Micromotions in each model were also recorded. All statistical analysis was done with SPSS. RESULTS: Simulation results of models generated from the same subject but with different retroversion angles showed a clear pattern: as retroversion angle increased, the stresses increased posteriorly and decreased anteriorly. Also, micromotion between the bone and the baseplate increased with the increase of retroversion angle. With analysis of variance (ANOVA), we found that all three values change significantly as the retroversion angle increases (p < 0.001). The simulation results also showed that micromotion was large in shoulders with small glenoid size and poor bone quality. However, even in the model with the worst-case scenario (smallest glenoid size, poorest bone quality and 25° retroversion angle), the maximum micromotion and the maximum stresses are still within the safe range. DISCUSSION: In all cases with both normal and poor bone quality, the stresses and micromotion stayed below the threshold to allow for bone ingrowth of the glenoid baseplate to occur. Based on these results, for glenoid baseplates with a central peg/post and 4 screws for fixation, rTSA baseplate retroversion does not need to be corrected to less than 10° to provide good initial fixation as has been recommended for a cemented glenoid component and can withstand the initial stresses and micromotion up to 25° of retroversion. LEVEL OF EVIDENCE: Basic Science Study; Computer Modeling.

Sexual dimorphisms in three-dimensional masticatory muscle attachment morphometry regulates temporomandibular joint mechanics.

Temporomandibular joint (TMJ) disorders disproportionally affect females, with female to male prevalence varying from 3:1 to 8:1. Sexual dimorphisms in masticatory muscle attachment morphometry and association with craniofacial size, critical for understanding sex-differences in TMJ function, have not been reported. The objective of this study was to determine sex-specific differences in three-dimensional (3D) TMJ muscle attachment morphometry and craniofacial sizes and their impact on TMJ mechanics. Human cadaveric TMJ muscle attachment morphometry and craniofacial anthropometry (10Males; 11Females) were determined by previously developed 3D digitization and imaging-based methods. Sex-differences in muscle attachment morphometry and craniofacial anthropometry, and their correlation were determined, respectively using multivariate general linear and linear regression statistical models. Subject-specific musculoskeletal models of the mandible were developed to determine effects of sexual dimorphisms in mandibular size and TMJ muscle attachment morphometry on joint loading during static biting. There were significant sex-differences in craniofacial size (p = 0.024) and TMJ muscle attachment morphometry (p < 0.001). TMJ muscle attachment morphometry was significantly correlated with craniofacial size. TMJ contact forces estimated from biomechanical models were significantly, 23% on average (p < 0.001), greater for females compared to those for males when generating the same bite forces. There were significant linear correlations between TMJ contact force and both 3D mandibular length (R2 = 0.48, p < 0.001) and muscle force moment arm ratio (R2 = 0.68, p < 0.001). Sexual dimorphisms in masticatory muscle morphology and craniofacial sizes play critical roles in subject-specific TMJ biomechanics. Sex-specific differences in the TMJ mechanical environment should be further investigated concerning mechanical fatigue of TMJ discs associated with TMJ disorders.

Biomechanical effect of selective osteotomy and corticotomy on orthodontic molar uprighting.

INTRODUCTION: Uprighting mesially tipped molars is often a necessary step before implant placement. However, the orthodontic treatment can be lengthy and discourage patients from choosing implant prostheses. Periodontally accelerated osteogenic orthodontics is reported to facilitate molar movements. This study aimed to evaluate the biomechanical effects of various corticotomy and osteotomy approaches on the uprighting of a mesially tipped mandibular second molar in a 3-dimensional finite element analysis model. METHODS: The initial tooth displacement and periodontal ligament (PDL) strain in 9 finite element analysis models with various corticotomy and osteotomy simulations were compared under 3 intended tooth movement scenarios: distal crown tipping, mesial root movement with restraints, and mesial root movement without restraints. RESULTS: Corticotomy or osteotomy approaches altered the tooth displacement and the PDL strain in all 3 intended molar uprighting scenarios. The 2 most extensive surgical approaches, the combined mesial and distal osteotomy with horizontal corticotomy and the circumferential corticotomy at root apex level, resulted in increased tooth movement but had a distinct impact on PDL strain. CONCLUSIONS: It was revealed that different combinations of corticotomy and osteotomy had a biomechanical impact on orthodontic molar uprighting movements.

Selective osteotomy-assisted molar uprighting and simultaneous ridge augmentation for implant site development.

Orthodontic treatment to upright an inclined molar adjacent to an edentulous space is often necessary before implant placement. The implant site may also require a ridge augmentation if the bony volume is not sufficient. The time required for both treatment steps can be lengthy and can discourage patients from accepting dental implants. This case report presents a novel interdisciplinary approach to implant site development. Selective osteotomy and simultaneous ridge augmentation were performed on the bilateral mesially inclined second molars before orthodontic uprighting. The severely inclined second molars were uprighted in 5 months, and the enhanced implant sites were ready for implant placement without complications. A finite element analysis revealed that the osteotomy partially affected the biomechanical responses of the dentoalveolar structures during molar uprighting.

Temporomandibular Joint Condyle-Disc Morphometric Sexual Dimorphisms Independent of Skull Scaling.

PURPOSE: Approximately 2 to 4% of the US population have been estimated to seek treatment for temporomandibular symptoms, predominately women. The study purpose was to determine whether sex-specific differences in temporomandibular morphometry result from scaling with sex differences in skull size and shape or intrinsic sex-specific differences. MATERIALS AND METHODS: A total of 22 (11 male [aged 74.5 ± 9.1 years]; 11 female [aged 73.6 ± 12.8 years]) human cadaveric heads with no history of temporomandibular disc derangement underwent cone beam computed tomography and high-resolution magnetic resonance imaging scanning to determine 3-dimensional cephalometric parameters and temporomandibular morphometric outcomes. Regression models between morphometric outcomes and cephalometric parameters were developed, and intrinsic sex-specific differences in temporomandibular morphometry normalized by cephalometric parameters were determined. Subject-specific finite element (FE) models of the extreme male and extreme female conditions were developed to predict variations in articular disc stress-strain under the same joint loading. RESULTS: In some cases, sex differences in temporomandibular morphometric parameters could be explained by linear scaling with skull size and shape; however, scaling alone could not fully account for some differences between sexes, indicating intrinsic sex-specific differences. The intrinsic sex-specific differences in temporomandibular morphometry included an increased condylar medial length and mediolateral disc lengths in men and a longer anteroposterior disc length in women. Considering the extreme male and female temporomandibular morphometry observed in the present study, subject-specific FE models resulted in sex differences, with the extreme male joint having a broadly distributed stress field and peak stress of 5.28 MPa. The extreme female joint had a concentrated stress field and peak stress of 7.37 MPa. CONCLUSIONS: Intrinsic sex-specific differences independent of scaling with donor skull size were identified in temporomandibular morphometry. Understanding intrinsic sex-specific morphometric differences is critical to determining the temporomandibular biomechanics given the effect of anatomy on joint contact mechanics and stress-strain distributions and requires further study as one potential factor for the increased predisposition of women to temporomandibular disc derangement.

Study of the Microstructure and Ring Element Segregation Zone of Spray Deposited SiCp/7055Al.

Composites of 7055 aluminum (Al) matrix reinforced with SiC particles were prepared using the spray deposition method. The volume fraction of the phase reinforced with SiC particles was 17%. The effect of the introduction of SiC particles on the deposited microstructure and properties of the composites was studied in order to facilitate the follow-up study. The structure and element enrichment zone of spray-deposited SiCp/7055 Al matrix composites were studied by Optical Microscope (OM), X-ray diffraction (XRD), Scanning Electronic Microscopy (SEM) and Transmission electron microscopy (TEM). The results show that the reinforcement phases of the SiC particles were uniformly distributed on the macro and micro levels, and a few SiC particles were segregated into annular closed regions. C and Si on the surface of SiC particles diffused to the Al matrix. The distribution of the two elements was gradient weakening with SiC particles as the center, and the enrichment zones of Si, Mg and Cu formed in the middle of the closed annular area of a few SiC particles. The enrichment zones were mainly composed of alpha-Al, SiC, Al2CuMg, Al2Cu and MgZn2. AlCu and AlMgCu phase precipitate on the surface of the SiC particles, beside the particle boundary, and had the characteristics of preferred nucleation. They tended to grow at the edges and corners of SiC particles. It was observed that the formation of nanoparticles in the alloy had a pinning effect on dislocations. The different cooling rates of the SiC particles and the Al matrix led to different aluminum liquid particle sizes, ranging from 20 to 150 µm. In the region surrounded by SiC particles, the phenomenon of large particles extruding small particles was widespread. Tearing edges and cracks continued to propagate around the SiC particles, increasing their propagation journey and delaying the fracture of the materials.

Three-dimensional temporomandibular joint muscle attachment morphometry and its impacts on musculoskeletal modeling.

In musculoskeletal models of the human temporomandibular joint (TMJ), muscles are typically represented by force vectors that connect approximate muscle origin and insertion centroids (centroid-to-centroid force vectors). This simplification assumes equivalent moment arms and muscle lengths for all fibers within a muscle even with complex geometry and may result in inaccurate estimations of muscle force and joint loading. The objectives of this study were to quantify the three-dimensional (3D) human TMJ muscle attachment morphometry and examine its impact on TMJ mechanics. 3D muscle attachment surfaces of temporalis, masseter, lateral pterygoid, and medial pterygoid muscles of human cadaveric heads were generated by co-registering measured attachment boundaries with underlying skull models created from cone-beam computerized tomography (CBCT) images. A bounding box technique was used to quantify 3D muscle attachment size, shape, location, and orientation. Musculoskeletal models of the mandible were then developed and validated to assess the impact of 3D muscle attachment morphometry on joint loading during jaw maximal open-close. The 3D morphometry revealed that muscle lengths and moment arms of temporalis and masseter muscles varied substantially among muscle fibers. The values calculated from the centroid-to-centroid model were significantly different from those calculated using the 'Distributed model', which considered crucial 3D muscle attachment morphometry. Consequently, joint loading was underestimated by more than 50% in the centroid-to-centroid model. Therefore, it is necessary to consider 3D muscle attachment morphometry, especially for muscles with broad attachments, in TMJ musculoskeletal models to precisely quantify the joint mechanical environment critical for understanding TMJ function and mechanobiology.

The role of uric acid in the pathogenesis of diabetic retinopathy based on Notch pathway.

OBJECTIVE: Uric acid has been proposed as an independent risk factor of diabetic retinopathy. Although Notch signaling was reported to be affected in the presence of high concentrations of uric acid or glucose, the underlying mechanisms of hyperuricemia through the Notch signaling pathway to promote the development of diabetic retinopathy remain unknown. METHODS: We incubated human retinal endothelial cells (HRECs) with high glucose, high uric acid and high glucose plus high glucose respectively and evaluated the apoptosis rate in different treated cells by Tunel staining. We induced diabetic model by intraperitoneally streptozotocin. Then healthy rats and diabetic rats were given with adenine and oteracil potassium by gavage. Using automatic biochemical analyzer to detect blood glucose, uric acid, urea nitrogen, creatinine levels, to verify the success of modeling. The expression and mRNA levels of ICAM-1, IL-6, MCP-1, TNF-a, receptors Notch 1, ligands Dll 1, Dll 4, Jagged 1, Jagged 2 were detected by RT-PCR and Western-Blot. Notch1 siRNA was used to interfere Notch signaling pathway, the expression and mRNA levels of ICAM-1, IL-6, MCP-1 and TNF-α was detected by RT-PCR and Western blot respectively. RESULTS: In vitro models, the apoptosis of HRECs cells in high uric acid plus high glucose group was the most significant. In vitro and vivo models, detection of inflammatory cytokines revealed that the expression of inflammatory cytokines increased most significantly in high uric acid plus high glucose group. Notch signaling pathway activity was also increased most significantly in high uric acid plus high glucose group. After Notch 1 siRNA transfection in high glucose and high glucose plus uric acid group, the activity of Notch signaling pathway was successfully down-regulated. We found that the apoptosis of HRECs was significantly decreased in cells transfected with Notch 1 siRNA compared to the blank vector group, and the expression of inflammatory cytokines in cells was also significantly decreased. CONCLUSION: Our study reported that high uric acid can promote the inflammation of the retina and increase the activity of Notch signaling pathway on the basis of high glucose. Hyperuricemia promotes the development of diabetic retinopathy by increasing the activity of Notch signaling pathway. Notch signaling pathway is a potential therapeutic target for diabetic retinopathy.

[In vitro effect of photoactivated hypericin on anti-Schistosoma japonicum adult male worms].

OBJECTIVE: To investigate the in vitro effect of photoactivated hypericin on anti-Schistosoma japonicum adult male worms. METHODS: Kunming mice were infected with 60-80 Schistosoma japonicum single-sex cercariae. At 6 weeks post-infection, the mice were sacrificed and adult male worms of S. japonicum were collected. The worms were incubated in DMEM medium containing different concentrations of hypericin (0.1, 0.2, 0.5, 1.0, 1.5, 2.0, and 2.5 micromol/L) in the presence or absence of light. In photoactivated hypericin groups, after 6 h of dark incubation the worms were exposed to LED light irradiation (590 nm) for 30, 60, 90, and 120 min, respectively, and then cultured overnight in darkness (16h). In the next morning, the parasites were washed, resuspended in drug-free medium, and incubated in the dark for 48 h. These worms were observed with stereomicroscopy and scanning electron microscopy (SEM). RESULTS: Photoactivated hypericin showed the ability to kill Schistosoma japonicum in vitro. The death rate was 20% in 0.1 micromol/L photoactivated hypericin group under 30 min irradiation, and 100% in 2 micromol/L under 90 min irradiation and 2.5 micromol/L under 60 min irradiation, respectively. In blank control group, DMSO control group, and hypericin groups without light irradiation, worms were alive. After 60 min irradiation, the worms in 1.0, 2.5, 5.0 micromol/L photoactivated hypericin groups showed spastic paralysis characterized by reduced body length, pronounced tight curl, body stiffness, and complete cessation of movement. Surface tegumental damages of adult worms in 2.0 micromol/L photoactivated hypericin group for 60 min irradiation were observed under SEM, such as vacuole formation, erosion and peeling of the tegument, collapse of the sensory papillae, and even the normal structure disappeared completely. Both death rate and morphological damage of the worms treated by photoactivated hypericin were positively correlated with hypericin dose and light irradiation time. CONCLUSION: Photoactivated hypericin has anti-Schistosoma japonicum adult male worms effect in vitro.

Heterogeneous interactome between Litopenaeus vannamei plasma proteins and Vibrio parahaemolyticus outer membrane proteins.

A great loss has been suffered by microbial infectious diseases under intensive shrimp farming in recent years. In this background, the understanding of shrimp innate immunity becomes an importantly scientific issue, but little is known about the heterogeneous protein-protein interaction between pathogenic cells and hosts, which is a key step for the invading microbes to infect internet organs through bloodstream. In the present study, bacterial outer membrane (OM) protein array and pull-down approaches are used to isolate both Vibrio parahaemolyticus OM proteins that bind to shrimp serum proteins and the shrimp serum proteins that interact with bacterial cells, respectively. Three interacting shrimp serum proteins, hemocyanin, ß-1,3-glucan binding protein and LV_HP_RA36F08r and thirty interacting OM proteins were determined. They form 63 heterogeneous protein-protein interactions. Nine out of the 30 OM proteins were randomly demonstrated to be up-regulated or down-regulated when bacterial cells were cultured with shrimp sera, indicating the biological significance of the network. The interesting findings uncover the complexity of struggle between host immunity and bacterial infection. Compared with our previous report on heterogeneous interactome between fish grill and bacterial OM proteins, the present study further extends the investigation from lower vertebrates to invertebrates and develops a bacterial OM protein array to identify the OM proteins bound with shrimp serum proteins, which elevates the frequencies of the bound OM proteins. Our results highlight the way to determine and understand the heterogeneous interaction between hosts and microbes.

Seasonal variation and correlation with environmental factors of photosynthesis and water use efficiency of Juglans regia and Ziziphus jujuba.

Both the photosynthetic light curves and CO(2) curves of Juglans regia L. and Ziziphus jujuba Mill. var. spinosa in three seasons were measured using a LI-6400 portable photosynthesis system. The maximal net photosynthetic rate (A(max)), apparent quantum efficiency(phi), maximal carboxylation rate (V(cmax)) and water use efficiency (WUE) of the two species were calculated based on the curves. The results showed that A(max) of J. regia reached its maximum at the late-season, while the highest values of A(max) of Z. jujuba occurred at the mid-season. The A(max) of J. regia was more affected by relative humidity (RH) of the atmosphere, while that of Z. jujuba was more affected by the air temperature. Light saturation point (LSP) and Light compensation point (LCP) of J. regia had a higher correlation with RH of the atmosphere, those of Z. jujuba, however, had a higher correlation with air temperature. V(cmax) of both J. regia and Z. jujuba had negative correlation with RH of the atmosphere. WUE of J. regia would decrease with the rise of the air temperature while that of Z. jujuba increased. Thus it could be seen that RH, temperature and soil moisture had main effect on photosynthesis and WUE of J. regia and Z. jujuba. Incorporating data on the physiological differences among tree species into forest carbon models will greatly improve our ability to predict alterations to the forest carbon budgets under various environmental scenarios such as global climate change, or with differing species composition.