Identifying Biomarkers and Therapeutic Targets by Multiomic Analysis for HNSCC: Precision Medicine and Healthcare Management.

Background: Head and neck squamous cell carcinoma (HNSCC) is one of the major types of cancer, with 900,000 cases and over 400,000 deaths annually. It constitutes 3-4% of all cancers in Europe and western countries. As early diagnosis is the key to treating the disease, reliable biomarkers play an important role in the precision medicine of HNSCC. Despite treatments, the survival rate of cancer patients remains unchanged, and this is mainly due to the failure to detect the disease early. Thus, the objective of this study is to identify reliable biomarkers for head and neck cancers for better healthcare management. Methods: In this study, all available, curated human genes were screened for their expression against HNSCC TCGA patient samples using genomic and proteomic data by various bioinformatic approaches and datamining. Docking studies were performed using AutoDock or online virtual screening tools for identifying potential ligands. Results: Sixty genes were short-listed, and most of them show a consistently higher expression in head and neck patient samples at both the mRNA and the protein level. Irrespective of human papillomavirus (HPV) status, all of them show a higher expression in cancer samples. The higher expression of 30 genes shows adverse effects on patient survival. Out of the 60 genes, 12 genes have crystal structures and druggable potential. We show that genes such as GTF2H4, HAUS7, MSN, and MNDA could be targets of Pembrolizumab and Nivolumab, which are approved monoclonal antibodies for HNSCC. Conclusion: Sixty genes are identified as potential biomarkers for head and neck cancers based on their consistent and statistically significantly higher expression in patient samples. Four proteins have been identified as potential drug targets based on their crystal structure. However, the utility of these candidate genes has to be further tested using patient samples.

Investigation on three-dimensional printed prosthetics leg sockets coated with different reinforcement materials: analysis on mechanical strength and microstructural.

Previous research has primarily focused on pre-processing parameters such as design, material selection, and printing techniques to improve the strength of 3D-printed prosthetic leg sockets. However, these methods fail to address the major challenges that arise post-printing, namely failures at the distal end of the socket and susceptibility to shear failure. Addressing this gap, the study aims to enhance the mechanical properties of 3D-printed prosthetic leg sockets through post-processing techniques. Fifteen PLA + prosthetic leg sockets are fabricated and reinforced with four materials: carbon fiber, carbon-Kevlar fiber, fiberglass, and cement. Mechanical and microstructural properties of the sockets are evaluated through axial compression testing and scanning electron microscopy (SEM). Results highlight superior attributes of cement-reinforced sockets, exhibiting significantly higher yield strength (up to 89.57% more than counterparts) and higher Young's modulus (up to 76.15% greater). SEM reveals correlations between microstructural properties and socket strength. These findings deepen the comprehension of 3D-printed prosthetic leg socket post-processing, presenting optimization prospects. Future research can focus on refining fabrication techniques, exploring alternative reinforcement materials, and investigating the long-term durability and functionality of post-processed 3D-printed prosthetic leg sockets.

Unilateral external fixator and its biomechanical effects in treating different types of femoral fracture: A finite element study with experimental validated model.

Previous works had successfully demonstrated the clinical effectiveness of unilateral external fixator in treating various types of fracture, ranging from the simple type, such as oblique and transverse fractures, to complex fractures. However, literature that investigated its biomechanical analyses to further justify its efficacy is limited. Therefore, this paper aimed to analyse the stability of unilateral external fixator for treating different types of fracture, including the simple oblique, AO32C3 comminuted, and 20 mm gap transverse fracture. These fractures were reconstructed at the distal diaphysis of the femoral bone and computationally analysed through the finite element method under the stance phase condition. Findings showed a decrease in the fixation stiffness in large gap fracture (645.2 Nmm-1 for oblique and comminuted, while 23.4 Nmm-1 for the gap fracture), which resulted in higher displacement, IFM and stress distribution at the pin bone interface. These unfavourable conditions could consequently increase the risk of delayed union, pin loosening and infection, as well as implant failure. Nevertheless, the stress observed on the fracture surfaces was relatively low and in controlled amount, indicating that bone unity is still allowable in all models. Briefly, the unilateral fixation may provide desirable results in smaller fracture gap, but its usage in larger gap fracture might be alarming. These findings could serve as a guide and insight for surgeons and researchers, especially on the biomechanical stability of fixation in different fracture types and how will it affect bone unity.

Performance of textured dual mobility total hip prosthesis with a concave dimple during Muslim prayer movements.

The single mobility bearing as a previous bearing design of total hip prosthesis has severe mobility constraints that can result in dislocation during Muslim (people who follow the Islam as religion) prayer movements, specifically shalat that requires intense movement. There are five intense movements (i.e., bowing, prostration, sitting, transition from standing to prostration, and final sitting) during Muslim prayer that may generate an impingement problem for patients with total hip prosthesis. In this work, textured dual mobility total hip prosthesis with two textured cases (i.e., textured femoral head and textured inner liner) are presented and their performances are numerically evaluated against untextured surface model during Muslim prayer movement. The concave dimple design is chosen for surface texturing, while for simulating femoral head materials, SS 316L and CoCrMo is choosen. To represent the real condition, three-dimensional computational fluid dynamics (CFD) coupled with two-way fluid-structure interaction (FSI) methods are employed to analyze elastohydrodynamic lubrication problem with non-Newtonian synovial fluid model. The main aim of the present study is to investigate the tribological performance on dual mobility total hip prosthesis with applied textured surface with concave dimple in femoral head and inner liner surface under Muslim prayer movements. It is found that applying surface texturing has a beneficial effect on the lubrication performance for some intense movements. The textured femoral head model performs better than textured inner liner model and untextured model (both femoral head and inner liner). The numerical results also indicate superior performance of CoCrMo femoral head compared to SS 316L femoral head. These findings can be used as a reference for biomedical engineers and orthopedic surgeons in designing and choosing suitable total hip prosthesis for Muslims makes they can carry out Muslim prayer movements like humans in general who have normal hip joints.

Running-in behavior of dual-mobility cup during the gait cycle: A finite element analysis.

The running-in process is considered an essential aspect of the comprehensive wear process. The phenomenon of running-in occurs during the initial stages of wear in the prosthetic hip joint. Within the field of tribology, the running-in phenomenon of the hip joint pertains to the mechanism by which the contact surfaces of the artificial hip joint components are adjusted and a suitable lubricating film is formed. During the process of hip joint running-in, there is an interaction between the metal surface of the ball and the joint cup, which results in adjustments being made until a steady state is achieved. The achievement of desirable wear existence and reliable performance of artificial hip joint components are reliant upon the tribological running-in of the hip joint. Despite the establishment of current modeling approaches, there remains a significant lack of understanding concerning running-in wear, particularly the metal-on-polyethylene (MoP) articulations in dual-mobility cups (DMC). An essential aspect to consider is the running-in phase of the dual mobility component. The present study employed finite element analysis to investigate the running-in behavior of dual mobility cups, wherein femoral head components were matched with polyethylene liners of varying thicknesses. The analysis of the running-in phase was conducted during the normal gait cycle. The results of this investigation may be utilized to design a dual-mobility prosthetic hip joint that exhibits minimal running-in wear.

Electric Discharge Machining of Ti6Al4V ELI in Biomedical Industry: Parametric Analysis of Surface Functionalization and Tribological Characterization.

The superior engineering properties and excellent biocompatibility of titanium alloy (Ti6Al4V) stimulate applications in biomedical industries. Electric discharge machining, a widely used process in advanced applications, is an attractive option that simultaneously offers machining and surface modification. In this study, a comprehensive list of roughening levels of process variables such as pulse current, pulse ON time, pulse OFF time, and polarity, along with four tool electrodes of graphite, copper, brass, and aluminum are evaluated (against two experimentation phases) using a SiC powder-mixed dielectric. The process is modeled using the adaptive neural fuzzy inference system (ANFIS) to produce surfaces with relatively low roughness. A thorough parametric, microscopical, and tribological analysis campaign is established to explore the physical science of the process. For the case of the surface generated through aluminum, a minimum friction force of ~25 N is observed compared with the other surfaces. The analysis of variance shows that the electrode material (32.65%) is found to be significant for the material removal rate, and the pulse ON time (32.15%) is found to be significant for arithmetic roughness. The increase in pulse current to 14 A shows that the roughness increased to ~4.6 µm with a 33% rise using the aluminum electrode. The increase in pulse ON time from 50 µs to 125 µs using the graphite tool resulted in a rise in roughness from ~4.5 µm to ~5.3 µm, showing a 17% rise.

Biomechanical Effects of the Porous Structure of Gyroid and Voronoi Hip Implants: A Finite Element Analysis Using an Experimentally Validated Model.

Total hip arthroplasty (THA) is most likely one of the most successful surgical procedures in medicine. It is estimated that three in four patients live beyond the first post-operative year, so appropriate surgery is needed to alleviate an otherwise long-standing suboptimal functional level. However, research has shown that during a complete THA procedure, a solid hip implant inserted in the femur can damage the main arterial supply of the cortex and damage the medullary space, leading to cortical bone resorption. Therefore, this study aimed to design a porous hip implant with a focus on providing more space for better osteointegration, improving the medullary revascularisation and blood circulation of patients. Based on a review of the literature, a lightweight implant design was developed by applying topology optimisation and changing the materials of the implant. Gyroid and Voronoi lattice structures and a solid hip implant (as a control) were designed. In total, three designs of hip implants were constructed by using SolidWorks and nTopology software version 2.31. Point loads were applied at the x, y and z-axis to imitate the stance phase condition. The forces represented were x = 320 N, y = -170 N, and z = -2850 N. The materials that were used in this study were titanium alloys. All of the designs were then simulated by using Marc Mentat software version 2020 (MSC Software Corporation, Munich, Germany) via a finite element method. Analysis of the study on topology optimisation demonstrated that the Voronoi lattice structure yielded the lowest von Mises stress and displacement values, at 313.96 MPa and 1.50 mm, respectively, with titanium alloys as the materials. The results also indicate that porous hip implants have the potential to be implemented for hip implant replacement, whereby the mechanical integrity is still preserved. This result will not only help orthopaedic surgeons to justify the design choices, but could also provide new insights for future studies in biomechanics.

Analysis of contact pressure in a 3D model of dual-mobility hip joint prosthesis under a gait cycle.

Hip joint prostheses are used to replace hip joint function in the human body. The latest dual-mobility hip joint prosthesis has an additional component of an outer liner that acts as a cover for the liner component. Research on the contact pressure generated on the latest model of a dual-mobility hip joint prosthesis under a gait cycle has never been done before. The model is made of ultrahigh molecular weight polyethylene (UHMWPE) on the inner liner and 316L stainless steel (SS 316L) on the outer liner and acetabular cup. Simulation modeling using the finite element method is considered static loading with an implicit solver for studying the geometric parameter design of dual-mobility hip joint prostheses. In this study, simulation modeling was carried out by applying varying inclination angles of 30°, 40°, 45°, 50°, 60°, and 70° to the acetabular cup component. Three-dimensional loads were placed on femoral head reference points with variations of femoral head diameter used at 22 mm, 28 mm, and 32 mm. The results in the inner surface of the inner liner, the outer surface of the outer liner, and the inner surface of the acetabular cup showed that the variations in inclination angle do not have a major effect on the maximum contact pressure value on the liner component, where the acetabular cup with an inclination angle of 45° can reduce contact pressure more than the other studied inclination angle variations. In addition, it was found that the 22 mm diameter of the femoral head increases the contact pressure. The use of a larger diameter femoral head with an acetabular cup configuration at a 45° inclination can minimize the risk of implant failure due to wear.

Polycrystalline Diamond as a Potential Material for the Hard-on-Hard Bearing of Total Hip Prosthesis: Von Mises Stress Analysis.

Due to polymeric wear debris causing osteolysis from polymer, metal ions causing metallosis from metal, and brittle characteristic causing fracture failure from ceramic in the application on bearing of total hip prosthesis requires the availability of new material options as a solution to these problems. Polycrystalline diamond (PCD) has the potential to become the selected material for hard-on-hard bearing in view of its advantages in terms of mechanical properties and biocompatibility. The present study contributes to confirming the potential of PCD to replace metals and ceramics for hard-on-hard bearing through von Mises stress investigations. A computational simulation using a 2D axisymmetric finite element model of hard-on-hard bearing under gait loading has been performed. The percentage of maximum von Mises stress to respective yield strength from PCD-on-PCD is the lowest at 2.47%, with CoCrMo (cobalt chromium molybdenum)-on-CoCrMo at 10.79%, and Al2O3 (aluminium oxide)-on-Al2O3 at 13.49%. This confirms that the use of PCD as a hard-on-hard bearing material is the safest option compared to the investigated metal and ceramic hard-on-hard bearings from the mechanical perspective.

The Effect of Tortuosity on Permeability of Porous Scaffold.

In designing porous scaffolds, permeability is essential to consider as a function of cell migration and bone tissue regeneration. Good permeability has been achieved by mimicking the complexity of natural cancellous bone. In this study, a porous scaffold was developed according to the morphological indices of cancellous bone (porosity, specific surface area, thickness, and tortuosity). The computational fluid dynamics method analyzes the fluid flow through the scaffold. The permeability values of natural cancellous bone and three types of scaffolds (cubic, octahedron pillar, and Schoen's gyroid) were compared. The results showed that the permeability of the Negative Schwarz Primitive (NSP) scaffold model was similar to that of natural cancellous bone, which was in the range of 2.0 × 10-11 m2 to 4.0 × 10-10 m2. In addition, it was observed that the tortuosity parameter significantly affected the scaffold's permeability and shear stress values. The tortuosity value of the NSP scaffold was in the range of 1.5-2.8. Therefore, tortuosity can be manipulated by changing the curvature of the surface scaffold radius to obtain a superior bone tissue engineering construction supporting cell migration and tissue regeneration. This parameter should be considered when making new scaffolds, such as our NSP. Such efforts will produce a scaffold architecturally and functionally close to the natural cancellous bone, as demonstrated in this study.

Adopted walking condition for computational simulation approach on bearing of hip joint prosthesis: review over the past 30 years.

Bearing on artificial hip joint experiences friction, wear, and surface damage that impact on overall performance and leading to failure at a particular time due to continuous contact that endangers the user. Assessing bearing hip joint using clinical study, experimental testing, and mathematical formula approach is challenging because there are some obstacles from each approach. Computational simulation is an effective alternative approach that is affordable, relatively fast, and more accessible than other approaches in examining various complex conditions requiring extensive resources and several different parameters. In particular, different gait cycles affect the sliding distance and distribution of gait loading acting on the joints. Appropriate selection and addition of gait cycles in computation modelling are crucial for accurate and reliable prediction and analysis of bearing performance such as wear a failure of implants. However, a wide spread of gait cycles and loading data are being considered and studied by researchers as reported in literature. The current article describes a comprehensive literature review adopted walking condition that has been carried out to study bearing using computational simulation approach over the past 30 years. Many knowledge gaps related to adoption procedures, simplification, and future research have been identified to obtain bearing analysis results with more realistic computational simulation approach according to physiological human hip joints.

Computational Contact Pressure Prediction of CoCrMo, SS 316L and Ti6Al4V Femoral Head against UHMWPE Acetabular Cup under Gait Cycle.

Due to various concerns about the use of metal-on-metal that is detrimental to users, the use of metal as acetabular cup material was later changed to ultra high molecular weight polyethylene (UHMWPE). However, the wear on UHMWPE releases polyethylene wear particles, which can trigger a negative body response and contribute to osteolysis. For reducing the wear of polyethylene, one of the efforts is to investigate the selection of metal materials. Cobalt chromium molybdenum (CoCrMo), stainless steel 316L (SS 316L), and titanium alloy (Ti6Al4V) are the frequently employed materials. The computational evaluation of contact pressure was carried out using a two-dimensional axisymmetric model for UHMWPE acetabular cup paired with metal femoral head under gait cycle in this study. The results show Ti6Al4V-on-UHMWPE is able to reduce cumulative contact pressure compared to SS 316L-on-UHMWPE and CoCrMo-on-UHMWPE. Compared to Ti6Al4V-on-UHMWPE at peak loading, the difference in cumulative contact pressure to respective maximum contact pressure is 9.740% for SS 316L-on-UHMWPE and 11.038% for CoCrMo-on-UHMWPE.

Physiological Effect of Deep Pressure in Reducing Anxiety of Children with ASD during Traveling: A Public Transportation Setting.

Traveling with children with autism can be very challenging for parents due to their reactions to sensory stimuli resulting in behavioral problems, which lead to self-injury and danger for themselves and others. Deep pressure was reported to have a calming effect on people with autism. This study was designed to investigate the physiological effect of deep pressure, which is an autism hug machine portable seat (AHMPS) in children with autism spectrum disorders (ASD) in public transportation settings. The study was conducted with 20 children with ASD (16 boys and 4 girls) at the Semarang Public Special School with an age ranging from 4 to 13 years (mean 10.9 ± 2.26 years), who were randomly assigned into two groups. The experiment consisted of group I who used the AHMPS inflatable wraps model and group II who used the AHMPS manual pull model. Heart rate (HR) and skin conductance (SC) were analyzed to measure the physiological calming effect using pulse oximeter oximetry and a galvanic skin response (GSR) sensor. Heart rate was significantly decreased during the treatment compared to the baseline (pre-test) session in group I (inflating wrap model) with p = 0.019, while no change of heart rate variability (HRV) was found in group II (manual pull model) with p = 0.111. There was no remaining effect of deep pressure using the HRV indicator after the treatment in both groups (group I with p = 0.159 and group II with p = 0.566). GSR captured the significant decrease in skin conductance during the treatment with p < 0.0001 in group I, but no significant decrease was recorded in group II with p = 0.062. A skin conductance indicator captured the remaining effect of deep pressure (after the treatment); it was better in group I (p = 0.003) than in group II (p = 0.773). In conclusion, the deep pressure of the AHMPS inflating wrap decreases physiological arousal in children with ASD during traveling.

Effect of Short-Term Deep-Pressure Portable Seat on Behavioral and Biological Stress in Children with Autism Spectrum Disorders: A Pilot Study.

Children with autism spectrum disorder (ASD) have challenging behaviors, which are associated with difficulties in parenting. Deep pressure is a therapeutic modality in occupational therapy, and it was reported to produce a calming effect. This study aimed to determine whether the short-term use of an autism hug machine portable seat (AHMPS) improves behavioral and neurobiological stress in children with ASD, and to determine whether AHMPS with an inflatable wrap or manual pull is more effective. This study enrolled children with ASD who were administered with the inflatable wrap (group I) and manual pull (group II) for 20 min twice a week for 3 weeks. Conners' Parent Rating Scale-48 (CPRS-48) was used to rate behavioral improvements, and galvanic skin response (GSR) was used to measure sympathetic stress response. A total of 20 children with ASD (14 boys and 6 girls; aged 7-13 years) were included. CPRS-48 presented conduct problems: behavior was significantly decreased in the inflatable group (p = 0.007) compared to the manual pull group. The GSR captured a significant reduction in sympathetic response (p = 0.01) only in group I. Neurobiological stress was reduced in children who were wearing the AHMPS inflatable wrap; therefore, AHMPS inflatable wrap is an effective method to reduce emotional arousal.

Tresca Stress Simulation of Metal-on-Metal Total Hip Arthroplasty during Normal Walking Activity.

The selection of biomaterials for bearing in total hip arthroplasty is very important to avoid various risks of primary postoperative failure for patients. The current investigation attempts to analyze the Tresca stress of metal-on-metal bearings with three different materials, namely, cobalt chromium molybdenum (CoCrMo), stainless steel 316L (SS 316L), and titanium alloy (Ti6Al4V). We used computational simulations using a 2D axisymmetric finite element model to predict Tresca stresses under physiological conditions of the human hip joint during normal walking. The simulation results show that Ti6Al4V-on-Ti6Al4V has the best performance to reduce Tresca stress by 45.76% and 39.15%, respectively, compared to CoCrMo-on-CoCrMo and SS 316L-on-SS 316L.

The Effect of Bottom Profile Dimples on the Femoral Head on Wear in Metal-on-Metal Total Hip Arthroplasty.

Wear and wear-induced debris is a significant factor in causing failure in implants. Reducing contact pressure by using a textured surface between the femoral head and acetabular cup is crucial to improving the implant's life. This study presented the effect of surface texturing as dimples on the wear evolution of total hip arthroplasty. It was implemented by developing finite element analysis from the prediction model without dimples and with bottom profile dimples of flat, drill, and ball types. Simulations were carried out by performing 3D physiological loading of the hip joint under normal walking conditions. A geometry update was initiated based on the patient's daily routine activities. Our results showed that the addition of dimples reduced contact pressure and wear. The bottom profile dimples of the ball type had the best ability to reduce wear relative to the other types, reducing cumulative linear wear by 24.3% and cumulative volumetric wear by 31% compared to no dimples. The findings demonstrated that surface texturing with appropriate dimple bottom geometry on a bearing surface is able to extend the lifetime of hip implants.