Computational Modeling Studies Research Articles

Impacts of Hip Osteoarthritis on Spinal Sagittal Alignment and Surgical Outcomes in Patients with Adult Spinal Deformity: Evidence from Meta-analysis and Two-sample Mendelian Randomization.

A considerable proportion of patients with adult spinal deformity (ASD) have concomitant hip osteoarthritis (HOA). However, no studies have systematically summarized the impacts of HOA on ASD patients, either radiologically or clinically. To compare the spinal sagittal alignment parameters pre- and postoperatively, along with patient-reported outcomes and complications following surgery in ASD patients with or without severe HOA (Kellgren-Lawrence grade 3-4). Systematic review and meta-analysis. We searched the PubMed, Embase, Scopus, Cochrane Library, Google scholar, ClinicalTrials.gov, ProQuest Dissertations and These, and Open Grey for articles with a publication cutoff of July 28, 2024. The inclusion criteria were: (1) comparative studies of ASD patients with and without severe HOA, (2) outcomes reported as spinal radiographic outcomes (such as pelvic tilt (PT), sacrofemoral angle (SFA), knee angle (KA), or sagittal vertical axis (SVA), etc.), patient-reported outcomes (such as SRS-22r, ODI, VR-12 PCS, etc.), and complications (such as proximal junctional kyphosis, pseudarthrosis, reoperation, etc.), and (3) randomized controlled trials and observational studies published in English. The exclusion criteria were (1) reviews, case series, case reports, letters, and conference reports, (2) in vitro biomechanical studies and computational modelling studies, (3) no report on study outcomes, and (4) studies with < 10 patients per group. Additionally, a two-sample mendelian randomization (MR) study using genetic variants associated with HOA as instrumental variables was conducted. Four observational studies with a total of 891 ASD patients (672 minimal HOA, 219 severe HOA) were included. Based on our meta-analysis, ASD patients with severe HOA exhibited significantly lower PT (95% CI: 0.09-0.57) and SFA (5% CI: 0.31-0.68), along with higher KA (95% CI: -0.52- -0.19), SVA (95% CI: -0.75- -0.41), global sagittal angle (95% CI: -0.71- -0.16), and posterior pelvic shift (95% CI: -0.93- -0.25) than those with minimal HOA. Furthermore, concomitant severe HOA was associated with higher postoperative SVA, worse VR-12 PCS, and increased risk of pseudarthrosis and reoperation based on a review of the literature. The MR study indicated a causal association between HOA and intervertebral disc degeneration related traits, including early lumbar prolapse (95% CI: 1.08-1.46), intervertebral disc disorders (95% CI: 1.07-1.32), and low back pain (95% CI: 1.02-1.17). Moreover, HOA was proven to relate to sarcopenia related traits, including usual walking pace (95% CI: -0.04- -0.02) and hand grip strength (95% CI: -0.06- -0.01). Radiologically, concomitant HOA in patients with ASD appears to be associated with limited pelvic compensatory capacity and worse global spinal sagittal alignment. Clinically, ASD patients with HOA may experience worse patient-reported outcomes and higher incidence of mechanical complications. Moreover, the presence of HOA promotes the progression of IVDD and sarcopenia, which could partially account for its impacts.

Design, synthesis, anti-inflammatory evaluation, and molecular docking studies of novel quinazoline-4(3H)-one-2-carbothioamide derivatives.

In this paper, a series of novel quinazoline-4(3H)-one-2-carbothioamide derivatives (8a-p) were designed and synthesized via the Wilgerodt-Kindler reaction between 2-methylquinazoline-4-one 10 and amines using S8/DMSO as the oxidizing system. Their characteristics were confirmed by IR, NMR, HRMS spectra, and their melting point. These novel derivatives (8a-p) were evaluated for their anti-inflammatory activity by inhibiting NO production in lipopolysaccharide (LPS)-activated RAW 264.7 macrophage cells. Compounds 8d (IC50 = 2.99 μM), 8g (IC50 = 3.27 μM), and 8k (IC50 = 1.12 μM) exhibited potent inhibition of NO production compared to the standard drug dexamethasone (IC50 = 14.20 μM). Compound 8a (IC50 = 13.44 μM) exhibited NO inhibition comparable to dexamethasone. Structure-activity relationship (SAR) studies indicated that the presence of both the thioamide functional group (NH-C[double bond, length as m-dash]S) directly attached to the phenyl ring containing halogen substituents (4-Cl, 8d), (4-Br, 8g) and (4-CF3, 8k), is responsible for the potent anti-inflammatory activity of these novel quinazolinone derivatives. Computational modeling studies revealed that compounds 8d, 8g, and 8k are potent inhibitors of TLR4 signaling through the formation of hydrophobic interactions and are stabilized by hydrogen bonds. Replacing the thioamide (8k) with an amide (8q) resulted in an 83-fold decrease in NO inhibitory potency. This highlights the important role of H-bonding involving the thioamide group. The structural shape difference results in favorable interactions of quinazolinones containing thioamide linkers compared to amide linkers to the target receptor. Furthermore, the ADMET profiles and physicochemical properties of these three lead compounds were predicted to meet the criteria for drug-like properties. Therefore, these compounds may be potential candidates for the treatment of many inflammatory diseases associated with immune disorders.

Influence of hip morphology on gluteal muscle biomechanics: a computational modeling study

BackgroundHip morphology variations, particularly in femoral neck shaft angle (NSA) and iliac wing width (IWW), have been associated with gluteal tendinopathy. However, the biomechanical implications of these morphological differences on gluteal muscle function are not well understood. This study investigates how NSA and IWW influence gluteal muscle forces, moment arms, and estimated tendon loads during walking, aiming to provide insights into the potential biomechanical pathways that may contribute to altered lateral hip loading patterns.MethodsWe modified a musculoskeletal model to reflect varying NSAs (108°, 123° and 143°) and IWWs (185, 265 and 345 mm), simulating nine gait cycles to assess the impact on the moment arms and loading of the gluteus medius (GMed) and minimus (Gmin) muscles.ResultsModels revealed that a high NSA with a narrow IWW (NSA143°/IWW185 mm) resulted in the shortest moment arms (GMed, 26 mm; Gmin, 29 mm) and highest peak muscle forces (GMed, 1240 N; GMin, 242 N), suggesting a biomechanical predisposition to gluteal tendinopathy. Conversely, a low NSA with a wide IWW (NSA108°/IWW345 mm) produced the longest moment arms (GMed, 47 mm; GMin, 45 mm) and lowest peak muscle forces (GMed, 742 N; GMin, 145 N). A 4° decrease in NSA reduced tensile load by 37 N (4.0%, p < 0.001) for GMed and 4 N (2.7%, p = 0.025) for GMin, with a minor increase in GMin compressive load by 2 N (1.8%, p = 0.048). A 10 mm decrease in IWW increased tensile and compressive loads by 12 N (1.3%, p < 0.001) and 20 N (20%, p < 0.001) for GMed, and by 3 N (2%, p < 0.007) and 3 N (2.7%, p < 0.007) for GMin.ConclusionsOur biomechanical modeling suggests patients with narrow iliac width may be predisposed to gluteal tendinopathy through increased tendon loading. The protective mechanical effect of decreased neck shaft angle suggests its clinical association with tendinopathy likely involves other factors, such as IT band compression which was not accounted for in this study. For clinical assessment, iliac width measurement may help identify at-risk patients and guide preventive interventions, while neck shaft angle should be evaluated within a broader anatomical context.

Inclusion Complex of Water-soluble Arbutin with β-Cyclodextrin: Computer Modeling and Experimental Studies

Inclusion Complex of Water-soluble Arbutin with β-Cyclodextrin: Computer Modeling and Experimental Studies

Design, Structure-Activity Relationships, and Computational Modeling Studies of a Series of α-Helix Biased, Ultra-Short Glucagon-like Peptide-1 Receptor Agonists.

A systematic structure-activity and computational modeling analysis of a series of glucagon-like peptide-1 receptor (GLP-1R) agonists based upon an ultra-short GLP-1 peptide, H-His-Aib-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Bip-Bip-NH2, was conducted. This highly potent 11-mer peptide led to a deeper understanding of the α-helical bias of strategic α-methylation within the linear parent template as well as optimization of GLP-1R agonist potency by 1000-fold. These data were correlated with previously reported co-structures of both full-length GLP-1 analogs and progenitor N-terminal GLP-1 fragment analogs related to such ultra-short GLP-1R agonist peptides. Furthermore, the development of a quantitative structure-activity relationship (QSAR) model to analyze these findings is described in this study.

Optic nerve-mediated modulation of temporally interfering electric fields for potential targeted retinal disease therapy: a computational modeling study

IntroductionTraditional extraocular electrical stimulation typically produces diffuse electric fields across the retina, limiting the precision of targeted therapy. Temporally interfering (TI) electrical stimulation, an emerging approach, can generate convergent electric fields, providing advantages for targeted treatment of various eye conditions.ObjectiveUnderstanding how detailed structures of the retina, especially the optic nerve, affects electric fields can enhance the application of TI approach in retinal neurodegenerative and vascular diseases, an essential aspect that has been frequently neglected in previous researches.MethodsWe developed an anatomically accurate multi-layer human eye model, incorporating the optic nerve segment and setting it apart from current research endeavors. Based on this model, we conducted in silico investigations to predict the influence of the optic nerve on spatial characteristics of the temporally interfering electric field (TIEF) generated by diverse electrode configurations.ResultsOptic nerve directly influenced spatial distributions and modulation rules of TIEFs. It caused convergent areas to shift nasally or temporally in relation to return electrode positions, and further increased the axial anisotropy within the convergent TIEF. Furthermore, alterations in electrode positions and adjustments to current ratios among channels induced diverse spatial patterns of TIEFs within the macular region, the area surrounding the optic nerve, as well as peripheral retina.ConclusionOur findings suggested that presence of the optic nerve necessitated the utilization of different modulating paradigms when employing TI strategy for targeted treatment of various retinal lesions. And also provided theoretical references for developing a novel retinal electrical stimulation therapeutic device based on TI technology.

Nasal absorption of oxycodone predicted using a novel computational fluid dynamics-physiologically based pharmacokinetic model.

Oxycodone hydrochloride (HCl) extended release (ER) tablet is an abuse-deterrent formulation that uses a physical barrier to make it more difficult to crush tablets prior to abuse via various routes. A previously conducted in vivo pharmacokinetics (PK) study showed that particle size exhibited significant effects on PK. Here, a computational modeling study using a novel combined computational fluid dynamics and physiologically based PK model was applied to better understand the mechanisms that produce differences in PK according to particle size and formulation type for nasally insufflated oxycodone HCl immediate release (IR) and ER tablets. Dissolution data were collected using a United States Pharmacopeia (USP) Apparatus 4 to support model parameterization. The in vitro dissolution data showed that the number of powder layers in the bead-based system impacted the observed dissolution pattern for the finely milled (106-500 μm) ER formulations, but not the finely milled IR (106-500 μm) or coarsely milled ER (500-1000 μm) formulations. The model was validated via comparison of PK predictions with available in vivo PK data for finely milled (106-500 μm) IR and ER formulations in the 30 mg strength, a coarsely milled (500-1000 μm) ER formulation in the 30 mg strength, and a finely milled ER formulation in the 80 mg strength. Model predictions showed relative differences no greater than 3.3 % for maximum plasma concentration (Cmax) and 14.9 % for area under the plasma concentration time curve from time zero to the last time point, as well as absolute differences no greater than 0.8 h for time to Cmax. The residence time in the nasal cavity was predicted to be 1 h for finely milled ER formulations as compared with approximately 20 min for the finely milled IR and coarsely milled ER formulations. When differences in dissolution input data were considered, there were noticeable changes in PK predictions observed for the finely milled ER formulations, according to the different number of powder layers in the USP Apparatus 4. Overall, the results of this study suggest that biopredictive in vitro characterization of abuse deterrence via the nasal route for an oxycodone HCl ER tablet drug product may include methods to characterize dissolution and impacts of formulation on residence time in the nasal cavity.

Fisetin as a Blueprint for Senotherapeutic Agents - Elucidating Geroprotective and Senolytic Properties with Molecular Modeling.

Targeting senescent cells and the factors that accelerate this pathological state has recently emerged as a novel field in medicinal chemistry. As attention shifts to synthetic substances, studies on natural agents are often overlooked. In this paper, we present a detailed computational modeling study that encompasses quantum mechanics and molecular dynamics to elucidate the senotherapeutic activity of fisetin. The mitochondrial environment, serving as a proxy for senescence, received special attention. Throughout the study, fisetin's outstanding geroprotective properties-exhibiting significant potential against•OOH, O2•-, and•OH radicals, surpassing those of Trolox or ascorbate-were identified. Furthermore, fisetin demonstrated a high capacity to restore oxidatively damaged biomolecules to their pristine forms, thereby renewing the functionality of proteins and amino acids. The senolytic properties were examined in terms of Bcl-2 and Bcl-xL inhibition. The results indicated that fisetin not only binds effectively to these proteins but also, with appropriate modifications, may exhibit specific selectivity toward either target. This study highlights fisetin's remarkable activity in these areas and provides a molecular description of the underlying processes, paving the way for future research.

Halloysite Clay Nanotubes for Catalytic Conversion of Biomass: Synergy between Computational Modeling and Experimental Studies

Halloysite Clay Nanotubes for Catalytic Conversion of Biomass: Synergy between Computational Modeling and Experimental Studies

Xylose Acetals - a New Class of Sustainable Solvents and Their Application in Enzymatic Polycondensation.

The use of organic solvents in academic research and industry applications is facing increasing regulatory pressure due to environmental and health concerns. Consequently, there is a growing demand for sustainable solvents, particularly in the enzymatic synthesis and processing of polyesters. Biocatalysts offer a sustainable method for producing these materials; however, achieving high molecular weights often necessitates use of solvents. In this work, we introduce a new class of alternative aprotic solvents with medium polarity produced directly from agricultural waste biomass in up to 83 mol % yield (on xylan basis). The new solvents have a largely unmodified xylose core and acetal functionality, yet they show no peroxide formation and provide reduced flammability risk. We also demonstrate their successful application in enzymatic polycondensation reactions with Candida antarctica lipase B (CaLB). In particular, the solvent dibutylxylose (DBX) outperformed the hazardous solvent diphenyl ether and facilitated polycondensation of the lignin-derived diester pyridine-2,4-dicarboxylate, yielding polyesters with a Mn of >15 kDa. Computational modelling studies provided further insight into the molecular structure and dynamics of CaLB in the presence of new solvents. Lastly, up to 98 wt % of the new xylose acetals were successfully recovered and recycled, further contributing to the sustainability of the overall process.

Computer Modeling Study of the Effects of Radio Frequency EM Radiation on Humans

Computer Modeling Study of the Effects of Radio Frequency EM Radiation on Humans

Influence of natural hyoid bone position and surgical repositioning on upper airway patency: a computational finite element modeling study.

The hyoid bone's inferior baseline position in obstructive sleep apnea (OSA) has led to surgical hyoid repositioning (SHR) treatment, yet outcomes vary widely. The influence of baseline hyoid position (BHP; phenotype) and SHR on upper airway (UA) function remains unclear. We aimed to investigate their impact on the UA using computational modeling. A validated finite element model of the rabbit UA was advanced and used to simulate changes in BHP and SHR, alone and in combination. The hyoid was displaced in cranial, caudal, anterior, anterior-cranial, and anterior-caudal directions from 1 to 4 mm. Model outcomes included UA collapsibility, measured using closing pressure (Pclose), cross-sectional area (CSA), and soft tissue mechanics (displacement, stress, and strain). Graded BHP increments increased Pclose for all directions and up to 29%-43% at 4 mm (relative to the original BHP). Anterior-based SHR decreased Pclose (approximately -115% at 4 mm) and increased ΔCSA (approximately +35% at 4 mm). Cranial SHR decreased ΔPclose (-29%), minimally affecting CSA. Caudal SHR increased ΔPclose (+27%) and decreased ΔCSA (-7%). Anterior-cranial and anterior-caudal SHR produced the highest stresses and strains. SHR effects on UA outcomes were dependent on BHP, with more caudal BHPs leading to less effective surgeries. In conclusion, BHP (phenotype) and SHR both alter UA outcomes, with effects dependent on hyoid displacement direction and magnitude. BHP influences the effectiveness of SHR in reducing UA collapsibility. These findings provide further insights into the hyoid's role in UA patency and suggest that considering the hyoid's baseline position and surgical repositioning direction/increment may help improve hyoid surgeries for OSA treatment.NEW & NOTEWORTHY Using computational modeling, this study directly shows that any shift from the healthy natural hyoid bone position increases upper airway collapsibility. Surgical hyoid repositioning alters upper airway outcomes in a direction- and magnitude-dependent manner, with its effects influenced by the natural hyoid position. Accounting for both the natural hyoid position and individually prescribed surgical repositioning may enhance upper airway stability and improve outcomes in obstructive sleep apnea (OSA) treatment.

A Computational Perspective into Binding Mechanism of a potent FAK Inhibitor as Anticancer Drug Candidate: Insights from Molecular Dynamics Simulations

Focal adhesion kinase (FAK) is an important non-receptor tyrosine kinase (nRTK) with crucial role in primary cell functions. Fundamental cellular processes, such as migration, adhesion, proliferation, and survival, are regulated by FAK. The tumorigenesis of FAK is very important since it is overexpressed in advanced cancers, causes malignant features and induces cancer metastasis. The available evidence proposes FAK as a promising target for cancer therapy. At the moment, there are no FAK inhibitors (FAKIs) in the market but several small molecule FAKIs have been developed and a few of them entered into clinical studies as anticancer agents. In spite of these achievements, development of selective and potent FAKIs may be partly hampered by the lack of crystallographic or structural data. This limitation could be resolved through proposing robust ligand–protein binding models to design new FAKIs. GSK2256098 is a small molecule ATP-competitive FAKI that undergoes clinical trials as a monotherapy or in combination with other medications against advanced solid tumors. GSK2256098 have been proven to be a selective and potent agent (IC[Formula: see text] 0.4 nM) with respect to other clinical candidates. With regard to appropriate characteristics, this molecule is particularly amenable for performing computational modeling studies. In this study, we try to propose an applicable binding model of GSK2256098 inside the FAK kinase domain. For this purpose, molecular docking, all-atom 200-ns molecular dynamics simulations and free-energy-calculation methods were applied as consecutive modeling techniques. Atomic insight and dynamic evolution of the system were used to attain a stable binding mode and infer chemical interactions of GSK2256098 inside the kinase domain of FAK. Although complementary investigations need to be conducted, obtained results may offer a structural basis for the development of potent and selective FAKIs.

Family Malvaceae: a potential source of secondary metabolites with chemopreventive and anticancer activities supported with in silico pharmacokinetic and pharmacodynamic profiles.

Cancer is the second most widespread cause of mortality following cardiovascular disorders, and it imposes a heavy global burden. Nowadays, herbal nutraceutical products with a plethora of bioactive metabolites represent a foundation stone for the development of promising chemopreventive and anticancer agents. Certain members of the family Malvaceae have traditionally been employed to relieve tumors. The literature concerning the chemopreventive and anticancer effects of the plant species along with the isolated cytotoxic phytometabolites was reviewed. Based on the findings, comprehensive computational modelling studies were performed to explore the pharmacokinetic and pharmacodynamic profiles of the reported cytotoxic metabolites to present basis for future plant-based anticancer drug discovery. All the available information about the anticancer research in family Malvaceae and its cytotoxic phytometabolites were retrieved from official sources. Extensive search was carried out using the keywords Malvaceae, cancer, cytotoxicity, mechanism and signalling pathway. Pharmacokinetic study was performed on the cytotoxic metabolites using SWISS ADME model. Acute oral toxicity expressed as median lethal dose (LD50) was predicted using Pro Tox 3.0 web tool. The compounds were docked using AutoDock Vina platform against epidermal growth factor receptor (EGFR kinase enzyme) obtained from the Protein Data Bank. Molecular dynamic simulations and MMGBSA calculations were performed using GROMACS 2024.2 and gmx_MMPBSA tool v1.5.2. One hundred forty-five articles were eligible in the study. Several tested compounds showed safe pharmacokinetic properties. Also, the molecular docking study showed that the bioactive metabolites possessed agreeable binding affinities to EGFR kinase enzyme. Tiliroside (25), boehmenan (30), boehmenan H (31), and isoquercetin (22) elicited the highest binding affinity toward the enzyme with a score of -10.4, -10.4, -10.2 and -10.1Kcal/mol compared to the reference drug erlotinib having a binding score equal to -9Kcal/mol. Additionally, compounds 25 and 31 elicited binding free energies equal to -42.17 and -42.68Kcal/mol, respectively, comparable to erlotinib. Overall, the current study presents helpful insights into the pharmacokinetic and pharmacodynamic properties of the reported cytotoxic metabolites belonging to family Malvaceae members. The molecular docking and dynamic simulations results intensify the roles of secondary metabolites from medicinal plants in fighting cancer.

In Vitro and In Vivo Biological Evaluation of Novel 1,4-Naphthoquinone Derivatives as Potential Anticancer Agents.

A novel library of naphthoquinone derivatives (3-5 aa) was synthesized and evaluated for their anticancer properties. Specifically, compounds 5 i, 5 l, 5 o, 5 q, 5 r, 5 s, 5 t, and 5 v demonstrated superior cytotoxic activity against the cancer cell lines that were studied. All the studied compounds exhibited a higher selectivity index (SI) and a favourable safety profile than the standard drug doxorubicin. Notably, compound 5 v displayed a greater cytotoxic effect on MCF-7 cells (IC50=1.2 μM, and 0.9 μM at 24 h and 48 h, respectively) compared to the standard drug doxorubicin (IC50=2.4 μM, and 2.1 μM at 24 h and 48 h, respectively). To further investigate the mechanism of cytotoxic effect, additional anticancer studies were conducted with 5 v in MCF-7 cells. The studies are including morphological changes, AO/EB (acridine orange/ethidium bromide) double staining, apoptosis analysis, cell colony assay, SDS-PAGE and Western blotting, cell cycle analysis, and detecting reactive oxygen species (ROS) assay. The findings showed that 5 v triggered cytotoxic effects in MCF-7 cells through the initiation of cell cycle arrest at the G1/S phase and necrosis. In vivo ecotoxicity studies indicated that 5 v had lower toxicity towards zebrafish larvae (LC50=50.15 μM) and had an insignificant impact on cardiac functions. In vivo xenotransplantation of MCF-7 cells in zebrafish larvae demonstrated a significant reduction in tumour volume in the xenograft. Approximately 95 % of the zebrafish larvae with 5 v xenografts survived after 10 days of the treatment. Finally, a computational modelling study was conducted on four protein receptors, namely ER, EFGR, BRCA1, and VEFGR2. The findings highlight the importance of the aminonaphthoquinone moiety, amide linkage, and propyl thio moiety in enhancing the anticancer properties. 5 v exhibited superior drug-likeness features and docking scores (-9.1, -7.1, -8.9, and -10.9 kcal/mol) compared to doxorubicin (-7.2, -6.1, -6.9, and -7.3 kcal/mol) against ER, EFGR, BRCA1, and VEGFR2 receptors, respectively. Therefore, the notable antitumor effects of naphthoquinone derivatives (3-5 aa) suggest that these molecular frameworks may play a role in the development of promising anticancer agents for cancer treatment.

A Methodology to Quantify the Effective Vertical Thickness of Prephonatory Vocal Fold Medial Surface

ObjectiveThe shape of the vocal fold medial surface, particularly its vertical thickness, has been shown in computational and physical modeling studies to be highly influential in regulating glottal closure during phonation. However, because of the difficulty to quantify the vertical thickness in real vocal folds, this influence has often been overlooked in clinical contexts. Therefore, the goal of this study is to present a method to calculate an effective vertical thickness of the medial surface that is predictive of the glottal closure pattern during phonation. MethodsAn effective vertical thickness of the medial surface is calculated as a weighted integral of the medial surface contour along the vertical dimension. The weight is one for the part of the medial surface within a fixed threshold distance from the most medial point, and decays exponentially otherwise. The influence of the threshold distance value on the effective thickness value is investigated. Additionally, the sensitivity of the calculated effective thickness to slight misidentification of the vertical glottal midline is also studied. The methodology is validated on the vocal fold medial surface data from a canine hemilarynx at different levels of thyroarytenoid muscle activation. ResultsFor most threshold distances, the thickness follows an expected sigmoid-like trend with respect to the thyroarytenoid muscle activation level. A threshold distance of 0.05 mm appears optimal as it produced thickness changes in a range comparable to previous computational and experimental studies. The methodology is relatively robust to slight misidentification of the vertical glottal midline. ConclusionsA methodology to estimate the effective vocal fold vertical thickness from medial surface contours is proposed. The methodology can be applied in future studies to correlate medial surface shape to relevant parameters characterizing vocal fold vibration as well as clinical evaluation of treatment effectiveness.

Comparison of Laminar and Turbulent K–Omega Shear Stress Transport Models Under Realistic Boundary Conditions Using Clinical Data for Arterial Stenosis

Abstract Early diagnosis of cardiovascular diseases (CVDs), including arterial stenosis, enables targeted treatments that reduce CVD mortality. It is vital to improve the accuracy of early diagnostic tools. Current computational studies of stenosis use mathematical models, such as laminar and k–omega shear stress transport (SST) models, available in ansys (Fluent and CFX), openfoam, and comsol software packages. Users can adjust boundary conditions, such as inlet velocity and outlet pressure using user-defined functions (UDFs) with different expressions and constant values. However, currently there is no rule over what to impose at these boundaries, and previous studies have used various assumptions, such as rigid artery wall, one-way fluid–structure interaction (FSI) or two-way FSI, and the blood's Newtonian or non-Newtonian material properties. This variety in construction has associated deviations of the models from the clinical data and lessens the value of the models as potential diagnostic or predictive tools for medical practitioners. In this study, we examine arterial stenosis models, with severities of 20%, 40%, and 50%, compared with the healthy artery analyzed in terms of strain energy to the artery wall. Additionally, we investigate elastic walls using one-way FSI, comparing with laminar and k–omega SST. These boundary conditions are based on clinical data. The results regarding the strain energy (mJ) behavior along the artery wall show that the k–omega SST model outperforms the laminar model for short arterial segments and under the Newtonian assumption with a no-slip boundary wall and turbulent flow.

The Use of Organoclays as Excipient for Metformin Delivery: Experimental and Computational Study

This work combines experimental and computational modeling studies for the preparation of a composite of metformin and an organoclay, examining the advantages of a Tunisian clay used for drug delivery applications. The clay mineral studied is a montmorillonite-like smectite (Sm-Na), and the organoclay derivative (HDTMA-Sm) was used as a drug carrier for metformin hydrochloride (MET). In order to assess the MET loading into the clays, these materials were characterized by means of cation exchange capacity assessment, specific surface area measurement, and with the techniques of X-ray diffraction (XRD), differential scanning calorimetry, X-ray fluorescence spectroscopy, and Fourier-transformed infrared spectroscopy. Computational molecular modeling studies showed the surface adsorption process, identifying the clay–drug interactions through hydrogen bonds, and assessing electrostatic interactions for the hybrid MET/Sm-Na and hydrophobic interactions and cation exchange for the hybrid MET/HDTMA-Sm. The results show that the clays (Sm-Na and HDTMA-Sm) are capable of adsorbing MET, reaching a maximum load of 12.42 and 21.97 %, respectively. The adsorption isotherms were fitted by the Freundlich model, indicating heterogeneous adsorption of the studied adsorbate–adsorbent system, and they followed pseudo-second-order kinetics. The calculations of ΔGº indicate the spontaneous and reversible nature of the adsorption. The calculation of ΔH° indicates physical adsorption for the purified clay (Sm-Na) and chemical adsorption for the modified clay (HDTMA-Sm). The release of intercalated MET was studied in media simulating gastric and intestinal fluids, revealing that the purified clay (Sm-Na) and the modified organoclay (HDTMA-Sm) can be used as carriers in controlled drug delivery in future clinical applications. The molecular modeling studies confirmed the experimental phenomena, showing that the main adsorption mechanism is the cation exchange process between proton and MET cations into the interlayer space.

Novel Approaches and Emerging Trends in Hydrotropic Solubilization Technology

Hydrotropic solubilization technology enhances the solubility and bioavailability of poorly water-soluble drugs, a major challenge in pharmaceutical research. This review discusses hydrotropic agents’ structures, the solubilization process, and factors affecting drug solubility. It explores optimizing agent concentrations, the role of computer modeling and QSAR studies, and hydrotropes’ impact on overcoming biological barriers and improving pharmacokinetics and pharmacodynamics. The review highlights hydrotropic compounds’ potential in advancing pharmaceutical formulations and clinical applications.

Understanding the variability of the proximal femoral canal: A computational modeling study.

Statistical shape modeling (SSM) offers the potential to describe the morphological differences in similar shapes using a compact number of variables. Its application in orthopedics is rapidly growing. In this study, an SSM of the intramedullary canal of the proximal femur was built, with the aim to better understanding the complexity of its shape which may, in turn, enhance the preoperative planning of total hip arthroplasty (THA). This includes the prediction of the prosthetic femoral version (PFV) which is known to be highly variable amongst patients who have undergone THA. The model was built on three dimensional (3D) models of 64 femoral canals which were generated from pelvic computed tomography images including the proximal femur in the field of view. Principal component analysis (PCA) was performed on the mean shape derived from the model and each segmented canal. Five prominent modes of variations representing approximately 84% of the total 3D variations in the population of shapes were found to capture variability in size, proximal torsion, intramedullary femoral anteversion, varus/valgus orientation, and distal femoral shaft twist/torsion, respectively. It was established that the intramedullary femoral canal is highly variable in its size, shape, and orientation between different subjects. PCA-driven SSM is beneficial for identifying patterns and extracting valuable features of the femoral canal.