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Pancreatic cancer is a devastating malignancy in great need of new and more effective treatment approaches. In recent years, studies have indicated that nutritional interventions, particularly nutraceuticals, may provide novel avenues to modulate cancer progression. Here, our study characterizes the impact of ω-3 polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), as a nutraceutical intervention in pancreatic cancer using a genetically engineered mouse model driven by KrasG12D and Trp53R172H. This model closely resembles human pancreatic carcinogenesis, offering a disease relevant platform for translational research. Our findings showed that ω-3 PUFAs intervention (using a diet supplemented with 6% cod liver oil) significantly reduced tumor volume as well as lung and liver metastasis and a trend towards improved survival rate compared to control treated mice. This antitumoral effect was accompanied by distinct changes in tumor membrane fatty acid profile and eicosanoids release. Further, the EPA and DHA intervention also reduced malignant histological parameters and induced apoptosis without affecting cell proliferation. Of note is the significant reduction in tumor fibrosis that was associated with decreased levels of Sonic Hedgehog (SHH), a major ligand controlling this cellular compartment in pancreatic cancer. All together our results demonstrate the impact of EPA and DHA as antitumor regulators in pancreatic cancer, suggesting potential for ω-3 PUFAs as a possible antitumoral dietary intervention. This research opens new avenues for integrating nutraceutical strategies in pancreatic cancer management.
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Fatty acid (FA), tocopherol, and phytosterol profiles are used in avocado oil purity standards. However, blends with other oils can mimic the profile of pure avocado oil, resulting in similar ranges for these molecules. Therefore, fatty alcohol esters (FAEs) uniquely of Persea spp. were assessed as complementary markers in the chemical profile of pure avocado oil. Utilizing HPLC-TOF-MS and UPLC-MS/MS for identification and HPLC-DAD-ELSD for quantification, major FAEs were analyzed in nine cultivars. Major FAEs included Persin (20-48%), AcO-avocadyne (11-44%), Persenone A (12-30%), and AcO-avocadene (3-24%). Metabolic balance between the main FAs (C18:1n-9, C16:0, C16:1n-9, and C18:2n-6), vaccenic (C18:1n-7), two C17-FAs, and low levels of C18:3n-3 and stearic acid marked the pattern. Relationships between avocado FAs and FAEs were assessed, reinforcing the relevance of both metabolite groups to the fingerprinting of avocado oil and as novel composition biomarkers.
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This in vitro research assessed the influence of the instrument kinematics (rotary and reciprocating) and the apical preparation limit on the root canal disinfection and apical bacterial extrusion. After 21 days of Enterococcus faecalis biofilm formation in 72 mesial root canals of mandibular molars, the root canals were distributed into 2 groups (n = 36) according to the systems used for preparation: ProDesign S and Reciproc. The groups were redistributed according to the limit of apical preparation (n = 11): (a) 1 mm up to the apical foramen (TL-1); (b) at the apical foramen (TL = 0); (c) 1 mm beyond the apical foramen (TL + 1). After preparation, the remaining biofilm adhered to the dentin walls at the apical third was removed by sonication. The aliquots of bacterial suspension released, and the irrigating solution leaked through the apical foramen during preparation were plated for colony-forming units (CFUs) counting. Data were statistically assessed by the Kruskal-Wallis and Dunn tests (α = 5%). Both systems promoted decontamination of the apical third, regardless the limit of apical preparation (p > 0.05). A larger quantity of bacteria was extruded from the root canals prepared 1 mm beyond the apical foramen, regardless the instrumentation kinematics (p < 0.05). The apical third of the root canal was efficiently decontaminated after preparation, regardless the instrumentation kinematics and the apical limit. However, a larger quantity of bacterial extrusion was observed when preparation was performed beyond the anatomical root canal limits.
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Metabolic and bariatric surgery (MBS) has been associated with weight reduction and obesity complications improvement. However, there is no clear evidence of the extent and consistency of the effects of this procedure on rheumatic diseases. This study aims to conduct a meta-analysis to address the impact of MBS on rheumatic diseases. We searched PubMed, Cochrane, and Embase for studies reporting the prevalence of rheumatic diseases, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and the medication use after MBS. We conducted a random-effects meta-analysis using odds ratios (OR) and mean differences (MD) with 95% confidence intervals (CI). P-values < 0.05 were considered statistically significant. We included 28 studies comprising 43,421 patients, with 13,347 patients with rheumatic diseases. The prevalence of osteoarthritis (OA), rheumatoid arthritis, and psoriatic arthritis was significantly reduced after MBS (OR 0.20; 95% CI 0.12 to 0.33; P = 0.01). The WOMAC index for patients with OA had a statistically significant overall reduction after MBS at 6 months (MD - 20.60 points; 95% CI - 28.73 to - 12.47; P < 0.01) and at 12 months (MD - 15.88 points; 95% CI - 19.09 to - 12.66; P < 0.01). Medication use significantly decreased after MBS, both at the follow-up beyond 2 years (OR 0.49; 95% CI 0.35 to 0.69; P < 0.01) and up to 2 years (OR 0.32; 95% CI 0.15 to 0.69; P < 0.01). In this meta-analysis, we found a significant decrease in the prevalence of rheumatic diseases, improvements in the WOMAC index, and reduced medication use among patients undergoing MBS.
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A cystine-dense peptide (CDP) named TfRB1 was identified for its ability to bind to the transferrin receptor (TfR). CDPs are stabilized by their disulfide bonds, and variants of TfRB1 - specifically TfRB1G1, TfRB1G2, and TfRB1G3 - are explored for their potential to transport molecules across the blood-brain barrier (BBB) into the central nervous system (CNS). This study employed molecular modeling and dynamics simulations to characterize the interactions between these TfRB1 variants and TfR. Binding free energy calculations showed a strong correlation with experimental binding affinities of -10.99 kcal/mol for TfRB1G2 and -13.18 kcal/mol for TfRB1G3, with a relative error of 1.98%. The key forces driving these interactions include electrostatic and van der Waals forces, with mutations in TfRB1G3 (T9M and A13D) enhancing its binding affinity through improved interactions with residues such as Arg633. The free energy landscape analysis revealed that TfRB1G3 maintains the N-terminal residues of TfR in an α-helical conformation, unlike TfRB1G2. Per-residue free energy decomposition identified key residues - Leu619, Arg629, Tyr643, and Phe650 - as crucial for TfR binding, underscoring their competitive nature with transferrin. Additionally, Glu612, which is favorable for binding in TfRB1G2, becomes unfavorable in TfRB1G3. Conversely, Arg633 shifts from unfavorable in TfRB1G2 to favorable in TfRB1G3, compensating for the loss of favorable interaction with Glu612. These findings provide valuable molecular insights into the TfRB1 peptides' potential as drug carriers, highlighting their capability to deliver molecules to the CNS and compete with transferrin for BBB transport.
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INTRODUCTION: Diabetes mellitus is a complex disease in terms of its causes and pathophysiological processes, it produces a significant impact on health and leads to complications that are difficult to manage. CONTENT: This review summarizes and analyzes recent advances in the understanding of the mechanisms of diabetes mellitus and how apitherapy affects them. Also present the available clinical evidence on its application. SUMMARY: Apitherapy (complementary-integral use of beehive products) is a potentially useful therapeutic system with a significant level of evidence. This review shows and analyzes the preclinical and clinical evidence on the use of apitherapy in diabetes mellitus. OUTLOOK: Apitherapy shows significant effects on epigenetics, chronic inflammation, oxidative stress, metabolic control, dysbiosis, premature cell death and tissue remodeling. Clinical evidence shows an impact on these mechanisms. Apitherapy is a very useful complementary medicine in the treatment of diabetes mellitus.
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Stress occurs as a reaction to mental and emotional pressure, anxiety, or scarring. Chronic stress is defined as constant submission to these moments. It can affect several body systems, increase blood pressure, and weaken immunity, thereby interfering with physiological health processes. Thus, this study aims to evaluate the effects of chronic stress on the redox status and histomorphological parameters of salivary glands. Thirty-two albino Wistar male rats were randomly divided into two groups: chronic stress and control. Chronically stressed animals were subjected to a restraint protocol by introducing them into a polyvinyl tube for 4 hours daily for 28 days, allowing immobilization of their movements. Subsequently, the animals were euthanized for further collection of the parotid and submandibular salivary glands. The redox state of the glands was evaluated using the antioxidant capacity against peroxyl radicals (ACAP) and thiobarbituric acid reactive substances (TBARS) assays. Histological analysis was performed through morphometry of the tissues stained with hematoxylin and eosin and histochemical through picrosirius red staining. Both the parotid and submandibular glands of stressed rats exhibited oxidative stress due to a decrease in ACAP and an increase in TBARS levels. However, the parotid glands are more susceptible to harmful changes in the tissue, such as an increase in the stromal area and in the collagen area fraction, decrease in the acinar area, and smaller size of the acinus and ducts. Our results suggest that chronic stress may cause harmful modulation of the redox state of the salivary glands, with different histological repercussions.
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Oxidación-Reducción , Estrés Oxidativo , Glándula Parótida , Ratas Wistar , Estrés Psicológico , Glándula Submandibular , Sustancias Reactivas al Ácido Tiobarbitúrico , Animales , Masculino , Ratas , Estrés Psicológico/patología , Estrés Psicológico/metabolismo , Glándula Submandibular/patología , Glándula Submandibular/metabolismo , Glándula Parótida/patología , Glándula Parótida/metabolismo , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo , Glándulas Salivales/patología , Glándulas Salivales/metabolismo , Restricción Física , Antioxidantes/metabolismoRESUMEN
Ascites syndrome (AS) is a deadly condition in fast-growing chickens, preceded by pulmonary arterial hypertension (PAH), where the angiotensin II type 1 receptor (ATR1) plays a role. We investigated whether allicin (ALLI), a garlic derivative, could (a) interact with broiler ATR1, (b) affect ascites-related traits [haematocrit content (Hct%), blood oxygen saturation (SaO2), and the right-to-total ventricular weight ratio (RV:TV)], (c) modify ATR1 expression in the lung, heart, and liver, alongside ascites mortality and growth performance in Ross 308 broilers raised at high altitude and under cold temperatures promoting PAH/AS. Three groups (n = 70 each) were studied: 0-ALLI (untreated), 1-ALLI (allicin 1 mg/kg body weight/daily at 14-27 days of age by oral-oesophageal route), and 2.5-ALLI. After 3 to 6 weeks, Hct%, SaO2, RV:TV ratios, and ATR1 expression in the lung, heart, and liver, were evaluated. Weekly productive performance and AS mortality were recorded. Molecular dockings and dynamic simulations predicted that ALLI might inhibit broiler ATR1 in a transitory manner. At 42 days of age, birds in the 2.5-ALLI group exhibited lower Hct% and lower RV:TV values, while ALLI marginally enhanced SaO2. ATR1 expression in the 1-ALLI and 2.5-ALLI groups was higher (i.e., restored) in the lungs and heart, respectively, but not in the liver compared with the untreated group. Productive performance remained unaffected by ALLI, and 2.5-ALLI provided a protection of 4.3% against ascites mortality. In conclusion, 2.5-ALLI mitigated PAH/AS traits in the lungs and heart without compromising broiler productive performance. Further studies adjusting ALLI doses and combinations are warranted.
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We investigate the dynamics of two-dimensional assemblies of rod-shaped magnetic colloids under the influence of an external rotating magnetic field. Using molecular dynamics, we simulate the formation of patterns that emerge based on the synchronization degree between the magnetic rods and the rotating field. We then explore the structural and dynamic characteristics of the resulting steady states, examining their evolution as a function of changes in the rods' aspect ratio, the strength of the external magnetic field, and its rotation frequency. Three distinct synchronization regimes of the rods with the magnetic field are clearly observed. A detailed set of phase diagrams illustrates the complex relationship between the magnitude of the external magnetic field and its rotation frequency and how these parameters govern the formation of unique self-organized structures.
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Low-energy light ion beams are an essential resource in lithography for nanopatterning magnetic materials and interfaces due to their ability to modify the structure and properties of metamaterials. Here we create ferromagnetic/non-ferromagnetic heterostructures with a controlled layer thickness and nanometer-scale precision. For this, hydrogen ion (H+) irradiation is used to reduce the antiferromagnetic nickel oxide (NiO) layer into ferromagnetic Ni with lower fluence than in the case of helium ion (He+) irradiation. Our results indicate that H+ chemical affinity with oxygen is the primary mechanism for efficient atom remotion, as opposed to He+ irradiation, where the chemical affinity for oxygen is negligible.
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BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading chronic liver disease worldwide, with alarming prevalence reaching epidemic proportions. AIMS AND METHODS: The objective of this study is to provide a comprehensive review of the latest blood proteomics studies on MASLD and metabolic dysfunction-associated steatohepatitis (MASH), with emphasis on fibrosis. Furthermore, our objective is to conduct an analysis of protein pathways and interactions by integrating proteomics data using functional enrichment analysis of the deregulated proteins. RESULTS: Notwithstanding the considerable discrepancies in the methodology and the number of proteins examined in the circulation, the analysis reveals a consistent pattern among the list of proteins that are decreased or increased in the blood of the affected patients. The relevant biological processes (BP) associated with down- and upregulated proteins are high-density lipoprotein remodelling and complement activation, respectively. The protein families identified include not only those expected to be involved in the immune system and cell adhesion and migration but also ligands of glycoproteins expressed in cells that have been subjected to stress and proteins containing the Sushi domain. CONCLUSIONS: The application of cutting-edge methodologies to investigate the blood proteome in MASH is yielding insights that facilitate the elucidation of disease mechanisms and the identification of optimal noninvasive biomarkers. However, several challenges remain to be addressed in future research, including the generalisation of results on a global scale, the optimisation of analytical technologies and the implementation of large longitudinal studies to gain insights into the molecular mechanisms that underpin the development of advanced disease.
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Mpox is a zoonotic viral disease caused by the Monkeypox virus (MPXV). Human cases have been mainly restricted to the African continent until the worldwide multi-country outbreak unfolded in 2022. We reconstructed epidemiological links of 53 MPXV infections using genomic epidemiology in Rio Grande do Sul State, southern Brazil, during 2022 and 2023. We detected five well-supported clades, three representing local transmission chains that were mostly restricted to the 2022 virus spread, one supported year-long maintenance encompassing samples from 2022 and 2023, and one new importation from Europe in 2023. Our results provide new insights into the geographic extent of community transmission and its association with viral diversity during the more pronounced 2022 mpox upsurge and during the following lower incidence phase. These findings highlight the power of continued genomic surveillance to uncover hidden transmission chains to understand viral dynamics and inform public health responses. The detection of sustained transmission in the state is important to guide targeted control measures to curtail further community and international transmission and highlight the need for maintaining genomic surveillance efforts.
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In this study, we evaluated the impact of Epigalocatechin-3-gallate (EGCG) on S. mutans biofilm development for 24 and 46 h using high-resolution confocal laser scanning microscopy. EGCG treatment led to the formation of interspaced exopolysaccharide (EPS)-microcolony complexes unevenly distributed on the surface of hydroxyapatite disc, forming a thinner and less complex biofilm structure with significantly reduced biomass, matrix volume, and thickness compared to the NaCl treated group (negative control). At 46 h, the biofilm of the EGCG-treatment group failed to form the bacterial-EPS superstructures which is characteristic of the biofilm in the negative control group. EGCG treatment seems to significantly delay biofilm development, with the 46 h biofilm in the EGCG treatment group resembling the negative control group at 24 h. EGCG topical treatments impaired S. mutans biofilm initial growth and maturation, suggesting its potential to be used as a preventive agent against dental caries.
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This study explored the effects of melatonin on cardiac and vascular function, and redox homeostasis in model PAH. Male Wistar rats were divided into: control (CTR), monocrotaline [MCT (60 mg/kg, single dose i.p)], monocrotaline + sildenafil [MCT + SIL (50 mg/kg/day)], and monocrotaline + melatonin [MCT + MEL (10 mg/kg/day)]. This protocol lasted 21 days. Echocardiographic, morphometric, histological, vascular reactivity, and oxidative/nitrosative stress analyses were performed. The reduced diastolic function and AT/ET ratio in the MCT group were partially attenuated by melatonin and sildenafil treatment (p < 0.05). Increased RV hypertrophy and pulmonary congestion were reduced by both treatments (p < 0.05). MCT-induced pulmonary arteriolar muscle layer hypertrophy was also reduced by both treatments (p < 0.05). MCT and MCT + SIL present diminished vasorelaxation as compared to control (p < 0.05). Augmented oxidative/nitrosative stress and reduced glutathione-s-transferase activity in MCT were mitigated by both treatments (p < 0.05). Then, melatonin was as effective as sildenafil against PAH-induced oxidative stress and pathological vascular remodelling.
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In July 2022, adult female Culicoides were collected from San Buenaventura (54 specimens) and Urique (3 specimens) in Chihuahua, Mexico. Culicoides reevesi and Culicoides debilipalpis were new records for the state, with C. reevesi also being a first for Mexico. The study highlights DNA barcode identification challenges and emphasizes the need for ongoing surveillance along the Mexico-USA border.
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In the quest to harness the power of quantum computing, training quantum neural networks (QNNs) presents a formidable challenge. This study introduces an innovative approach, integrating the Bees Optimization Algorithm (BOA) to overcome one of the most significant hurdles-barren plateaus. Our experiments across varying qubit counts and circuit depths demonstrate the BOA's superior performance compared to the Adam algorithm. Notably, BOA achieves faster convergence, higher accuracy, and greater computational efficiency. This study confirms BOA's potential to enhance the applicability of QNNs in complex quantum computations.
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This paper deals with the trapping of a particle diffusing in a cylindrical cavity by two circular absorbing spots of arbitrary radii located in the centers of the cavity bases. The focus is on the mean particle lifetime, which is its mean first-passage time to one of the spots. When the spots are small and their radii are well below the cavity radius, this time can be analyzed using the narrow escape (NE) theory, which describes it as a function of the spot radii and the only parameter of the cavity, its volume, independent of the cavity shape and the particle initial position. We derive an approximate analytical solution for the mean particle lifetime that goes beyond the scope of the NE theory. In particular, our solution shows how this mean lifetime depends on the cavity shape, i.e., its length and radius, the particle initial position in the cavity, and the spot radii, which can be arbitrary. It reduces to the NE solution, as the spot radii tend to zero. To check the accuracy of our approximate result, we determine the mean lifetimes from three-dimensional Brownian dynamics simulations. The comparison shows excellent agreement between the theoretical predictions and simulation results when the initial distance from the particle to both cavity bases exceeds the cavity radius.
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A new strategy is proposed for second-order data fusion based on the simultaneous modeling of two data sets using the multivariate curve resolution-alternating least-squares (MCR-ALS) model, applying a new constraint during the ALS stage, called "Proportionality of Scores". This approach allows for the fusion of data from different sources, without requiring common dimensionality, and enables the application of specific constraints to each data set. This strategy was applied to the determination of five pharmaceutical contaminants (naproxen, danofloxacin, ofloxacin, sarafloxacin, and enoxacin) in environmental water samples, by fusing two sets of excitation-emission fluorescence matrices, measured before and after photochemical derivatization. The predictive performance of the fused model was compared to individual PARAFAC models built for each fluorescence data set, showing that data fusion significantly increases precision and accuracy, as indicated by the elliptical joint confidence region test. Data fusion allowed improvement of relative errors of prediction, from 13-32% to 8-15% in validation samples and from 25-121% to 13-20% in real samples. The advantages of data fusion were evident in both cases, particularly in instances of substantial signal overlap between analytes or the presence of uncalibrated interferents with similar profiles, as demonstrated by the superior predictive capacity achieved through the proposed strategy.
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OBJECTIVES: To evaluate urinalysis parameters useful for identifying mixed cultures in urine culture using an automated urinary particle analyzer to assess quality indicators (QIs) for urine sample contamination. METHODS: A retrospective observational cross-sectional study was conducted with 2,527 urine samples from patients of a quaternary hospital in Brazil. Urine samples were processed simultaneously in Sysmex UF-5000 flow cytometry analyzer (urinalysis) and MALDI-TOF (culture). RESULTS: For all samples, a cutoff of 123.8 bacteria/µL was established to discriminate culture-negative specimens. ROC curve indicated the following cutoffs for females and males, respectively: 193.65 and 23.55 bacteria/µL, and 21.35 and 5.05 squamous epithelial cells (SEC)/µL, with the latter two related to scenarios of sample contamination/colonization through mixed cultures. Performing univariate logistic regression, we found a 2.78 (CI95â¯%: 2.12-3.65) times higher chance of probable mixed culture when SEC values were above the cutoffs for each sex, and 6.91(CI95â¯%: 4.56-10.47) times for bacteria. For multivariate logistic regression, the OR values were 1.62 (CI95â¯%: 1.21-2.15) and 5.82 (CI95â¯%: 3.77-8.98), respectively. CONCLUSIONS: The fluorescent flow cytometry analyzers could efficiently identify urinary bacteria counts associated with contamination/colonization scenarios using the cutoffs of 21.35 SEC/µL for women and 5.05 SEC/µL for men. The cutoffs for bacteria/µL (193.65 for females and 23.55 for males) indicated that the presence of bacteria in male samples may be more associated with urinary tract infections (UTIs), while in female samples, it may be associated with either UTIs or contamination/colonization scenarios. This makes the analyzer a helpful tool as QI of sample contamination in urine cultures.
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BACKGROUND: The most commonly used classification for proximal fifth metatarsal fractures has not shown good reproducibility. The aim of this study was to evaluate the intraobserver and interobserver agreement of a new classification system for such fractures. METHODS: The study involved the development of a novel classification system that categorized these fractures into 2 main types and 2 subtypes. This cross-sectional study included a total of 52 cases that were retrospectively collected to assess the reliability of this system. These cases were then evaluated by 3 independent foot and ankle surgeons who classified the fractures based on the newly established classification system. After 10 months, the same evaluators classified the fractures again. The level of agreement among the evaluators, both internally and externally, was assessed using the kappa coefficient, following the criteria established by Landis and Koch. This framework categorizes agreement levels as slight (0.00-0.20), fair (0.21-0.40), moderate (0.41-0.60), substantial (0.61-0.80), or almost perfect (0.81-1.00). RESULTS: Fifty-two fractures were detected, and 312 evaluations were carried out. The interobserver agreement was substantial when assessing the 2 main types, with a κ value of 0.73, and remained substantial even when considering the subtypes, with a κ value of 0.67. Similarly, the intraobserver agreement demonstrated substantial outcomes when evaluating the 2 main types, with a κ value 0.79. It maintained its significance when including the subtypes, with a κ value 0.77. CONCLUSION: Lawrence and Botte's classification identifies 3 primary zones and exhibits moderate interobserver agreement. In contrast, the newly proposed system focuses on only 2 main zones and shows better interobserver agreement. The present study introduces a more precise and reproducible framework that reveals consistency among various observers, including the same observer. This framework may be beneficial for biomedical research as it enhances the ability to compare results across different studies.