Analysis Method Research Articles

Development of a Spectrophotometric Flow-Based System for the Determination of Total Polyphenol Content in Legume Flours.

Conventional nutritional characterization of legume flours comprises costly and laborious analytical methods for nutrient quantification that establish the quality of seeds, including their macronutrient quantification, fiber, mineral, antioxidant content, and more. The quantification of total polyphenol content (TPC) in legumes is performed using different analytic methods, namely the Folin-Ciocalteu (FC) method, which is lengthy and employs potentially toxic reagents. Additionally, it is time-consuming and prone to human error if carried out in a conventional batch mode. To develop a semi-automatic method for a faster, greener, and more precise TPC quantification, resorting to flow injection analysis (FIA). The development of the FIA method was based on the FC method. The flow manifold was structured by performing an array of preliminary studies, which led to the establishment of the method that displayed the highest sensitivity (highest slope of the calibration curve). The method was applied to determine the TPC in various legume flours. This novel method resulted in a throughput of 1 analysis per minute, allowing to analyze 20 samples in triplicate within an hour, with a LOD of 4.32 mg L-1, a LOQ of 14.4 mg L-1, and an RSD of 4.4%. The results calculated from the proposed FIA method agreed with those of the reference procedure. By using the FIA system, a lower consumption of reagents was observed. Additionally, as there is no need to reach chemical equilibrium, a high throughput has been achieved, resulting in a faster and greener method for the determination of polyphenols in various types of legumes.

Adapting to change: experiences and recommendations from the Pain Management Collaboratory on modifying statistical analysis plans.

Best practices for clinical trials stipulate that statistical analysis plans (SAPs) need to be finalized before initiation of any analysis. However, there is limited guidance about when changes to SAPs are acceptable and how these changes should be incorporated into the research plan with appropriate documentation. We conducted a survey of 12 pragmatic clinical trials (PCTs) in the Pain Management Collaboratory that evaluated nonpharmacological interventions for pain to assess the following SAP information: (1) location of statistical analysis details, (2) types of statistical analyses planned, (3) sponsor requirements, (4) templates used for development, (5) publication plan, (6) changes since trial launch, (7) process of documenting changes, and (8) process of updating the trial registry. All 12 PCTs provided details of their SAPs for the primary outcomes in the institutional review board-approved trial protocol; 8 included plans for secondary outcomes, and 6 included plans for tertiary/exploratory outcomes. Most PCTs made SAP changes after trial initiation, many as a result of COVID-19-related issues. Eleven of the PCTs were actively recruiting participants. Changes were made to sample size, study design, study arms, and analytical methods, all before the data lock/unblinding. In all cases, justification for the changes was documented in the trial protocol or SAP, signed off by the trial biostatistician and principal investigator, and reviewed/approved by an institutional review board, data and safety monitoring board, or sponsor. We recommend that SAP changes can be acceptable up to the time of data lock/unblinding. To maintain full transparency and necessary rigor, clear documentation of such changes should include details, rationale, date(s) such changes were implemented, and evidence of approval by relevant oversight bodies.

Fat extraction methodology can affect the food fatty acid profile: improvement of a protocol more environmentally friendly

Fatty acids (FAs) are biochemical components of food, essential for human health due to their numerous biological functions. However, many of then if consumed in excess can trigger disfunctions/illness. Therefore, analytical methods, such as gas chromatography (GC-FID) are essential for the accurate identification and quantification of FAs, playing an important role in food safety and quality assessment. The aim of this study was to compare two FAs extraction protocols and to adapt, optimize, and validate a new one for food FAs extraction, considering the principles of green chemistry (sustainability and environmentally friendly). The research included four main steps: (A) comparison of two FAs extraction protocols for Gas Chromatography Flame Ionization Detector (GC-FID) analysis; (B) adaptation and optimization of four new extraction protocols; (C) verification of the most promising protocol; and (D) evaluation of the greenness profile. Comparatively, the PE2 protocol detected a greater diversity of FAs and a wider range of medium/long chain saturated fatty acids (SFA), but with divergences from values declared on food labels, mainly in the quantification of unsaturated fatty acids (UFA), unlike PE1, which presented lipid fraction values closer to nutritional information and greater extraction of short/medium chain FAs. The improved protocol, PE6, proved to be more efficient in extracting short, medium, and long chain FAs, as well as having SFA and UFA values closer to nutritional values in different food matrices. Furthermore, PE6 also showed improvements in relation to green chemistry aspects, presenting a higher greenness profile score, which indicates that it is more sustainable and generates less environmental impact. These results underscore the importance and relevance of continuing to develop analytical methods for food that are both effective and environmentally responsible.

Additively Manufactured 3D Clamp-Culture System for the Investigation of Material-Cell Interactions in Multi-Material Hybrid Scaffolds for Musculoskeletal Tissue Defects.

The emergence of hybrid scaffolds, blending biomaterials with diverse properties, offers promise in musculoskeletal tissue engineering. However, a need for invitro platforms investigating biological behavior and the interplay of different load-bearing and colonizable synthetic bone substitute materials remains. Herein, we present a novel, in-house producible, and scalable clamp culture system designed for facile invitro analysis of interactions between biomaterials, hydrogels, and cells. The system, constructed here from an exemplary 3D-printable polymer and photopolymerizable hydrogel using a widely available benchtop 3D printer, ensures mechanical stability and protection for the embedded hydrogel via its double-clamp structure, facilitating various analytical methods while preserving culture integrity. Hybrid clamp cultures were additively manufactured from polylactic acid, filled with a bone precursor cell-laden methacrylate gelatin hydrogel, cultured for 14 days, and analyzed for cell viability, mineralization, and osseous differentiation. Results indicate no adverse effects on osteogenic differentiation or mineralization compared to conventional droplet cultures, with enhanced cell viability and simplified handling and downstream analysis. This system demonstrates the potential for robust experimentation in tissue engineering and is adaptable to various plate formats, and thus highly suitable for the investigation of biomaterial-cell interactions and the development of implants for musculoskeletal tissue defects.

Simultaneous Determination of Methotrexate and 7-Hydroxy-Methotrexate by UHPLC-MS3 Assay Coupled With Multiple Stage Fragmentation to Enhance Sensitivity.

A selective ultra-high performance liquid chromatography tandem mass spectrometry cubed (UHPLC/MS3) assay for simultaneous determination of methotrexate (MTX) and 7-hydroxy-methotrexate (7-OH-MTX) in human plasma was developed and validated. After protein precipitation with methanol, chromatographic separation of MTX, MTX-d3, and 7-OH-MTX was performed on a Waters AcQuity UPLC-BEH column (2.1×50mm I.D., 1.7µm) with gradient elution. MRM3 transition was used for the detection of MTX (m/z 455.2→308.0→175.1) and 7-OH-MTX (m/z 471.3→191.0→148.1). The linear range of UHPLC/MS3 assay for the determination of MTX and 7-OH-MTX was 0.5-300ng/mL (R2≥0.99) and 5-1500ng/mL (R2≥0.99), respectively. The enhanced selectivity and sensitivity are the novelties of the developed UHPLC/MS3 assay. The analytical method was successfully applied to simultaneous determination of MTX and its major metabolite 7-OH-MTX in real human plasma samples.

Assessing the Effect of Minimally Invasive Lipid Extraction on Parchment Integrity by Artificial Ageing and Integrated Analytical Techniques.

To assess the short and long-term effect of a newly developed minimally invasive lipid extraction method on parchment, sacrificial pieces of parchments were subjected to artificial ageing and investigated using various analytical methods. Lipids were extracted using our novel vacuum-aided extraction method and characterised by high-temperature gas chromatography (HTGC-FID). Lipids were identified as arising from degraded animal fats. The physical, molecular, and mechanical properties of the parchment samples before/after lipid extraction, and before/after ageing were assessed using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR) and pure shear single notch fracture testing. SEM imaging allowed for an assessment of potential structural changes of the collagen fibres while FTIR was used to investigate the possible molecular changes indicated by changes in amide I and II bands. Mechanical tests were used to record the changes in brittleness and stiffness occurring in the materials through lipid extraction and ageing. The multimodal investigation did not highlight measurable changes in the structural, molecular, and mechanical properties of the lipid-extracted parchment, thus indicating the suitability for the minimally invasive lipid extraction method to be applied to historical parchments.

Facile synthesis and fabrication of Mg2SnO4/carbon black as a sustainable electrode for determination of non-steroidal anti-inflammatory drug-flutamide

The accumulation of hazardous pharmaceutical wastes in aquatic organisms, particularly nonsteroidal anti-inflammatory drug molecules, has severe toxicological consequences for both aquatic life and humans. To protect the environment, it is essential to develop a highly efficient device with dual-purpose capabilities for drug detection while minimizing catalyst expenditure. In this work, we explored a simple and effective design for fabricating a magnesium stannate combined with carbon black (Mg2SnO4/CB) nanocomposite as a cost-effective, sustainable electrode material for the electrochemical detection of flutamide (Flu). The Mg2SnO4/CB nanocomposite was synthesized through a simple hydrothermal process followed by sonication. Various analytical methods were used to determine its physico-chemical characteristics. The electrochemical efficiency of Mg2SnO4/CB/GCE was evaluated by detecting Flu, showing a remarkable linear range from 0.6 to 198.4 µM with a sensitivity of 3.91 μA μM−1 cm−2. In addition, the constructed sensor demonstrated excellent selectivity, high repeatability, outstanding reproducibility, and long-lasting stability. The anti-interference experiments yielded a definite current response without any change in peak shifts. Consequently, Mg2SnO4/CB/GCE demonstrated superior performance in determining Flu in human urine and river water samples.

Microplastics detection in some cosmetic samples by Accelerated Solvent Extraction and Micro-FTIR

Worldwide attention is focused on microplastics environmental pollution, primarily for its potential negative effects on biota and human health. It is of great importance to identify standardized analytical methods to have an objective feedback about this concern. The recent regulation regarding the intentionally added microplastics content and the attention for the unintentional microplastics release are the basis of this work, whose topic is the development of an analytical method for microbeads (spheres) and microparticles (fragments) determination in certain cosmetic samples, in particular creamy samples. The method is based on Accelerated Solvent Extraction technique to remove all the sample matrix ingredients. The final suspension was then filtered on silicon membrane, for the following quali-quantitative micro-FTIR analysis, and on glass fibre membranes, for the gravimetric analysis. The method was developed for a theoretical microplastics concentration of 0.025 % (w/w) and allows a good recovery percentage. Working both by gravimetric evaluation and by micro-FTIR analysis gives more confident results and guaranties a proper identification and characterization of the filtered materials.

Green RP-HPLC method for the estimation of carfilzomib in bulk, protein nanocarriers and human plasma: Application of chemometrics and Monte-Carlo simulations

Carfilzomib is a tetrapeptide epoxyketone that has shown potential clinical outcomes in the treatment of multiple myeloma. However, inaccuracies in quantifying such peptide drug products have arisen due to poor stability, low solubility, time-consuming techniques, complex physicochemical properties, and use of non-green solvents with less recyclability. This provides a substantial urge to develop an ecological and sensitive analytical method for quantifying peptide drugs from matrix formulation and biological samples in early as well as lateral stages of product development in pharma industries. As a result, the study aimed to develop a robust ecological method for estimation of carfilzomib via Green RP-HPLC using analytical quality by design (AQbD) paradigms with specific application in protein nanoparticles and biological matrix. Initially, an appropriate wavelength for quantification of carfilzomib was chosen using principal component analysis (PCA) as a chemometric tool.Risk assessment followed by factor screening studies using 8-factor Placket-Burman Design aided in earmarking critical method parameters (CMPs) affecting critical analytical attributes (CAAs). Further, Central Composite Design (CCD) was employed for design space optimisation to demarcate optimum chromatographic conditions, which were corroborated for robustness using Monte-Carlo simulations. The method was validated as per ICH Q2 (R1), followed by quantifying the greenness of the method using Green Assessment tools. The method optimisation resulted in the optimal chromatographic conditions using Green RP-HPLC. The chromatographic system was equipped with a Phenomenex Aeris Peptide-XC C18 column (150 × 4.6 mm × 5 µm), and the mobile phase was composed of isopropanol:methanol:0.1 M PBS (pH 5.5 adjusted using 0.1 % formic acid) (35:45:20v/v), with a 1 ml/min flow rate at a 210 nm ʎmax. The optimised chromatographic conditions resulted in a short retention time (RT) of 4.95 mins, 0.87 tailing factor (TF), 4,875,122 peak area (PA), and 8995 theoretical plate count (TPC). The method demonstrated linearity in a wide range of concentrations (0.1–20 µg/ml) with a correlational coefficient of 0.997 and < 2 % RSD. The method unearthed a high precision rate with more than 95 % of drug recovery in protein nanoparticles and human plasma, thereby confirming the accuracy and sensitivity of the developed method. Chemometrics and Monte-Carlo simulations ratified the robustness and sensitivity of the developed analytical method of Carfilzomib with established greenness and a high degree of practical utility in protein-based nano formulations and human plasma matrix for life cycle product development.

Inklusi Keuangan dan Efektifitas Kebijakan Moneter : Studi Kasus Negara Indonesia dan Malaysia

Financial inclusion, defined as access and use of formal financial products and services by individuals and companies, has become a major focus in Indonesia and Malaysia in recent years. Authorities in both countries have implemented various policies and programs to increase financial inclusion, hoping to provide economic benefits, namely reducing inflation. The aim of this research is to analyze the influence of financial inclusion, exchange rates, interest rates, broad money, and GDP on inflation in Indonesia and Malaysia. The data used in this research is secondary data ranging from the period 2013Q1 to 2022Q4. The analytical method used in this research is the Vector Error Correction Model (VECM). The conclusion of this research states that the financial inclusion variable has a negative influence on inflation in Indonesia with a VD contribution at the end of the period of 29.37%, while in Malaysia Financial Inclusion has a positive influence on inflation with a VD contribution at the end of the period of 11.22% . The exchange rate negatively influences inflation in Indonesia and Malaysia with VD contributions at the end of the period of 1.28% and 3.87% respectively. Interest rates have a negative influence on inflation in Indonesia with a VD contribution at the end of the period of 1.71%, while in Malaysia interest rates have a positive influence on inflation with a VD contribution at the end of the period of 13.19%. Broad Money positively influences inflation in Indonesia and Malaysia with VD contributions at the end of the period of 2.27% and 2.57% respectively. GDP has a positive influence on inflation in Indonesia with a VD contribution at the end of the period of 22.01%, while in Malaysia GDP has a negative influence on inflation with a VD contribution at the end of the period of 45.39%.

Release of hydrogen gas from PECVD silicon nitride thin films in cavities of MEMS sensors

In this work we investigate the release of hydrogen gas from PECVD silicon nitride thin films in the cavities of MEMS based inertial sensors. Firstly, material characterization is conducted on two types of PECVD silicon nitride thin films to study the release of hydrogen gas with analytical methods. The release of hydrogen gas from these materials in encapsulated cavities of MEMS sensors, and its influence on the cavity pressure is also investigated experimentally with the help of functional microchips of MEMS based inertial sensors. Based on our findings and reports from other works, we propose steps by which change in the cavity pressure of the investigated microchip occurs over its different fabrication processes. We suggest that hydrogen gas is released form PECVD silicon nitride thin films at high temperatures during wafer bonding, which can then diffuse in cavities at low pressure over the lifetime of the sensor.

Measurement of Acrylamido Tertiary Butyl Sulfonate Polymer Retention on Limestone by Three Methods Under Varying Temperature and Oil Presence

Summary Polymer retention poses a significant challenge in polymer flooding applications, emphasizing the importance of accurately determining retention levels for successful project design. In carbonate reservoirs of the Middle East, where temperatures exceed 90°C, conducting adsorption tests under similar temperature conditions becomes crucial for the precise determination of adsorption values. The choice of analytical method potentially impacts the accuracy of retention measurements from effluent analysis. This study investigates the effect of temperature on the performance of a polymer, specifically its rheological behavior and retention. Rheological and polymer flooding experiments were carried out using an acrylamido tertiary butyl sulfonate (ATBS)-based polymer in formation water (167,114 ppm) at different temperatures (25°C, 60°C, and 90°C) with required oxygen control measures. Dynamic polymer retention was conducted in both the absence of oil (single-phase tests) and the presence of oil (two-phase tests). In addition, different analytical techniques were evaluated, including viscosity measurements, ultraviolet (UV)-visible spectroscopy, and total organic carbon-total nitrogen (TOC-TN) analysis, to determine the most accurate method for measuring the polymer concentration with the least associated uncertainty. Furthermore, the study investigates the effects of these uncertainties on the final dynamic polymer retention values by applying the propagation of error theory. The effluent polymer concentration was determined using viscosity correlation, UV spectrometry, and TOC-TN analysis, all of which were reliable methods with coefficient of determination (R2) values of ~0.99. The study analyzed the effects of flow through porous media and backpressure regulator on polymer degradation. The results showed that the degradation rates were around 2% for flow through porous media and 16% for mechanical degradation due to the backpressure regulator for all temperature conditions. For the effluent sample, the concentration of polymer was lower when using the viscosity method due to polymer degradation. However, the TOC-TN and UV methods were unaffected as they measured the TN and absorbance at a specific wavelength, respectively. Therefore, all viscosity results were corrected for polymer degradation effects in all tests. During the two-phase coreflooding experiment conducted at 25°C, the accuracy of the UV spectrometry and viscosity measurements was affected by the presence of oil, rendering these methods unsuitable. However, the TOC-TN measurements were able to determine effluent polymer concentration and, subsequently, the retention value. Moreover, the use of glycerin preflush to inhibit oil production during polymer injection in the two-phase studies showed that all three methods were appropriate. The error range was obtained using the propagation of error theory for all the methods. Accordingly, it was noted that the temperature did not affect the dynamic retention values in both single-phase and two-phase conditions. The findings of this study highlight that when adequate oxygen control measures are implemented, the temperature does not exhibit a statistically significant impact on the retention of the ATBS-based polymer under investigation. Furthermore, TOC-TN has been identified as the optimal analytical method due to its minimal uncertainties and ease of measuring polymer concentration under varying experimental conditions.

Understanding COVID-19 Vaccine Acceptance Among Iranian Pregnant Women: Insights From a Multicenter Cross-Sectional Study.

Despite significant advancements in COVID-19 vaccine research and development, hesitancy in its acceptance, particularly among pregnant women, is recognized as a health threat. Based on the Health Belief Model, this study aimed to identify the factors influencing vaccine nonacceptance among pregnant women in the cities of Zahedan and Tabriz, Iran. The present research was a multicenter cross-sectional study conducted among pregnant women in two Iranian provinces, Zahedan and Tabriz, covering both high and low fertility regions. The study was conducted from February 2022 to August 2022. The sample size comprised 650 pregnant women attending selected healthcare centers. Data collection tools included questionnaires on sociodemographic characteristics, awareness, vaccine acceptance, and health beliefs related to vaccination. Data were analyzed using descriptive and analytical methods, including Analysis of variance (ANOVA), Independent t-test, and multivariable logistic regression. Among the 650 pregnant women, the vaccine acceptance rate was 47.4% and 52.6% of pregnant women reported vaccine nonacceptance during pregnancy. The logistic regression model indicated that the odds of vaccine acceptance increase with maternal employment (OR = 11.53, 95% CI: 4.81-27.63), higher maternal education levels (OR = 6.97, 95% CI: 3.11-15.63), higher income (OR = 1.60, 95% CI: 1.07-2.55), and increased awareness levels (OR = 1.37, 95% CI: 1.03-1.52). Additionally, the odds of vaccine acceptance increase with increased perceived susceptibility (OR = 2.55, 95% CI: 0.47-3.76), increased perceived benefits (OR = 2.22, 95% CI: 1.06-4.61), increased perceived barriers (OR = 0.42, 95% CI: 0.18-1.12), and increased cues to action (OR = 2.01, 95% CI: 1.03-3.92). Our study underscores the multifaceted nature of COVID-19 vaccine acceptance among pregnant women, with socioeconomic, awareness-related, and psychological factors all playing pivotal roles. These findings can inform targeted interventions and strategies aimed at increasing vaccine acceptance in this vulnerable population, ultimately contributing to enhanced maternal and fetal health during the ongoing pandemic.

The effect of cryogenic treatment on a high Co bearing DIN 1.2888 steel used as die in hot forging process

Abstract Hot work steels used as dies in metal forming processes must endure harsh conditions, typically achieved through a martensitic structure. However, retained austenite can persist after martensitic transformation, negatively impacting mechanical properties. Cryogenic treatment (CT) refines martensite, reduces retained austenite, and increases fine carbide density, thus enhancing performance. DIN 1.2888, a hot work tool steel with high cobalt content (~10%) and low carbon content (~0.2%), is less studied concerning the effects of CT. The objective of this study was to investigate how cryogenic treatment affects the mechanical and microstructural properties of DIN 1.2888 steel. Samples underwent conventional heat treatment (HT) and CT at -100, -140, and -180°C for 6 hours, followed by double tempering. Various analytical methods, including X-ray diffraction (XRD), scanning electron microscopy with energy-dispersive X-ray spectroscopy (SEM-EDS), and Vickers Microhardness tests, were used to examine the samples. Wear mechanisms were evaluated through pin-on-disc tests under different loads, and impact toughness was measured both at room temperature and the working temperature of dies (350°C). Results indicated that lowering the cryogenic treatment temperature resulted in a slight increase in hardness values from 507HV for the heat-treated sample to 529HV for the sample treated at -180°C. Additionally, the impact toughness improved significantly, with values rising from 12.35J for the heat-treated sample to 23.44J at 350°C for the cryogenically treated sample at -180°C. Wear rates also decreased by approximately 50%, particularly at higher cryogenic treatment temperatures. The improvement in wear resistance was attributed to finer carbide precipitation and a more homogeneous distribution of carbides. These findings suggest that deep cryogenic treatment has a positive effect on DIN 1.2888 steel by decreasing retained austenite and increasing fine carbide density, leading to enhanced mechanical properties and extending the lifespan of the steel in die applications.

Free vibration analysis of rectangular plates resting on an elastic foundation

Abstract Rectangular plate on elastic foundations is a common structural form in aerospace fields, while there still lacks a general analytical method for free vibration analysis of this kind of structure. Thus, the extended separation-of-variable method is used to obtain the analytical free vibration solutions for plates with all kinds of homogeneous boundary conditions. The mode functions are assumed to be in separation-of-variable form, and the natural frequencies of two-direction mode functions are mathematically independent. Then, the free vibration solutions are obtained according to the two-direction boundary conditions. The correctness of the present results is verified via numerical comparisons. Parameter study shows that the elastic foundation significantly affects the flexural vibration behaviors of rectangular plates, and the influence is dependent on boundary conditions and mode orders of rectangular plates.

Reliability-based structural-thermal topology optimization of lightweight metal foam skeleton microstructure using the fully analytical adjoint method

Reliability-based structural-thermal topology optimization of lightweight metal foam skeleton microstructure using the fully analytical adjoint method

Tensor based approach for tooth contact analysis of planar and spatial gearing contact

This paper presents a new method for analyzing gear tooth contact, leveraging tensor notation and discrete differential geometry. Existing analytical and numerical methods often face challenges in convergence and computational efficiency. Our proposed approach involves defining a novel tensor notation and applying it to the gear tooth contact kinematics problem. By discretizing the tooth surfaces and using tensor operations, we can accurately determine the kinematics, path of contact, and transmission error of the gear pair. To validate our approach, we compared its results with those obtained from commercial software, KISSsoft and KiMOS. The results demonstrated high accuracy, with mean absolute errors below 0.08 for specific sliding, 0.003 for sliding factor, and 0.1μm for transmission error. Furthermore, we applied our method to analyze non-involute gear types, such as S-gears, pin gearing and cosine gears. Our findings revealed the kinematic performance and contact characteristics of these gear types, providing valuable insights for gear design and optimization. In conclusion, the proposed tensor-based approach offers a promising alternative for gear tooth contact analysis, providing accurate and efficient results for a wide range of gear types.

Regional Analysis and Stage-Specific Incidence of Breast Cancer in Kazakhstan: A Comprehensive Study

BackgroundBreast cancer is the most prevalent oncological pathology in Kazakhstan, ranking among the top three causes of cancer-related deaths in women. The objective of this study is to analyze the incidence of breast cancer, considering factors such as stage, age, sex, and morphological verification in the regional context in Kazakhstan. MethodsThe retrospective study employed descriptive and analytical oncoepidemiological methods. Breast cancer incidence data (2005-2019) were obtained from the Unified Nationwide Electronic Health System (ICD-10 code C50). Demographic data came from the Bureau of National Statistics. Statistical analyses included age-standardized, crude, and age-specific incidence rates, with trend analyses performed using linear regression and the Joinpoint Regression Program to assess average percentage change over time. ResultsThe analysis of breast cancer incidence in Kazakhstan shows significant regional variations and an overall upward trend. Nationally, the age-standardized incidence rate is 40.9 per 100,000, with an annual increase of +1.96%. Early-stage (I-II) breast cancer incidence is rising, particularly in Pavlodar, North Kazakhstan, and Almaty City. In contrast, advanced-stage (III-IV) incidence has generally declined, except in regions like Kostanay, North Kazakhstan, and Atyrau, where late-stage cases are increasing. High morphological verification rates across all regions ensure reliable and accurate diagnostic data. ConclusionThe study reveals a significant increase in early-stage breast cancer diagnoses in Kazakhstan, highlighting the effectiveness of the national screening program. However, regional disparities in late-stage cancer incidence suggest a need for targeted interventions and improved regional healthcare.

Metabolite identification of emerging disinfection byproduct dibromo-benzoquinone in vivo and in vitro: Multi-strategy mass-spectrometry annotation and toxicity characterization

Halobenzoquinones (HBQs) are emerging disinfection byproducts (DBPs) of high toxicity and also are shared active toxic intermediates of multiple halogenated organic pollutants. Due to the strong oxidizing property and electrophilicity, HBQs exhibit extremely diverse metabolism pathways in organisms. The identification of toxic-decisive metabolites is pivotal, albeit challenging, for understanding the toxicity mechanisms of HBQs. We employed dibromo-benzoquinone (DBBQ) as a representative HBQ, and established a systematic analytical strategy using high-resolution mass spectrometry, which collectively coupled suspect screening (SS), mass defect filtering (MDF), product ion filtering (PIF), isotopic signature filtering (ISF), and molecular networking (MN). As a result, 20 biotransformation products of DBBQ were identified in vivo and in vitro, involving metabolism reactions such as hydroxylation, methylation, methoxylation, acetylation, sulfonation, glucuronidation, glutathionylation, dimerization, and conjugation with amino acids or fatty acids. Quantitative structure-activity relationship (QSAR) analysis and cytotoxicity experiments consistently demonstrated the significantly high toxicity of the fatty acid conjugate compared to the parent compound DBBQ and other metabolites, pinpointing the important role of the fatty acid conjugation in determining the metabolism and toxicity of HBQs. The research conducted a comprehensive evaluation of the metabolism of a typical HBQ with the combination of multiple analytical and toxicity characterization methods, therefore screen out the most important metabolism pathway of HBQs.

Advancing analytical and graphical methods for binary and ternary mixtures: The toxic interactions of divalent metal ions in human lung cells

Advancing analytical and graphical methods for binary and ternary mixtures: The toxic interactions of divalent metal ions in human lung cells