Search Results (454)

Nonparametric inference for residual-life functionals is a fundamental problem in mathematical statistics, reliability theory, and survival analysis, particularly in studies with limited sample sizes where empirical plug-in estimators may exhibit substantial sampling variability. In comparative lifetime analysis, additional qualitative information is often available regarding the relative behavior of two populations; however, such information is frequently too weak to justify classical stochastic dominance assumptions. Stochastic precedence provides a natural and interpretable framework for representing this partial ordering through a pairwise probabilistic constraint. This paper develops a constraint-adjusted nonparametric inference framework for estimating the mean residual life (MRL) and quantile residual life (QRL) functions under stochastic precedence information. The proposed approach replaces the ordinary empirical distribution function in standard residual-life plug-in estimators with a constraint-adjusted empirical distribution function that enforces the stochastic precedence relation at the sample level. The adjustment is governed by a data-driven scaling factor and is asymptotically negligible, thereby preserving the large-sample behavior of the ordinary empirical estimators while incorporating meaningful structural information in finite samples. Strong consistency of the proposed MRL and QRL estimators was established under mild regularity conditions. A Monte Carlo study based on Weibull and gamma lifetime models demonstrates that in the simulation settings considered, the proposed estimators provide improved finite-sample stability and generally achieve smaller mean squared errors than their ordinary empirical counterparts, especially for small and moderate sample sizes. The methodology is further illustrated using survival data from patients with squamous cell carcinoma of the oropharynx, highlighting its practical relevance in biomedical survival analysis. The proposed method offers a flexible, interpretable, and computationally simple framework for nonparametric inference with structured lifetime data under weak stochastic ordering information. Full article

The occurrence of pesticide residues in pome fruits and their implications for consumer health remain critical concerns in food safety. In this study, 222 pesticide residues were analysed in 155 samples of apples, pears, and quinces collected from Türkiye between October 2025 and March 2026 using liquid chromatography–tandem mass spectrometry (LC-MS/MS). Residues were detected in 76.4% of apples, 86% of pears, and 30% of quinces, with frequent multi-residue patterns and notable occurrences of non-approved compounds. Pear samples exhibited the highest contamination levels, with maximum residue level (MRL) exceedance rates reaching 30%, compared to 14.5% in apples and 2% in quinces. Quality assessment based on the index of quality for residues (IqR) indicated that 96% of quince samples were classified as excellent or good, demonstrating the most favourable profile among the evaluated commodities. Risk ranking analysis further indicated that acetamiprid was the only high-risk pesticide in apples, whereas residues in pears were predominantly medium risk, and all detected compounds in quinces fell within the low-risk category. Deterministic risk assessment indicated that chronic exposure remained well below levels of concern for both adults and children. Under combined pome fruit consumption, acetamiprid and spirodiclofen were identified as the main contributors to chronic hazard index (HIc), accounting for 33% and 13% of HIc, respectively. However, acute exposure exceeded the safety threshold (HQa > 1) in children for acetamiprid in both apples and pears. Probabilistic modelling confirmed right-skewed exposure distributions and highlighted increased risk under cumulative consumption scenarios. Full article

The ‘molecular mimicry theory’ states that foreign antigens introduced during infection can activate autoreactive T or B cells, leading to autoimmune diseases. However, despite a decrease in infectious burden, autoimmune disease incidence is on the rise globally. To address this paradox, we analyzed the impact of benzo[a]pyrene (BaP) on the autoimmune-prone mouse strain MRL. We found that BaP induced the expression of genes, the protein products of which showed homology to bacterial pathogens, in the MRL spleen and kidneys. Based on our findings, we propose the hypothesis that environmental pollutants may ‘mimic’ the impact of pathogen invasion on the immune system in autoimmune-susceptible individuals. Full article

Ampicillin residues in animal-derived foods may cause allergic reactions and promote antimicrobial resistance in consumers; however, data on residue behavior in poultry remain limited. This study aimed to evaluate the depletion of ampicillin in muscle and skin plus fat of broiler chickens. Thirty birds were treated with ampicillin intramuscularly (20 mg kg⁻¹ every 24 h for three days) and sacrificed at 0.5, 1, 2, 5, and 9 days post-administration. Samples were analyzed by liquid chromatography coupled with tandem mass spectrometry, a method successfully validated according to Commission Implementing Regulation (EU) 2021/808, VICH GL49 and GL2. Quantification was performed by linear regression from matrix-matched calibration curves. Residue depletion was evaluated following the European Medicines Agency guidelines. Ampicillin residues in muscle were detected only during the first 24 h post-administration (6.50–8.48 µg kg⁻¹). Residues in skin plus fat remained detectable until day 5 post-administration (6.87–59.88 µg kg⁻¹). Based on this, the withdrawal period calculated for skin plus fat was 9 days considering EU maximum residue limit (MRL) and 19 days considering method limit of quantification, with 95% confidence. These results provide critical data on ampicillin residue kinetics under controlled experimental conditions, supporting risk assessments and the establishment of MRLs in broiler chickens by the Codex Alimentarius. Full article

Pesticides play a crucial role in modern agriculture by protecting crops from pests, diseases, and weeds, thereby contributing to increased agricultural productivity and food security. However, their extensive use may lead to the presence of residues in food products, particularly vegetables, which can pose potential risks to human health. Therefore, continuous monitoring of pesticide residues in vegetables is essential to ensure food safety, assess dietary exposure, and protect consumers from possible acute and chronic health effects associated with pesticide intake. In this study, the concentrations of pesticide residues were determined in 1236 samples of 44 vegetable species collected over a four-year period. Vegetables originated from 39 countries, including Serbia (n = 213). Pesticide residues were determined by liquid chromatography–tandem mass spectrometry (LC-MS/MS) and gas chromatography–tandem mass spectrometry (GC-MS/MS) after extraction using a modified QuEChERS protocol. A total of 148 pesticide residues were detected. Of the vegetable samples, 40.13% had pesticide residues at or above 0.01 mg/kg, and 1.78% exceeded the maximum residue limits (MRLs) set by the Serbian regulation. MRL values were most often exceeded in ginger, cucumber, and spinach. The most frequently found pesticide was imidacloprid (detected in 74 samples, 5.99%). Multiple pesticides were detected in 22.01% of the vegetable samples, and one tomato sample contained up to 10 pesticide residues. Based on the available data and further development of a representative dataset, together with appropriate statistical analyses, dietary exposure assessments for pesticides can be conducted. Full article

South Korea is a highly import-dependent food economy and therefore offers a useful case for examining how an integrated national food control system can be built under trade openness, limited domestic agricultural capacity and changing consumer risk perceptions. This article presents a structured narrative review, rather than a causal impact evaluation, of South Korea’s transition from multi-agency food safety regulation toward an integrated, risk-based food control system. The review is organized through the FAO/WHO national food control system framework and maps Korean legal, institutional and operational evidence onto six analytical dimensions: legal foundations, institutional coordination, risk-based official controls, import supervision, traceability and recall, and risk communication. Examples of embedded risk-analysis principles include the Positive List System for pesticide residues with a default limit of 0.01 mg/kg for substances without a Korean MRL, inspection orders and risk-ranked import controls, barcode-linked recall blocking through the Hazardous Food Sales Prevention System, and public disclosure of unsafe directly purchased overseas products. Quantitative evidence is used descriptively: Korea’s agricultural and food imports reached USD 45.3 billion in 2024, hepatitis A notifications fell from 17,598 in 2019 to 3989 in 2020 after the salted-clam outbreak, and MFDS reported that 12 of 544 overseas direct-purchase products tested in the first half of 2020 contained restricted substances. These indicators suggest improvements in coordination and crisis response capacity, but they do not prove that institutional integration alone reduced foodborne disease incidence. The review finds that South Korea’s model is strongest in institutional consolidation, import-oriented technical standards and digital recall communication, while key challenges remain in small-business compliance burden, scientific independence, data transparency, cross-border e-commerce and novel foods such as cell-cultured food ingredients. Full article

Background: Interpretation of pesticide residues in fruits requires tight integration of surveillance evidence, analytical capability, regulatory context, and mitigation data. Methods: This critical integrative review synthesises analytical chemistry, cumulative risk assessment (CRA), regulatory divergence, and mitigation evidence, strengthened by quantitative monitoring summaries and auditable regulatory examples. Routine enforcement continues to rely on validated QuEChERS extraction coupled with targeted LC-MS/MS and GC-MS/MS. High-resolution mass spectrometry (HRMS) adds unique value for metabolites, transformation products (TPs), and incident response, but its routine enforcement role remains constrained by confirmation logic and harmonised validation. Results: Monitoring shows that exposure is typically multi-residue rather than single-compound; the key interpretive challenge therefore shifts toward CRA prioritisation, sensitive-subpopulation assumptions, and transparent distinction between compliance signals and toxicological inference. We provide (i) headline compliance metrics from EU and US programmes, (ii) surveillance-derived high-frequency residue patterns and co-occurrence motifs to guide CRA prioritisation, (iii) an illustrative, traceable comparison of EU/US/Codex MRL divergence for emblematic citrus residues with EU evidence extracts and US/Codex traceability records, and (iv) mitigation evidence statements standardised by study type and transformation-product reporting. Conclusions: Pesticide residues in fruits should be interpreted through a risk-based framework that distinguishes compliance findings from toxicological concern, prioritises relevant multi-residue drivers, and evaluates mitigation according to both residue reduction and transformation-product uncertainty. Full article

Ethylene oxide (EtO) has been banned in the European Union since 1991 as a fumigant for food commodities. Nevertheless, recurrent contamination incidents, especially since 2020, involving imports from India, have raised significant food safety concerns. Despite regulatory measures, EtO and its metabolite, 2-chloroethanol (2-CE), continue to be detected in a variety of food products, including dried foods, dietary supplements, and food additives. This study presents a QuEChERS-based method involving the conversion of EtO into 2-CE, which is subsequently quantified by isotope dilution gas chromatography–tandem mass spectrometry (GC-MS/MS). In contrast to previously published methods, this protocol utilises an Agilent HP-5ms Ultra Inert column (30 m × 250 μm × 0.25 mm), routinely employed in our laboratory for multi-residue pesticide analysis. The proposed approach is therefore readily adaptable to laboratories already performing multi-residue analyses, as it does not require modifications to existing instrumental configurations. The method was validated in accordance with SANTE/11312/2021 guidelines. A total of 84 samples, primarily imported from India, as well as from Brazil, Argentina, and the United Kingdom, were analysed. 2-CE was detected in four samples, and in two cases, the sum of EtO and 2-CE, expressed as EtO, exceeded the European Union (EU) maximum residue limit (MRL). Full article

Metagenomics analysis is a critical tool in identifying and typing viral samples to aid surveillance, clinical, epidemiological, and other workflows. Despite advances in sequencing technology and analysis pipelines, there are still limitations that lead to reduced taxonomic resolution or false positives from highly recombinant or challenging samples. Here we describe MGtree, a novel metagenomics pipeline that utilizes a combination of full-length read alignments and phylogenetic analysis to classify samples of interest. We demonstrate that MGtree accurately genotypes viral samples from challenging norovirus and HPV datasets. MGtree outperforms the popular metagenomics programs Kraken2 and Centrifuge, and it succeeds with low-input samples where de novo assembly fails. MGtree’s correct assignments across highly mutant and coinfected samples highlights its ability to resolve viral genotypes and its potential to improve classification precision in complex samples. Full article

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by immune dysregulation and multi-organ damage. Abnormal B cell activation and autoantibody production constitute the core pathological mechanism of SLE. However, the proportion, BCR pairing types, clonal evolution patterns, and transcriptomic features of dual BCR B cells in SLE remain incompletely elucidated. In this study, we employed single-cell RNA sequencing (scRNA-seq) combined with single-cell B cell receptor repertoire sequencing (scBCR-seq) to preliminarily analyze the proportion and characteristics of dual BCR B cells in SLE model mice (MRL/Lpr and SLE.Yaa) as well as in peripheral blood from SLE patients. The results showed: (1) Compared with control groups, the proportion of dual BCR B cells in SLE model mice and patients exhibited a decreasing trend, whereas the diversity of the CDR3 repertoire decreased and clonality increased. Increased clonal sharing was observed between single BCR B cells and dual BCR B cells. The main pairing types of dual BCR B cells were H + κ1 + κ2, H1 + H2 + κ, and H1 + H2 + κ + λ, with preferential utilization of autoimmunity-associated V gene families such as IGHV4-34, and high expression of IGHG subtypes. (2) Tracking analysis of B cell receptor clonality and effector molecule expression revealed that in SLE, dual BCR B cells tend to enrich in IFN-α/γ responses, TNF-NFκB inflammation, and complement pathways, and highly express interferon-related genes such as Ly6a, Isg15, MX1, and IFI6. (3) In both single BCR B and dual BCR B cells from SLE patients, the proportion of the naïve B cell subset decreased, whereas the proportions of plasma and Breg subsets increased and exhibited clonal expansion. SLE dual BCR Breg cells highly expressed IL10, HSPA1A, and others. This study is the first to reveal, at the high-throughput single-B-cell level, that the proportion, subset origin distribution, CDR3 repertoire composition, and effector molecule expression of dual BCR B cells display unique characteristics in SLE model mice and patients, providing baseline comparative data and novel research perspectives for further investigation into B cell effector functions and mechanisms in SLE patients. Full article

Background: Current murine glioblastoma (GBM) models do not incorporate tumor resection and thus do not allow study of recurrent GBM after surgery, including postsurgical changes in the tumor microenvironment (TME), thereby limiting translational relevance. Methods: In phase 1 of a three-phase study, we compared tumor cell implantation into a cavity created using conventional microdissection techniques or the Myriad Research Laboratory System (MRLS) versus direct implantation into the brain without a cavity, and assessed morbidity using the neurological severity score (NSS). In phase 2, we developed a new surgical resection model, the Surgical murine GBM resection model (Sur-rGBM), and examined the effects of tumor resection on the tumor microenvironment (TME) and on overall survival. In phase 3, we compared the therapeutic response to temozolomide (TMZ) with or without anti-VEGF antibody, after resection (Sur-rGBM) or no resection. Tumor growth was confirmed before and after resection by ultrasound. Animals were euthanized for immunohistochemical assessment at maximal tumor growth. Results: Creating a cavity for tumor cell implantation using MRLS improved survival compared to direct cell injection with no cavity. Tumor resection increased survival, and TMZ combined with an anti-VEGF antibody after tumor resection improved survival compared with surgery or TMZ alone. Resection induced significant changes in biomarker expression within the TME. Conclusions: Our novel murine GBM surgical resection model (Sur-rGBM) provides reliable, controlled tumor growth and a standardized resection technique to facilitate studies on TME changes and therapeutic response after tumor resection. Full article

Vegetables constitute an essential component of the daily diet in Albania; however, they also represent a major pathway of human exposure to pesticide residues. This study investigates the presence of pesticide residues in widely used vegetables, including leafy, fruity, root, and bulb types, and evaluates the potential dietary health risks associated with their consumption. Vegetable samples were analyzed using gas chromatography–tandem mass spectrometry (GC-MS/MS) and liquid chromatography–tandem mass spectrometry (LC-MS/MS), for the presence of 417 pesticide analytes, ensuring high analytical sensitivity and reliability. Pesticide residues were present, with 42 distinct compounds, including metabolites, found in all the analyzed samples. Notably, some of the detected substances are not currently authorized for use as plant protection products, suggesting either environmental persistence or regulatory non-compliance. Exceedances of European Union maximum residue limits (MRLs) were most frequently detected in leafy vegetables (42.31%), followed by fruity vegetables (18.75%), whereas no MRL exceedances were observed in root and bulb vegetables. According to the dietary exposure assessment conducted using European Food Safety Authority Pesticide Residue Intake Model (EFSA PRIMo model v.3.1), chronic dietary exposure to pesticide residues was below the acceptable daily intake (ADI). According to this assessment, the acute exposure exceeded the acute reference dose (ARfD) for several pesticide–vegetable combinations, particularly among children. This highlights the need for ongoing monitoring and better agricultural management techniques to reduce potential health risks related to pesticide residues in vegetables. The study results indicate the need to strengthen national monitoring programs, enforce pesticide regulations more strictly, and promote the wider adoption of integrated pest management strategies to reduce dietary pesticide exposure and protect public health in Albania. Full article

Dietary supplements, especially lycopene-containing ones, are of interest because of their antioxidant and potential health-promoting effects; however, their actual composition and safety have not been sufficiently verified. This study evaluated the accuracy of labelled lycopene content and assessed selected chemical and microbiological safety parameters in commercially available products. Lycopene levels were determined spectrophotometrically and by HPLC, whereas pesticide residues, heavy metals, and microbiological purity were analysed using validated regulatory-compliant methods. Marked inconsistencies were found between the declared and measured lycopene content, with HPLC revealing concentrations up to 70% above label claims. Methomyl (0.059 mg/kg), a pesticide not approved in the EU, was detected in one supplement, heavy metal concentrations met current regulatory limits, and other elements remained below quantification thresholds. Microbiological quality was satisfactory, with low total viable counts and absence of pathogens, yeasts, and moulds; only low levels of environmental spore-forming bacteria were detected. The findings highlight acceptable microbiological and elemental safety but reveal substantial deviations in lycopene content labelled/determined and the presence of a non-approved pesticide (however, below the MRL). A comprehensive multi-parameter quality assessment is essential to ensure the safety, reliability, and regulatory compliance of lycopene supplements. Full article

This study presents a novel approach for optimizing GC-MS/MS performance and ensuring the reproducibility of pesticide residue analysis across diverse food matrices. Analysis of thermally treated (100–280 °C) extracts using GC-MS (scan mode) and FTIR revealed that strawberry and dry mint contain significantly higher concentrations of non-volatile co-extractives of varying chemical natures compared to fennel seeds. It was further elucidated that polar non-volatile co-extractives exhibit a more pronounced negative impact on analytical performance. Consequently, a synergistic approach was developed for strawberry analysis, combining end-column back-flushing with the application of fennel extract as a Natural Analyte Protectant (NAP). For dry mint, optimal results were achieved through a different approach: standard forward carrier gas cleaning combined with a fivefold sample dilution. The developed protocols enabled the efficient analysis of 195 pesticides in strawberries, all achieving LOQs of 0.01 mg/kg. Results demonstrated high precision (RSD < 3% for most analytes) and excellent recoveries (90–110%) at 0.01 and 0.05 mg/kg. Furthermore, 154 and 186 pesticides were successfully validated in dry mint with LOQs of 0.01 and 0.05 mg/kg, respectively. This research demonstrates that efficient column cleaning can be achieved through either back-flushing or the same forward-flow of the carrier gas, depending on whether the non-volatile co-extractives are polar or non-polar. Finally, ethyl acetate (EtOAc) fennel extract is introduced as a highly effective NAP, which is especially advantageous for samples lacking endogenous volatile components while simultaneously containing high concentrations of polar co-extractives. Pesticide residue monitoring was applied for 20 commercial samples, demonstrating high sensitivity. While strawberry samples exhibited excellent regulatory compliance and a total absence of chlorpyrifos, herbal matrices showed a higher chemical burden characterized by multi-residue co-occurrence and MRL exceedances. Full article

Antimicrobial resistance (AMR) is increasingly becoming a major global public health concern, as antibiotics are losing their effectiveness at an alarming rate due to drug resistance. The ß-lactam group of antibiotics are widely used in dairy farms to treat animal infections, and their presence in the food chain is a significant concern. Addressing this issue requires the development of effective analytical tools for the rapid detection of antibiotics. In this work, a miniaturized Biosensor-on-Pillar platform was developed for detecting ß-lactam antibiotics in milk, which operates in a rapid, cost-effective, and user-friendly format, making it particularly suitable for resource-limited settings. The platform employs an enzyme induction-based approach, wherein Bacillus cereus spores germinate in the presence of β-lactam antibiotics, leading to the production of β-lactamase enzyme, which is then recognized using a chromogenic substrate functionalized on paper associated with the pillar platform. The developed biosensor can detect 12 β-lactam antibiotics with limits of detection (LODs) ranging from 1 to 1000 ppb, achieving sensitivity at or below the maximum residue limits (MRLs) set by regulatory bodies (FSSAI/CODEX) for the majority of the tested antibiotics. The performance of the platform, including the design, fabrication, and working principle, was further evaluated by analyzing six blind milk samples, yielding significant results compared to the commercially available AOAC-approved gold-standard method. Hence, the developed biosensor demonstrates promising potential for the rapid, cost-effective and high-throughput screening of milk samples for β-lactam antibiotics, benefiting the dairy industry and ensuring food safety. Full article