Acceptance Criteria Research Articles

Development and optimization of a high-throughput LC-MS/MS method for the simultaneous determination of Exatecan and its Cathepsin B-sensitive prodrug, and ARV-825 in rat plasma: Application to pharmacokinetic study.

Development and optimization of a high-throughput LC-MS/MS method for the simultaneous determination of Exatecan and its Cathepsin B-sensitive prodrug, and ARV-825 in rat plasma: Application to pharmacokinetic study.

Deep learning-based image classification and quantification models for tablet sticking.

Deep learning-based image classification and quantification models for tablet sticking.

Analytical validation and clinical performance of a plasma-based CGP assay, NEO | PanTracer LBx.

e15047 Background: Comprehensive genomic profiling (CGP) assays targeting hundreds of genes are increasingly used over smaller panels in patients with advanced solid tumors. CGP by liquid biopsy (LBx) complements traditional tissue-based CGP, mitigating tissue constraints, heterogeneity, and wait times. Here we describe the analytical validation (AV) and clinical performance characteristics of NEO | PanTracer LBx. As part of the clinical validation (CV), we report initial results across advanced stage cancers and compare concordance with an in-house amplicon-based 37-gene lung cancer panel (InVisionFirst-Lung) and other LBx CGP assays. Methods: Based on TSO500 chemistry, PanTracer LBx is a pan-solid tumor, next-generation sequencing assay designed to detect single nucleotide variants (SNVs) and small insertions/deletions (Indels), copy number variants (CNV), and fusions across, 517, 59 and 23 genes, respectively, as well as blood tumor mutational burden (bTMB) and microsatellite instability (MSI). Key assay performance characteristics (Limit of Detection, LoD; Limit of Blank, LoB; precision, analytical sensitivity/specificity) were determined for the above alteration types. Clinical validation is underway, testing specimens from patients with advanced cancers, from the same timepoint, with PanTracer LBx and InVisionFirst-Lung (n = 145 pts) or commercially available pan-tumor LBx CGP assays (n = 57 pts). Initial comparisons were limited to pathogenic variants in genomic regions with mutual coverage. Results: LoD90 assessment utilized SeraSeq complete ctDNA reference material at different input concentrations to detect known somatic variants present at different %VAF levels (0.1%-2%). LoD90 was estimated to be 0.17% for SNVs, 0.31% for Indels, 0.5% for fusions and 1.23x for CNVs. LoB for SNVs, Indels, CNVs and fusions, assessed by calculating the cumulative per gene specificity across 21 healthy donors tested, was 0%. To assess the analytical sensitivity and specificity, patient samples were sequenced and compared to results obtained with InVisionFirst -Lung. Positive percent agreement (analytical sensitivity) and negative percent agreement (analytical specificity) were 96.9% and 99.3%, respectively. Precision (inter-assay, -lot and -operator) was > 95%. CV confirmed high concordance rates between PanTracer LBx and LBx CGP assays with 92% agreement (47/51 variants). Conclusions: Performance evaluation of PanTracer LBx met all pre-specified AV acceptance criteria. Leveraging a large panel targeting key classes of somatic alterations across multiple genes, PanTracer LBx demonstrates results consistent with a smaller, highly sensitive targeted panel and similar large CGP panels. Additional CV is ongoing; further analysis will include additional samples, tumor-specific findings, cross-test comparisons, and particular biomarker and immune signature findings (MSI and bTMB).

Assessment of the performance of a dual-sample oral cholate challenge test: The HepQuant DuO test.

Assessment of the performance of a dual-sample oral cholate challenge test: The HepQuant DuO test.

Quantification of 3‑chloro-7‑hydroxy-4-methylcoumarin (CHMC) in urine as a biomarker of coumaphos exposure by high-performance liquid chromatography-fluorescence detection (HPLC-FLD).

Quantification of 3‑chloro-7‑hydroxy-4-methylcoumarin (CHMC) in urine as a biomarker of coumaphos exposure by high-performance liquid chromatography-fluorescence detection (HPLC-FLD).

Development and Method Validation for the Quantitative Estimation of Diclofenac Sodium Tablet by Spectrophotometric Method

Abstract: Spectrophotometric method is used to developed and validated for quantifying and detecting the drug diclofenac sodium. The analytical process development and validation are essential for finding the easiest way to evaluate diclofenac sodium with maintain the safety, quality and effectiveness of pharmaceutical products. Ultra Violet (UV) spectroscopy is commonly used for substance analysis in the pharmaceutical industry due to its ability to deliver quick and accurate results. The technique measures the absorption of the ultra violet light, typically between 200-400 nm, making it effective for analyzing compounds based on their UV absorption characteristics. To meet regulatory requirements, the method must be validated for parameters such as specificity, precision, accuracy, reproducibility, limit of determination (LOD), and limit of quantification (LOQ) This ensures that the technique provides reliable and consistent measurements of active pharmaceutical ingredients and excipients, following established guidelines for optimal performance and quality control. This method follows the BeerLambert's Law. Accuracy of the drug was about the acceptance criteria as per the ICH guidelines.48

Polycyclic Aromatic Hydrocarbons (PAHs) in Household Dusts: Distribution, Sources, and Health Risk Assessment from Rural Areas in Chiang Mai Province, Thailand

The present study investigated the concentrations, sources, and potential health risk assessment of polycyclic aromatic hydrocarbons (PAHs) in house dust from residences in Samoeng District, Chiang Mai Province, Thailand. Samples of house dust from 48 households were analyzed for 16 PAHs. The total concentrations of PAHs (ΣPAHs) ranged between 270.1 to 45,386.8 ng g−1, with a mean of 3942.4 ± 8175.1 ng g−1. Pyrene (Pyr), benzo(k)fluoranthene (BkF), and indeno(1,2,3-cd)pyrene (IcdP) were the predominant compounds. Diagnostic ratios and principal component analysis (PCA) showed wood and the burning of biomass as the predominant sources. Evaluations of incremental lifetime cancer risk (ILCR) showed higher risks, especially for children (average ILCR = 6.57 × 10−3), with dermal contact as the main exposed pathway. Risks exceeded acceptable criteria (10−6 to 10−4), suggesting serious public health problems. The results highlight the significance of pollution mitigation measures, such as reducing the use of biomass combustion and improving indoor air quality, for protecting vulnerable populations in rural regions. The research conducted presents important insights into the environmental health impacts of PAHs in residences and shows the importance of public health procedures that can reduce exposure.

Stabilization of Abiraterone in Human Plasma Using the Esterase Inhibitor Bis(4-nitrophenyl) Phosphate: A Short Communication.

Abiraterone, an active metabolite of abiraterone acetate, is used for the treatment of prostate cancer. Therapeutic drug monitoring (TDM) of abiraterone could improve treatment outcomes. However, its stability in plasma for only 4 hours at room temperature, is making the TDM implementation difficult in clinical practice. Stabilization experiments were performed in our laboratory using esterase inhibitors for the stabilization of abiraterone acetate in preclinical samples. The esterase inhibitor bis(4-nitrophenyl) phosphate (BNPP) stabilizes abiraterone acetate and abiraterone as well. Therefore, we investigated whether the esterase inhibitor BNPP could stabilize abiraterone in fresh human plasma. BNPP at 1 and 10 mM were evaluated for its stabilizing effects on abiraterone in fresh human K2EDTA plasma. The samples were analyzed using a validated liquid chromatography-mass spectrometry (LC-MS/MS) method. A partial validation assessed BNPP's impact on accuracy, precision, selectivity, and specificity within the fully validated LC-MS/MS method. BNPP at 10 mM, but not 1 mM, effectively prevented abiraterone degradation in fresh human K2EDTA plasma, maintaining stability for at least 5 days at room temperature. Partial validation confirmed that all results met the acceptance criteria of the European Medicines Agency guidelines and the US Food and Drug Administration guidance. We demonstrated that the esterase inhibitor BNPP effectively stabilizes abiraterone in fresh human K2EDTA plasma. BNPP had no significant effect on the accuracy, precision, selectivity, or specificity of LC-MS/MS for abiraterone detection. The addition of BNPP to clinical abiraterone samples may be helpful in implementing abiraterone TDM in daily clinical practice.

Assessing Creep–Fatigue Interactions in Wrought and LP-DED-Processed 316 Stainless Steel

Abstract This study examines the low-cycle fatigue (LCF) and creep–fatigue (CF) behavior of wrought 316L and 316H stainless steels to develop acceptance criteria for accelerated testing of additively manufactured (AM) stainless steels. New LCF and CF data were generated between 550 and 700 °C, focusing on the impact of temperature, control mode, and hold time on fatigue life. Life assessment methods, including time fraction (TF), ductility exhaustion (DE), and stress-modified DE (SMDE), were evaluated for their applicability to nuclear code cases. Results highlight that conventional accelerated CF tests often lead to fatigue-dominated failures due to insufficient hold times. DE and SMDE models correlated more effectively with experimental data than TF, particularly when non-damaging viscous strains were excluded. Testing laser powder-directed energy deposition (LP-DED) 316H revealed non-conservative life predictions across all models, contrasting with the conservative predictions for wrought 316L and 316H, despite comparable LCF and creep properties. These findings underscore the need to refine accelerated CF test protocols to better capture damage mechanisms in AM materials.

Bioburden of postmortem bone tissues with a procurement time exceeding 36 h

To qualify for bone donation many criteria must be met. For procurement, two time intervals—a postmortem interval (PMI) of 6 h (hours) until cooling of the deceased and a maximum procurement time of tissues within 24/36 h postmortem are mandatory. Expanding the procurement to donors with a longer PMI would be helpful e.g. to have more time to contact relatives for consent for donation. A loss of biomechanical quality of bone tissues should not be expected in the PMI until procurement, but the question of microbiological contamination remains. Therefore, samples from the iliac crest were procured under standard procurement conditions between 48 and 54 h (n = 14, group 1) and 72–78 h (n = 7, group 2) postmortem (pm). Samples were immediately frozen after procurement at < − 18 °C and sent to the German Institute for Tissue and Cell Replacement (DIZG) for mechanical preparation. Additionally, chloroform treatment was performed at the tissue bank of the Charité Berlin. After each step the samples were refrozen and sent to a contracted microbiological lab for bioburden testing according to the European Pharmacopoeia. Samples were tested after procurement, preparation, and chloroform treatment respectively. As acceptance criterion a maximum amount of 9 × 104 colony forming units per gram (CFU/g) tissue was defined. All samples were within the defined limit with a maximum value of 2.5 × 102 CFU/g. These values are in the range of bone tissues procured under non-strict-aseptic procurement conditions within 24 or 36 h and are within the capacity of the peracetic acid sterilization process used by several tissue banks.

Assessing linearity of vaccine immunogenicity assays: application and link with clinical endpoints.

Assessing the performance of an immunogenicity assay before using it to support vaccine clinical trials is mandatory. Further validation of assay performance is even requested to support Phase III studies. While assay validation requires adherence to predefined acceptance criteria, there is no universal stringency level for earlier phases of assay development. Setting scientifically sound criteria for success is about finding the right balance between unavoidable assay limitations and ensuring the assay is fit-for-purpose. In this paper, we focus on the evaluation of linearity for immunogenicity assays and its use as surrogate for accuracy evaluation in the absence of reference material. We propose a simple method for evaluating assay linearity and understanding the impact of a linearity deviation on the evaluation of the response increase in clinical trial. Assessment is reliable in absence of known concentration samples, unlike methods in industry guidance, making the proposed method more versatile. Method is illustrated by two case studies, representative of the assays used in the vaccine field. Making the link between assay linearity and clinical endpoints provides a simple and clear framework to support the definition of assay validation criteria, applicable to a variety of immunogenicity assays.

Seismic Performance of Chevron-Braced Steel Buildings with Beam Yielding Mechanism Using FEMA P695 Methodology

Current seismic design provisions for chevron-braced frames require that the chevron beams resist the unbalanced force due to simultaneous brace buckling and tensile yielding, leading to deep heavy chevron beams. Results of large-scale chevron braced frames have demonstrated that allowing limited chevron beam yielding reduces this unbalanced force and is not detrimental to the lateral resistance of chevron-braced buildings. This proposed design reduces the size of beams in chevron-braced frames. This study evaluates the seismic performance of 3-story and 9-story prototype buildings with the proposed design. The novelty of this research lies in applying FEMA P695 seismic provisions for performance and collapse risk assessment, and ASCE 41 modeling parameters and acceptance criteria for nonlinear brace, beam, and column elements in the numerical building models. Results indicate compelling evidence that the proposed design with reduced sized chevron beams offer seismic performance comparable to frames designed according to current AISC provisions. The collapse risk in 50 years remains within acceptable limit of 2% for both designs. Additionally, the proposed design also provides a more economical solution, reducing structural weight of the braced-frame by up to 8%, thus enhancing the applicability in practice for chevron-braced steel buildings.

Reliability and usability of a portable spirometer compared to a laboratory spirometer

BackgroundAccess to spirometry remains limited due to the expense and inconvenience of stationary laboratory spirometers, which may compromise the diagnosis and management of chronic respiratory diseases (CRDs), such as chronic obstructive pulmonary disease (COPD) and asthma. Portable spirometers offer potential advantages over laboratory spirometers in terms of affordability, user-friendliness, and portability. The objective of this study is to evaluate the reliability and usability of a portable spirometer (Medcaptain VC-30 Pro) compared to a conventional laboratory spirometer (Jaeger MasterScreen PFT).MethodsIn this multi-center, randomized, open-label crossover study, 132 subjects from two hospitals were recruited to perform pulmonary function tests using both the portable spirometer and the laboratory spirometer. Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, peak expiratory flow (PEF), forced expiratory flow between 25 and 75% of FVC (FEF25-75%), vital capacity (VC), maximal voluntary ventilation (MVV), and forced expiratory volume in six seconds (FEV6) were compared for correlation and agreement between two spirometers. The concordance of their spirometric abnormality diagnoses and severity classifications was assessed. An additional 30 healthy volunteers were recruited to perform a pulmonary function test by themselves after a session guided by specialists to evaluate the usability of the portable spirometer.ResultsA total of 126 recruited participants achieved acceptable pulmonary function test results. The intraclass correlation coefficients (ICCs) for primary outcomes FEV1 and FVC were 0.994 and 0.993, respectively (both p < 0.001). ICCs for other outcomes ranged from 0.968 to 0.995 (all p < 0.001). The Bland–Altman analysis showed that FEV1 and FVC met preset acceptable criteria, with 96.0% of values falling within the 95% limits of agreement (LoA). Cohen’s kappa statistics for the diagnosis of spirometric abnormality and classification of severity were 0.872 and 0.878, respectively. In the usability test, 28 out of 30 volunteers obtained a Grade A result.ConclusionsThe portable spirometer exhibited a strong correlation and agreement with a high-quality laboratory spirometer, as well as concordance in spirometric abnormality diagnosis and severity classification. Non-specialist can obtain acceptable results using this portable spirometer.

"Pero like, you don't speak Spanish?" exploring the role of language fluency on Latine intragroup identity denial, likability, and befriending.

Anecdotal narratives and recent qualitative studies demonstrate that in Latine communities, language proficiency can be a form of gatekeeping (i.e., determining the legitimacy of people's claims to a particular status by unilaterally imposing criteria for acceptance) Latinidad. Latine individuals who are not fluent in Spanish frequently report having their Hispanic/Latine identity questioned and denied. Across two experiments, we investigated whether Latine individuals perceive non-Spanish-speaking Latine individuals as identifying less with their Latine identity. Across two studies, Latine adults (N = 302, Mage = 35.21, SDage = 10.83) were randomly assigned to view one of two Latine individuals' social networking profiles (i.e., fluent in English or fluent in both English and Spanish). Afterward, they reported their perceptions of the targets' perceived ethnic identity, likability, and likelihood that they would befriend the target. Latines, regardless of how strongly they identified as Latine, or if they themselves were bilingual (Study 2), perceived a Latine person only fluent in English as being less likely to identify as Latine and were less likely to want to befriend them (Study 1) compared to a Latine target fluent in both English and Spanish. Latine perceivers use language fluency to challenge the identity of their non-Spanish-speaking Latine counterparts and, in some cases, to make judgments about potential friendship. These findings extend previous research on identity denial and intragroup dynamics by advancing our understanding of the relationship between language fluency, identity denial, and other forms of intragroup rejection within the Latine community. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

Chronic toxicity of the UV filter Octocrylene to the sea urchin, Arbacia punctulata.

With increasing concern over the environmental safety of cosmetic and personal care product (CPCP) ingredients discharged to the aquatic environment, a need to evaluate the risk of recreational ultraviolet filter (UVF) emissions in coastal marine environments has grown in prominence. A commonly used UVF, octocrylene (OC), has been detected in several monitoring studies of coastal environments, emphasizing the need for a marine environmental safety assessment. A review of the literature identified that there is a paucity of reliable marine chronic toxicity data available to generate toxicological thresholds for OC. While leveraging freshwater data is possible, this results in the incorporation of significant uncertainty in the assessment as key marine taxa (such as echinoderms, mollusks, or cnidarians) cannot be suitably represented. To help remedy this, United States Environmental Protection Agency Test Method 1008.0 (Sea urchin, Arbacia punctulata, Fertilization Test) was conducted to evaluate the chronic toxicity of OC on sea urchins. All test acceptability criteria were met, and concentrations of OC were adequately maintained in the test system. The resultant fertilization EC10 was 41.5 µg/L, indicating that A. punctulata fertilization is less sensitive to OC exposure than freshwater invertebrate reproduction results to date. This data point serves to further the octocrylene marine chronic ecotoxicological profile, but ultimately more data are needed prior to conducting a robust environmental safety assessment.

Extension of an Ultra-High Performance Liquid Chromatography–MS/MS Method for the Determination of C3 Epimers of 25-Hydroxyl Derivatives of Vitamin D in Human Plasma

Abstract Current vitamin D quantification methods do not account for 25-hydroxyl epimers, which can falsely increase concentrations and mask actual deficiencies. Previously, we developed an ultra-high performance liquid chromatography–tandem mass spectrometry method to measure 25(OH)D3, 3-epi-25(OH)D3 and 25(OH)D2; here, we extended this method to include 3-epi-25(OH)D2. Analytes were separated using a Shimadzu UPLC with a Kinetex F5 column (100 × 2.1 mm, 2.6 μm). The mobile phase contained 0.1% formic acid in methanol and water (70:30, v/v). The internal standard, deuterated 25(OH)D3 and analytes were extracted with hexane. Detection was performed by a mass spectrometer equipped with a triple quadrupole after prior electrospray ionization. It demonstrated sufficient precision and spike recovery within and between days, with a coefficient of variation ≤15% and an error of determination ≤18%. The method exhibited linearity in the 2–100-ng/mL concentration range. The limits of quantification and limits of detection were 2 and 1 ng/mL, respectively. Extraction recoveries ranged from 70.05% to 97.13%. The matrix effect, carryover and dilution integrity were evaluated and met the FDA acceptance criteria. The stability of all metabolites in plasma was confirmed after 3 h of storage at room temperature and after three cycles of freezing at −80°C and thawing. Applying the method to clinical samples showed a high 25-hydroxyl epimer derived from vitamin D.

Medical education research quality (MERSQ) checklist development: Are searches of BEME and non-BEME reviews standard?: A mixed method study.

Even though there has been a lot of research in medical education, the quality of it has not increased similarly. This study aimed to provide a valid and reliable user-friendly tool for evaluating search strategies in medical education systematic reviews. This mixed study was conducted in 2019 to 2021, including 3 phases: systematic search, developing a medical education research quality (MERSQ) checklist, and evaluation of the search quality of best evidence in medical education collaboration (BEME) and non-BEME reviews. Three hundred nineteen items were retrieved from the systematic search of PubMed, Embase, Scopus, Psychinfo, ERIC, and Google Scholar. Following ensuring acceptable criteria, 30 items were included in comprehensiveness or reproducibility guarantees. The results showed that the instrument had an the intra-class correlation coefficient of 0.922 (P = .002), the reproducibility guarantee had 0.903 (P = .003), and the comprehensiveness guarantee had 0.926 (P = .006). We also calculated inter-rater reliability and internal consistency using Cronbach alpha of 0.827 (P < .001) and an instrument the intra-class correlation coefficient of 0.978. Using MERSQ, the overall search quality (41.75 vs 31.25, P = .009), reproducibility (22 vs 14.50, P = .004), and comprehensive score (18.75 vs 15.75, P = .880) of BEME studies were higher than non-BEME ones. Moreover, we found only 30% of studies completed searching documents. The search strategy query concerning the selection of synonym terms received the lowest score among studies. This study led to the development of a valid and reliable checklist for evaluating the search quality of medical education systematic reviews. Utilizing the MERSQ checklist, we found that BEME studies had higher quality than non-BEME ones, making the results from BEME studies more reliable.

Semi-solid extruded tablets for personalized pediatric use: Development, Quality control and In-Vitro Assessment of Enteral Tube Administration.

Semi-solid extruded tablets for personalized pediatric use: Development, Quality control and In-Vitro Assessment of Enteral Tube Administration.

Validation and clinical performance of a non-commercial ELISA for SARS-CoV-2 anti-RBD IgA antibodies.

Validation and clinical performance of a non-commercial ELISA for SARS-CoV-2 anti-RBD IgA antibodies.

Design and Validation of a Structured Questionnaire Examining the Characteristics, Practice Patterns, and Professional Satisfaction of Yoga Providers in India.

The integration of yoga into modern healthcare systems has highlighted the need to understand the professional landscape of yoga providers in India. Despite extensive research on the benefits of yoga, there remains a significant gap in understanding the characteristics, practice patterns, and professional satisfaction of these providers. The present study aimed to develop a validated questionnaire to address this gap. A structured instrument was developed through an extensive literature review and collation of suggestions from yoga experts. The questionnaire comprised 63 questions across four domains: (1) demographic details, (2) educational background, (3) session specifics, and (4) self-reported professional satisfaction and quality of life. Content validation was conducted with 10 yoga experts using Lawshe's content validity ratio (CVR). Questions with a CVR of ≥ 0.62 were retained. Of the 63 questions, 42 met the acceptance criteria and were included in the final questionnaire. High CVR scores indicated strong relevance and suitability of questions, particularly in sections on session specifics and self-reported assessments, reflecting practical and experiential aspects of yoga practice. The validation process ensured the questionnaire's comprehensiveness and relevance. The validated questionnaire provides a robust tool for assessing the professional landscape of yoga providers in India, facilitating a deeper understanding of their demographics, educational backgrounds, practice details, and professional satisfaction. This tool can guide future research and policy-making aimed at enhancing the quality and effectiveness of yoga practice and instruction in the country.