To determine the proportion of patients achieving target attainment of unbound flucloxacillin in blood plasma, evaluate the association between unbound flucloxacillin concentration and toxicity and identify patient subgroups that may benefit from therapeutic drug monitoring (TDM) of unbound flucloxacillin. A single-centre retrospective observational study was performed of patients admitted to the Meander Medical Centre between 1 July 2023 and 30 June 2024 who were treated with flucloxacillin and had an unbound flucloxacillin concentration measured ≥48 h after initiation of flucloxacillin treatment. Target attainment was defined as an unbound flucloxacillin concentration within 4-10× the measured MIC (0.25 mg/L in the absence of a positive culture). For the first measured plasma sample (n = 203), target attainment was achieved in 33% of patients, 35% fell below the target range and 32% exceeded the target range. Threshold concentrations for unbound flucloxacillin were 10.0 mg/L for nephrotoxicity and 21.0 mg/L for neurotoxicity. Above these concentrations, 66.7% and 46.2% of patients developed nephrotoxicity and neurotoxicity, respectively. An unbound flucloxacillin concentration >10 mg/L was observed in 23 (11.3%) patients, 21 of whom had an glomerular filtration rate <50 mL/min/1.73 m2. Target attainment of unbound flucloxacillin was achieved in one third of patients, while a substantial number of patients had an unbound flucloxacillin concentration >10 mg/L, which was associated with increased toxicity. We advise routine TDM of unbound flucloxacillin for patients with impaired renal function and a high daily dose to mitigate the risk of flucloxacillin-associated nephrotoxicity and neurotoxicity.

High-grade cervical intraepithelial lesions (CIN 2/3) are critical targets for early detection in cervical cancer prevention. MicroRNAs are stable, tissue-specific molecules involved in cancer-related pathways and can be detected in minimally invasive samples, making them suitable for use in the context of liquid biopsies. This exploratory study aimed to identify differentially expressed microRNAs in paired liquid-based cytology (LBC) and plasma samples from women with CIN 2/3, and to evaluate miR-339-3p as a potential biomarker. Samples from 70 women (35 cases with histologically confirmed high-grade lesions and 35 age-matched controls with normal cytology and negative HPV tests) were analyzed using a commercial microRNA panel on the NanoString platform. We identified 57 dysregulated microRNAs in LBC samples and 33 in plasma, with four shared between both matrix types. Among these, miR-339-3p was the only one consistently upregulated and significantly associated with case status. In LBC samples, the area under the curve was 0.65; in plasma, 0.64. Pathway analysis suggested its involvement in apoptosis-related pathways, including PI3K-Akt and p53. Moreover, this study highlights the value of integrating microRNA profiling across local and systemic samples to advance biomarker discovery in cervical cancer.

Due to the lack of relevant detection methods, the existence and function of the intestinal and placental alkaline phosphatase (IAP-PLAP) heterodimer remain largely elusive. Previously, we screened and obtained an aptamer, BG2, which exhibits specific recognition toward the IAP-PLAP heterodimer. Using BG2 as a probe, the heterodimer was found to be highly expressed on the membrane of various tumor cells as well as circulating tumor cells derived from clinical colorectal cancer samples, thus being regarded as a potential tumor marker. However, whether it is shed into extracellular fluid remains unclear. Herein, we developed a BG2-based chemiluminescence assay method with high sensitivity and selectivity for the detection of the IAP-PLAP heterodimer in biological fluids. Furthermore, based on the Na+-dependent binding between BG2 and the IAP-PLAP heterodimer, the captured proteins were successfully released and confirmed indeed IAP-PLAP heterodimer, indicating that they can be shed from the cell membrane into the culture medium. It was also found that the concentration of the IAP-PLAP heterodimer in the cell culture medium is closely correlated with its expression level on the cell membrane. Additionally, the levels of the heterodimer both on the cell membrane and in the culture medium were reduced in senescent cells. These results suggest that the IAP-PLAP heterodimer in body fluids may also serve as a disease marker. We further verified that this method can detect the IAP-PLAP heterodimer spiked in plasma samples with good recoveries, thus providing a method for liquid biopsy.

Pharmacokinetics and efficacy of isometamidium chloride against Trypanosoma vivax in cattle.

Paper-based origami assisted and enhanced electroanalytical detection of β-Amyloid peptide in plasma samples

DIATAGeR: Triacylglycerol annotation of data-independent acquisition based lipidomics.

LC-MS/MS method development and validation for novel targeted anticancer therapies adagrasib, capmatinib, ensartinib, entrectinib, larotrectinib, lorlatinib, pralsetinib, selpercatinib and sotorasib.

Platelet-derived growth factor is increased with cognitive fluctuations and hallucinations in Lewy Body disease.

Several studies have reported detection methods for etomidate and its analogues, metomidate and propoxate, but data on their pharmacokinetics and bioavailability are limited. This study develops a UPLC-MS/MS method to simultaneously detect these compounds and evaluates their pharmacokinetics and bioavailability in mice. Plasma samples were processed using methanol-induced protein precipitation. The separation was conducted on a UPLC BEH C18 column with an acetonitrile-water (containing 0.1% formic acid) as mobile phase at a flow rate of 0.4 mL/min, achieving elution within 4 min. Quantitative analysis was performed using MRM mode coupled with ESI in positive ion mode. In this study, mice received etomidate, metomidate, and propoxate via intravenous (1 mg/kg) and oral (10 mg/kg) routes, and the pharmacokinetics were evaluated. The calibration curves demonstrated excellent linearity within the ranges of 0.5-1000 ng/mL for etomidate, 0.504-1080 ng/mL for metomidate, and 0.77-1540 ng/mL for propoxate in mouse plasma, with correlation coefficients (r values) exceeding 0.998. The developed UPLC-MS/MS method was successfully utilized to analyze the pharmacokinetics of etomidate, metomidate, and propoxate. The absolute bioavailability of etomidate, metomidate, and propoxate was determined to be 14.0%, 21.3%, and 15.3%, respectively.

Sepsis-associated liver dysfunction confounds the association between circulating PCSK9 concentration and mortality in septic patients: A single-center retrospective cohort study.

Extracellular vesicle proteomic expression is influenced by mining tenure in former uranium miners.

Osimertinib, the first-line treatment for nonsmall cell lung cancer, has 2 main active metabolites, AZ5104 and AZ7550, which demonstrate potency against wild-type epidermal growth factor receptor mutations. In this study, a simple and sensitive analytical method using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/mass spectrometry) was developed and validated to simultaneously quantify osimertinib and its active metabolites in human plasma. Plasma samples were subjected to protein precipitation with zinc sulfate solution and acetonitrile using osimertinib- 13 C, d 3 as an internal standard. The separation was performed on a ThermoScientific Hypersil GOLD C18 column (4.6 × 50 mm, 5 μm) with a mobile phase composed of 0.1% formic acid water-acetonitrile through gradient elution. The compounds were monitored using electrospray ionization in the positive mode with multiple reaction monitoring. Excellent linearity of calibration curves was observed over the ranges of 10-1000 ng·mL -1 for osimertinib, and 1.5-120 ng·mL -1 for AZ7550 and AZ5104 in human plasma. Both within-run and between-run accuracies were within ±15%, with the coefficient of variation <15%. The method met all the validation criteria and was successfully applied to clinical samples from patients with nonsmall cell lung cancer. Furthermore, the correlation between steady-state trough concentrations of osimertinib, AZ5104, and AZ7550 and patients' baseline characteristics were explored. Women exhibited a significantly higher C min, ss for AZ7550 ( P = 0.023). In addition, body mass index was associated with the C min, ss of both AZ5104 ( P = 0.047) and AZ7550 ( P = 0.001).

Circulating biomarkers predict platelet recovery in adult dengue patients with thrombocytopenia receiving prophylactic platelet transfusion.

IgA nephropathy (IgAN) is one of the most prevalent glomerulonephropathies and commonly leads to kidney failure. The recurrence of IgAN following transplantation remains a significant concern. Currently, detecting IgAN recurrence requires a kidney biopsy, highlighting the need for non-invasive biomarkers such as donor-derived cell-free DNA (dd-cfDNA) to aid in early detection. This prospective pilot study aims to evaluate dd-cfDNA as a non-invasive biomarker for detecting IgAN recurrence post-kidney transplantation. Specifically, the study seeks to compare %dd-cfDNA levels in transplanted patients with and without IgAN recurrence and correlate these levels with other kidney function parameters. A total of 32 patients with histologically confirmed IgAN were enrolled, including those with documented IgAN recurrence post-transplantation and those without recurrence. Plasma samples were collected and processed using the AlloSeq cfDNA kit to quantify relative %dd-cfDNA levels. Kidney function parameters, including estimated glomerular filtration rate (eGFR) and proteinuria, were also assessed. The study found no significant difference in %dd-cfDNA levels between transplanted patients with IgAN recurrence and those without recurrence (median 0.37% [IQR 0.28%-3.53%] vs. median 0.42% [IQR 0.15%-0.84%], p = 0.67). Also, %dd-cfDNA (AUC = 0.57 [95% CI 0.28-0.85], p = 0.64) failed to effectively discriminate IgAN recurrence compared to traditional kidney function parameters such as proteinuria (AUC = 0.96 [95% CI 0.87-1.00], p = 0.002) and eGFR (AUC = 0.74 [95% CI 0.47-1.00], p = 0.09). Relative (%) dd-cfDNA alone may not be a robust biomarker for detecting IgAN recurrence post-transplantation. While proteinuria proved a more effective indicator in this study, kidney biopsy remains the gold standard for definitive diagnosis. These findings highlight the challenges of using %dd-cfDNA as a standalone diagnostic tool for monitoring IgAN recurrence post-transplantation. Future research should explore larger patient cohorts and longitudinal assessments to refine the utility of dd-cfDNA and investigate potential combination strategies with other biomarkers.

Long-term storage stability of plasma TNF-α and IL-6 concentrations of psychiatric emergency patients: The Signature Biobank.

Detection of erythropoietin in blood plasma through an SPRi-based biosensor.

Development and Validation of Novel Cell-free Direct Neutralization Assay for SARS-CoV-2.

Associations of plasma inosine with lipid parameters in a biracial community cohort.

Profiling lipidomic variations in primary open-angle and angle-closure glaucoma patients.

Development of a pseudotargeted metabolomics approach for relative quantification of free fatty acid double-bond isomers in beagle plasma.