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Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected over 21 million people worldwide since August 16, 2020. Compared to PCR and serology tests, SARS-CoV-2 antigen assays are underdeveloped, despite their potential to identify active infection and monitor disease progression. Methods We used Single Molecule Array (Simoa) assays to quantitatively detect SARS-CoV-2 spike, S1 subunit, and nucleocapsid antigens in the plasma of patients with coronavirus disease (COVID-19). We studied plasma from 64 patients who were COVID-19 positive, 17 who were COVID-19 negative, and 34 prepandemic patients. Combined with Simoa anti-SARS-CoV-2 serological assays, we quantified changes in 31 SARS-CoV-2 biomarkers in 272 longitudinal plasma samples obtained for 39 patients with COVID-19. Data were analyzed by hierarchical clustering and were compared to longitudinal RT-PCR test results and clinical outcomes. Results SARS-CoV-2 S1 and N antigens were detectable in 41 out of 64 COVID-19 positive patients. In these patients, full antigen clearance in plasma was observed a mean ± 95% CI of 5 ± 1 days after seroconversion and nasopharyngeal RT-PCR tests reported positive results for 15 ± 5 days after viral-antigen clearance. Correlation between patients with high concentrations of S1 antigen and ICU admission (77%) and time to intubation (within 1 day) was statistically significant. Conclusions The reported SARS-CoV-2 Simoa antigen assay is the first to detect viral antigens in the plasma of patients who were COVID-19 positive to date. These data show that SARS-CoV-2 viral antigens in the blood are associated with disease progression, such as respiratory failure, in COVID-19 cases with severe disease.

A highly selective, sensitive caffeic acid (CA) detection based on calcium oxide nanoparticles (CaO NPs) derived from extract of Moringa oleifera leaves decorated graphitic carbon nitride covalently grafted poly vinyl alcohol (CaO/g-C 3 N 4 /PVA) nanocomposite modified glassy carbon electrode (GCE) was studied. A facile sonochemical method was adapted to synthesis nanomaterials and characterized by HR-TEM (High resolution transmission electron microscopy), FT-IR (Fourier transform infrared spectroscopy), XRD (X-ray diffraction), FE-SEM (Field emission scanning electron microscopy), EDX (Energy dispersive X-ray analysis), Mapping and BET (Brunauer-Emmett-Teller) analysis, and electrochemical techniques. The nanocomposite modified GCE exhibited an excellent catalytic performance to the oxidation of CA under optimized conditions owing to better electron transfer efficiency, conductivity and high surface area of the electrode material. The present electrochemical sensor showed high selectivity towards the determination of 10 µM CA in the presence of 100-fold higher concentrations of interferents. The modified CA sensor exhibited a wide sensing linear range from 0.01 µM to 70 µM and the detection limit (LOD) was found to be 0.0024 µM (S/ N  = 3) in 0.1 M phosphate buffer saline (PBS) as a supporting electrolyte at pH 7.0. The fabricated CA sensor provides an excellent stability, reproducibility and selectivity for the determination of CA. The modified CA sensor was applied to real blood plasma samples and obtained good recovery (97.6-100.1%) results.

Objective This study was planned to determine the efficacies of single plasma sample methods (SPSMs) in indicating glomerular filtration rate (GFR) by taking two plasma sample method (TPSM) as reference in the determination of the GFR in cases with clinically stable renal transplantation. Methods Ninety-six renal transplantation cases (33 female, 63 male; age interval 18–67, mean age 37.46 ± 11.81 years) progressing stably clinically and as laboratory, with minimum 6 months after transplantation were included in the study. The GFR values of the cases were measured with SPSM and TPSM. Results It is observed that all SPSMs have a strong correlation with TPSM. Highest correlation was observed between Groth&Aasted SPSM and TPSM GFR (intraclass correlation coefficient: 0.965). In the analyses performed by using the Bland–Altman analysis, GFR values calculated by all SPSMs were concordant to the TPSM which is the gold standard method in 95 % confidence interval (average ± 1.96 standard deviation) and were within the clinically acceptable limits. The narrowest concordance interval was obtained between Groth&Aasted Tc-99 m DTPA SPSM and Tc-99 m DTPA TPSM..Besides, we have obtained the minimum bias and precision value by the Groth&Aasted method. Conclusions As a result; we can see that all the SPSMs give reliable results in measuring GFR in cases with renal transplantation; besides, we suggest Groth&Aasted method as the first option.

Glioblastoma (GB) is the most aggressive and frequent primary malignant tumor of the central nervous system and is associated with poor overall survival even after treatment. To better understand tumor biochemical alterations and broaden the potential targets of GB, this study aimed to evaluate differential plasma biomarkers between GB patients and healthy individuals using metabolomics analysis. Plasma samples from both groups were analyzed via untargeted metabolomics using direct injection with an electrospray ionization source and an LTQ mass spectrometer. GB biomarkers were selected via Partial Least Squares Discriminant and Fold-Change analyses and were identified using tandem mass spectrometry with in silico fragmentation, consultation of metabolomics databases, and a literature search. Seven GB biomarkers were identified, some of which were unprecedented biomarkers for GB, including arginylproline (m/z 294), 5-hydroxymethyluracil (m/z 143), and N-acylphosphatidylethanolamine (m/z 982). Notably, four other metabolites were identified. The roles of all seven metabolites in epigenetic modulation, energy metabolism, protein catabolism or folding processes, and signaling pathways that activate cell proliferation and invasion were elucidated. Overall, the findings of this study highlight new molecular targets to guide future investigations on GB. These molecular targets can also be further evaluated to derive their potential as biomedical analytical tools for peripheral blood samples.

Meningiomas (MGMs) are currently classified into grades I, II, and III. High-grade tumors are correlated with decreased survival rates and increased recurrence rates. The current grading classification is based on histological criteria and determined only after surgical tumor sampling. This study aimed to identify plasma metabolic alterations in meningiomas of different grades, which would aid surgeons in predefining the ideal surgical strategy. Plasma samples were collected from 51 patients with meningioma and classified into low-grade (LG) (grade I; n = 43), and high-grade (HG) samples (grade II, n = 5; grade III, n = 3). An untargeted metabolomic approach was used to analyze plasma metabolites. Statistical analyses were performed to select differential biomarkers among HG and LG groups. Metabolites were identified using tandem mass spectrometry along with database verification. Five and four differential biomarkers were identified for HG and LG meningiomas, respectively. To evaluate the potential of HG MGM metabolites to differentiate between HG and LG tumors, a receiving operating characteristic curve was constructed, which revealed an area under the curve of 95.7%. This indicates that the five HG MGM metabolites represent metabolic alterations that can differentiate between LG and HG meningiomas. These metabolites may indicate tumor grade even before the appearance of histological features.

Polyphenols are an important class of secondary metabolites that possess antioxidant or anti-inflammatory properties and are associated with many health benefits. It has been reported that extracts of fruit juices or the fruit juices themselves are able to influence lipid metabolism. The aims of this study were to establish a reliable analytical method and thereafter investigate the influence of a polyphenol-rich fruit juice during an eight-week intervention on plasma lipid profiles in healthy male subjects. A placebo-controlled intervention study with 36 healthy male subjects was carried out. Volunteers consumed 750 mL of a polyphenol-rich or placebo beverage on a daily basis. With the established untargeted LC-IMS-qTof method, lipids could be identified, and changes in the lipidome could be detected. For the first time, a comparison of the lipidome of the control vs. treatment group allowed for the identification of differences in lipid profiles. The observed changes suggest that polyphenol intake leads to the targeted re-modeling of the lipidome, affecting bioactive lipid mediators and membrane components in particular. In the future, our identified lipid markers may be established as potential biomarker candidates related to health.

Dilated cardiomyopathy is one of the important diseases in dogs and humans. The second most common cause of heart failure in dogs is idiopathic dilated cardiomyopathy (iDCM), which results in heart failure or sudden cardiac death due to arrhythmia. This study aimed to determine changes in the plasma metabolome of dogs with iDCM compared to healthy dogs. For that purpose, a multiplatform mass-spectrometry-based approach was used. In this study, we included two groups of dogs: 12 dogs with iDCM and 8 healthy dogs. A total of 272 metabolites were detected in the plasma samples of dogs by combining three approaches but four MS-based platforms (GC-MS, LC-MS (untargeted), LC-MS (targeted), and FIA-MS (targeted) methods). Our findings demonstrated changes in the canine plasma metabolome involved in the development of iDCM, including the different concentrations of amino acids, biogenic amines, acylcarnitines, triglycerides and diglycerides, sphingomyelins, and organic acids. The results of this study will enable the detection and monitoring of pathophysiological mechanisms involved in the development of iDCM in the future.

Lafora progressive myoclonus epilepsy (LD, OMIM#254780, ORPHA:501) is an ultra-rare and severe autosomal recessive neurological disorder that typically manifests in early adolescence. It is characterized by the accumulation of insoluble forms of aberrant glycogen in the brain and peripheral tissues. Given the urgent need for reliable tools to monitor disease progression, we aimed to identify reliable biomarkers in minimally invasive fluids, which could also provide valuable insights into the natural history of the disease. Plasma-EDTA samples from eleven LD patients and healthy controls were analyzed to identify potential biomarkers of LD using a high-throughput assay. The findings were subsequently validated using specific enzyme-linked immunosorbent assays (ELISAs). Eleven cytokines and growth factors were identified to be significantly reduced in LD patient samples compared to healthy controls. Among these, four mediators [platelet-derived growth factor subunit B (PDGF-BB), epidermal growth factor (EGF), brain derived growth factor (BDNF), and macrophage migration inhibitory factor (MIF)] exhibited the greatest fold change between the groups and were further validated. Given the minimally invasive nature of plasma sampling and the straightforward quantification via ELISA assays, these biomarkers hold strong promise for rapid translation to the clinic, potentially enhancing early diagnosis and longitudinal disease monitoring in LD patients.

This paper summarizes the main findings of a study which aimed to examine the electrochemical oxidation of homovanillic acid (HVA), the final metabolite of dopamine. A pencil graphite electrode (PGE) was used as working electrode and the measurements were performed by cyclic voltammetry (CV) and differential pulse voltammetry (DPV). The type and the composition of the graphite leads used as PGE, the pH of the supporting electrolyte, as well as the scan rates were optimized by CV. The analyte was irreversibly oxidized in Britton–Robinson buffer (BRB) solutions. The interpretation of the voltammetric signals and the correlation of the acquired information were the key to addressing the electrode process undergone by HVA at the PGE. The outcomes of the pH and scan rate studies led to the conclusion that two electrons and two protons were involved in the diffusion-controlled process. Using the PGE, a linear relationship between peak current and HVA concentration was obtained between 1.0 × 10−6 M and 5.0 × 10−5 M by DPV in BRB with pH 2.0. The detection limit of 3.84 × 10−7 M was calculated. The accuracy, the precision, and the selectivity of the quantitative method have successfully undergone evaluation. The practical application of the developed voltammetric method was checked by determining the HVA concentration in spiked plasma samples, yielding good recovery values.

•Methamphetamine can be synthesized either enantiopure or in its racemic form.•Separation of (R)- and (S)-enantiomers of methamphetamine eby LC–MS/MS.•succesful validation for qualitative detection.•99% of tested samples from Germany only (S)-methamphetamine was detected. Methamphetamine can be synthesized either enantiopure or in its racemic form. We separated (R)- and (S)-enantiomers of methamphetamine and amphetamine by a fast LC–MS/MS-method using a Lux® 3μm AMP 150×3.0mm analytical column after simple protein precipitation with methanol. Sufficient resolution could be achieved. Method validation for qualitative detection showed limits of quantification <5ng/mL while only little (maximum 14.5%) ion suppression could be shown. Stability in the processed sample could be achieved using isotopically labelled internal standards. Plasma samples of police cases from the german regions of Franconia and Northrhine revealed that in the majority of 106 tested samples (>99%) only (S)-methamphetamine was detected which leads to the conclusion that, in Germany, predominantly enantiopure (S)-methamphetamine is consumed which is synthesized via (1R,2S)-ephedrine or (1S,2S)-pseudoephedrine. However, racemic methamphetamine seems also to be on the market.