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Liquid chromatography with mass spectrometry (LC-MS)-based metabolomics detects thousands of molecular features (retention time-m/z pairs) in biological samples per analysis, yet the metabolite annotation rate remains low, with 90% of signals classified as unknowns. To enhance the metabolite annotation rates, researchers employ tandem mass spectral libraries and challenging in silico fragmentation software. Hydrogen/deuterium exchange mass spectrometry (HDX-MS) may offer an additional layer of structural information in untargeted metabolomics, especially for identifying specific unidentified metabolites that are revealed to be statistically significant. Here, we investigate the potential of hydrophilic interaction liquid chromatography (HILIC)-HDX-MS in untargeted metabolomics. Specifically, we evaluate the effectiveness of two approaches using hypothetical targets: the post-column addition of deuterium oxide (D2O) and the on-column HILIC-HDX-MS method. To illustrate the practical application of HILIC-HDX-MS, we apply this methodology using the in silico fragmentation software MS-FINDER to an unknown compound detected in various biological samples, including plasma, serum, tissues, and feces during HILIC-MS profiling, subsequently identified as N1-acetylspermidine.

Liquid chromatography-mass spectrometry (LC-MS) is the key technique for analyzing complex lipids in biological samples. Various LC-MS modes are used for lipid separation, including different stationary phases, mobile-phase solvents, and modifiers. Quality control in lipidomics analysis is crucial to ensuring the generated datas reliability, reproducibility, and accuracy. While several quality control measures are commonly discussed, the impact of organic solvent quality during LC-MS analysis is often overlooked. Additionally, the annotation of complex lipids remains prone to biases, leading to potential misidentifications and incomplete characterization of lipid species. In this study, we investigate how LC-MS-grade isopropanol from different vendors may influence the quality of the mobile phase used in LC-MS-based untargeted lipidomic profiling of biological samples. Furthermore, we report the occurrence of an unusual, yet highly abundant, ethylamine adduct [M+46.0651]+ that may form for specific lipid subclasses during LC-MS analysis in positive electrospray ionization mode when acetonitrile is part of the mobile phase, potentially leading to lipid misidentification. These findings emphasize the importance of considering solvent quality in LC-MS analysis and highlight challenges in lipid annotation.

Prestressing of bridges allows construction of long spanned bridges made from thin structural members with high flexural and shear capacity. Studies have shown that some of the existing prestressed bridges are not meeting their designed service life due to corrosion of the tendons. The main reasons are poor construction practices in combination with inadequate inspection and maintenance plans. This paper provides a summary of repair options for corrosion-damaged prestressed concrete structures with focus on the individual components of the prestressed system. The applicability of identified repair options to Norwegian conditions is discussed.

Thermal reactions can significantly alter the metabolomic and lipidomic content of biofluids and tissues during storage. In this study, we investigated the stability of polar metabolites and complex lipids in dry human serum and mouse liver extracts over a three-day period under various temperature conditions. Specifically, we tested temperatures of -80 °C (freezer), -24 °C (freezer), -0.5 °C (polystyrene box with gel-based ice packs), +5 °C (refrigerator), +23 °C (laboratory, room temperature), and +30 °C (thermostat) to simulate the time between sample extraction and analysis, shipping dry extracts to different labs as an alternative to dry ice, and document the impact of higher temperatures on sample integrity. The extracts were analyzed using five fast liquid chromatography-mass spectrometry (LC-MS) methods to screen polar metabolites and complex lipids, and over 600 metabolites were annotated in serum and liver extracts. We found that storing dry extracts at -24 °C and partially at -0.5 °C provided comparable results to -80 °C (reference condition). However, increasing the storage temperatures led to significant changes in oxidized triacylglycerols, phospholipids, and fatty acids within three days. Polar metabolites were mainly affected at storage temperatures of +23 °C and +30 °C.

A broad spectrum, total of 195 microfungal taxa, were isolated from various cave substrates (cave air, cave sediments, bat droppingsand/or guano, earthworm casts, isopods and diplopods faeces, mammalian dung, cadavers, vermiculations, insect bodies, plantmaterial, etc.) from the cave system of the Domica Cave (Slovak Karst National Park, Slovakia) using dilution, direct and gravitysettling culture plate methods and several isolation media. Penicillium glandicola, Trichoderma polysporum, Oidiodendron cerealis,Mucor spp., Talaromyces flavus and species of the genus Doratomyces were isolated frequently during our study. Estimatedmicrofungal species diversity was compared with literature records from the same substrates published in the past.

The microfungus Pidoplitchkoviella terricola – until now it was known only as Kirilenko´s specimen isolated from Quercusrobur rhizosphere in Ukraine - was found in earthworm casts in the Domica Cave, NP Slovak Karst, Slovakia. A description andmicrophotographs of this strain are provided in this article.

In regulatory laboratories, where potentially hundreds of different types of sample and active ingredients can be evaluated every year, a unique set of conditions provided by agricultural product manufacturers in their regulatory methods are faced with the decision to purchase a new and different analytical column or not follow the enforcement method provided by the manufacturer. Because of this, a multi-analyte method has been developed at the Irish Department of Agriculture, Food and The Marine, contributed to by the regulatory laboratories in Belgium and the Czech Republic, analyzing more than 70 active ingredients using high performance liquid chromatography (HPLC) and more than 35 active ingredients by ultrahigh-pressure liquid chromatography (UHPLC). The method has been designed for use by quality control laboratories and is suitable for determining a range of active substances in a wider range of formulated products as well as the technical AI itself. The method has been validated for linearity, precision, accuracy, and specificity for seven technical active ingredients as defined by FMC Corporation. The method and results are described in this article., In the pesticide industry, regulatory laboratories are responsible for the quality of the material sold in the open market. Laboratories receive samples from the open trade that are sold in [...]

Abstract Background Standard measures of response such as Response Evaluation Criteria in Solid Tumors are ineffective for bone lesions, often making breast cancer patients that have bone-dominant metastases ineligible for clinical trials with potentially helpful therapies. In this study we prospectively evaluated the test-retest uptake variability of 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG) in a cohort of breast cancer patients with bone-dominant metastases to determine response criteria. The thresholds for 95% specificity of change versus no-change were then applied to a second cohort of breast cancer patients with bone-dominant metastases. Methods For this study, nine patients with 38 bone lesions were imaged with 18F-FDG in the same calibrated scanner twice within 14 days. Tumor uptake was quantified by the most commonly used PET parameter, the maximum tumor voxel normalized by dose and body weight (SUVmax) and also by the mean of a 1-cc maximal uptake volume normalized by dose and lean-body-mass (SULpeak). The asymmetric repeatability coefficients with confidence intervals for SUVmax and SULpeak were used to determine the limits of 18F-FDG uptake variability. A second cohort of 28 breast cancer patients with bone-dominant metastases that had 146 metastatic bone lesions was imaged with 18F-FDG before and after standard-of-care therapy for response assessment. Results The mean relative difference of SUVmax and SULpeak in 38 bone tumors of the first cohort were 4.3% and 6.7%. The upper and lower asymmetric limits of the repeatability coefficient were 19.4% and − 16.3% for SUVmax, and 21.2% and − 17.5% for SULpeak. 18F-FDG repeatability coefficient confidence intervals resulted in the following patient stratification using SULpeak for the second patient cohort: 11-progressive disease, 5-stable disease, 7-partial response, and 1-complete response with three inevaluable patients. The asymmetric repeatability coefficients response criteria for SULpeak changed the status of 3 patients compared to the standard Positron Emission Tomography Response Criteria in Solid Tumors of ± 30% SULpeak. Conclusion In evaluating bone tumor response for breast cancer patients with bone-dominant metastases using 18F-FDG SUVmax, the repeatability coefficients from test-retest studies show that reductions of more than 17% and increases of more than 20% are unlikely to be due to measurement variability. Serial 18F-FDG imaging in clinical trials investigating bone lesions in these patients, such as the ECOG-ACRIN EA1183 trial, benefit from confidence limits that allow interpretation of response.

Abstract In recent decades, we have seen significant technical progress in the modern world, leading to the widespread use of telecommunications systems, electrical appliances, and wireless technologies. These devices generate electromagnetic radiation (EMR) and electromagnetic fields (EMF) most often in the extremely low frequency or radio-frequency range. Therefore, they were included in the group of environmental risk factors that affect the human body and health on a daily basis. In this study, we tested the effect of exposure EMF generated by a new prototype wireless charging system on four human cell lines (normal cell lines—HDFa, NHA; tumor cell lines—SH-SY5Y, T98G). We tested different operating parameters of the wireless power transfer (WPT) device (87–207 kHz, 1.01–1.05 kW, 1.3–1.7 mT) at different exposure times (pulsed 6 × 10 min; continuous 1 × 60 min). We observed the effect of EMF on cell morphology and cytoskeletal changes, cell viability and mitotic activity, cytotoxicity, genotoxicity, and oxidative stress. The results of our study did not show any negative effect of the generated EMF on either normal cells or tumor cell lines. However, in order to be able to estimate the risk, further population and epidemiological studies are needed, which would reveal the clinical consequences of EMF impact.

Abstract Background We investigated the effect of obesity on the association of genome-wide associative studies (GWAS)-significant genes with the risk of knee osteoarthritis (KOA). Methods All study participants (n = 1,100) were divided into 2 groups in terms of body mass index (BMI): BMI ≥ 30 (255 KOA patients and 167 controls) and BMI

Introduction: Digital breast tomosynthesis (DBT) may improve sensitivity in population screening. However, evidence is currently limited on the performance of DBT in patients at a higher risk of breast cancer. This systematic review compares the clinical effectiveness and cost-effectiveness of DBT, digital mammography (DM), and ultrasound, for breast cancer detection in women with dense breasts and additional risk factors. Methods: Medline, Embase, and Evidence-Based Medicine Reviews via OvidSP were searched to identify literature from 2010 to August 21, 2023. Selection of studies, data extraction, and quality assessment (using QUADAS-2 and CHEERS) were completed in duplicate. Findings were summarised descriptively and narratively. Results: Twenty-six studies met pre-specified inclusion criteria. In women with breast symptoms or recalled for investigation of screen-detected findings (19 studies), DBT may be more accurate than DM. For example, in symptomatic women, the sensitivity of DBT + DM ranged from 82.8 % to 92.5 % versus 56.8 %–81.3 % for mammography (DM/synthesised images). However, most studies had a high risk of bias due to participant selection. Evidence regarding DBT in women with a personal or family history of breast cancer, for DBT versus ultrasound alone, and cost-effectiveness of DBT was limited. Conclusions: In women with dense breasts and additional risk factors for breast cancer, evidence is limited about the accuracy of DBT compared to other imaging modalities, particularly in those with personal or family history of breast cancer. Future research in this population should consider head-to-head comparisons of imaging modalities to determine the relative effectiveness of these imaging tests. Systematic review registration: PROSPERO registration number CRD42021236470.

This article provides an overview of the materials used to manufacture magnesium wheels for light vehicles. The analysis was conducted with the aim of developing a new, efficient technology for molding magnesium alloy wheels for light vehicles from preforms cast into metal molds. The knowledge accumulated so far on materials and their properties for the production of magnesium wheels will allow the design of a new technology for molding rims from materials of superior quality and durability. Currently, magnesium wheels are mainly produced from cast magnesium alloys and magnesium alloys for forming. Cast magnesium alloys used for magnesium wheels include AZ91, AM50, AM60, AE44, ZK61, ZE41, EZ33, EQ21, WE43 and the newly developed Mg-2.96Nd-0.21Zn-0.39Zr alloy. Magnesium metal-forming alloys used for magnesium wheels include AZ31, AZ61, AZ80 and ZK30, ZK60. The study includes an analysis of their properties and application examples.

Abstract Purpose To investigate combined MRI and 18F-FDG PET for assessing breast tumor metabolism/perfusion mismatch and predicting pathological response and recurrence-free survival (RFS) in women treated for breast cancer. Methods Patients undergoing neoadjuvant chemotherapy (NAC) for locally-advanced breast cancer were imaged at three timepoints (pre, mid, and post-NAC), prior to surgery. Imaging included diffusion-weighted and dynamic contrast-enhanced (DCE-) MRI and quantitative 18F-FDG PET. Tumor imaging measures included apparent diffusion coefficient, peak percent enhancement (PE), peak signal enhancement ratio (SER), functional tumor volume, and washout volume on MRI and standardized uptake value (SUVmax), glucose delivery (K1) and FDG metabolic rate (MRFDG) on PET, with percentage changes from baseline calculated at mid- and post-NAC. Associations of imaging measures with pathological response (residual cancer burden [RCB] 0/I vs. II/III) and RFS were evaluated. Results Thirty-five patients with stage II/III invasive breast cancer were enrolled in the prospective study (median age: 43, range: 31–66 years, RCB 0/I: N = 11/35, 31%). Baseline imaging metrics were not significantly associated with pathologic response or RFS (p > 0.05). Greater mid-treatment decreases in peak PE, along with greater post-treatment decreases in several DCE-MRI and 18F-FDG PET measures were associated with RCB 0/I after NAC (p

Abstract NanoLuc, a superior β-barrel fold luciferase, was engineered 10 years ago but the nature of its catalysis remains puzzling. Here experimental and computational techniques are combined, revealing that imidazopyrazinone luciferins bind to an intra-barrel catalytic site but also to an allosteric site shaped on the enzyme surface. Structurally, binding to the allosteric site prevents simultaneous binding to the catalytic site, and vice versa, through concerted conformational changes. We demonstrate that restructuration of the allosteric site can boost the luminescent reaction in the remote active site. Mechanistically, an intra-barrel arginine coordinates the imidazopyrazinone component of luciferin, which reacts with O2 via a radical charge-transfer mechanism, and then it also protonates the resulting excited amide product to form a light-emitting neutral species. Concomitantly, an aspartate, supported by two tyrosines, fine-tunes the blue color emitter to secure a high emission intensity. This information is critical to engineering the next-generation of ultrasensitive bioluminescent reporters.

Abstract Moderate cold acclimation (MCA) is a non-invasive intervention mitigating effects of various pathological conditions including myocardial infarction. We aim to determine the shortest cardioprotective regimen of MCA and the response of β1/2/3-adrenoceptors (β-AR), its downstream signaling, and inflammatory status, which play a role in cell-survival during myocardial infarction. Adult male Wistar rats were acclimated (9 °C, 1–3-10 days). Infarct size, echocardiography, western blotting, ELISA, mitochondrial respirometry, receptor binding assay, and quantitative immunofluorescence microscopy were carried out on left ventricular myocardium and brown adipose tissue (BAT). MultiPlex analysis of cytokines and chemokines in serum was accomplished. We found that short-term MCA reduced myocardial infarction, improved resistance of mitochondria to Ca2+-overload, and downregulated β1-ARs. The β2-ARs/protein kinase B/Akt were attenuated while β3-ARs translocated on the T-tubular system suggesting its activation. Protein kinase G (PKG) translocated to sarcoplasmic reticulum and phosphorylation of AMPKThr172 increased after 10 days. Principal component analysis revealed a significant shift in cytokine/chemokine serum levels on day 10 of acclimation, which corresponds to maturation of BAT. In conclusion, short-term MCA increases heart resilience to ischemia without any negative side effects such as hypertension or hypertrophy. Cold-elicited cardioprotection is accompanied by β1/2-AR desensitization, activation of the β3-AR/PKG/AMPK pathways, and an immunomodulatory effect.