bluuebunny/crossref_metadata_2025_split huggingface dataset:
LC–MS/MS quantification of olanzapine in hair after alkaline digestion
Authors: Turkmen Zeynep , Arslan Zeynep , Oka Merve , Yayla Murat , Bavunoglu Isil 
Published: June 2024

AbstractOlanzapine (OLZ), a second‐generation antipsychotic drug, is effective in the treatment of acute psychosis, schizophrenia, agitation, bipolar mania, and other psychiatric problems. Antipsychotics are prescribed drugs, which lead the drug abuser to illegal methods of access. This behavior also demonstrates the association of OLZ with criminal involvement, commonly observed at forensic crime scenes. The acute toxicity and even death resulting from OLZ exposure have been highlighted in numerous studies. Therefore, developing analytical techniques to detect OLZ is essential for forensic toxicology. This study aimed to develop a specific and reliable LC–MS/MS method for OLZ detection and quantification in hair samples. The method was validated in terms of selectivity, linearity, limit of detection (LOD), limit of quantification (LOQ), trueness, precision, and uncertainty. The range of linearity was between 0.1–100 ng/mg, with LOD and LOQ values established at 0.036 ng/mg and 0.1 ng/mg, respectively. All validation results are within acceptable parameters. The validated method has been applied to authentic hair samples. The variation of OLZ concentrations in 12 hair segments (2 from Case 1 and 10 from Case 2) from two drug‐positive patients, ranging from 0.131 to 0.460 ng/mg, is presented in this study. Although several studies have been conducted to determine OLZ in hair samples using segmental analysis via hair solubilization, this study is the first to determine OLZ in hair samples after “digestion” with comparative parameters prior to chromatographic analysis.
Differential impacts of nonsteroidal anti‐inflammatory drugs on lifespan and healthspan in aged Caenorhabditis elegans
Authors: Tu Jia‐Jun , Yu Zhen‐Zhen , Ou Mei‐Ling , Cen Jin‐Xiong , Xue Kun , Zhou Jing , Li Shao‐Jun , Lu Guo‐Dong 
Published: June 2024

AbstractAging and age‐related diseases are intricately associated with oxidative stress and inflammation. Nonsteroidal anti‐inflammatory drugs (NSAIDs) have shown their promise in mitigating age‐related conditions and potentially extending lifespan in various model organisms. However, the efficacy of NSAIDs in older individuals may be influenced by age‐related changes in drug metabolism and tolerance, which could result in age‐dependent toxicities. This study aimed to evaluate the potential risks of toxicities associated with commonly used NSAIDs (aspirin, ibuprofen, acetaminophen, and indomethacin) on lifespan, healthspan, and oxidative stress levels in both young and old Caenorhabditis elegans. The results revealed that aspirin and ibuprofen were able to extend lifespan in both young and old worms by suppressing ROS generation and enhancing the expression of antioxidant SOD genes. In contrast, acetaminophen and indomeacin accelerated aging process in old worms, leading to oxidative stress damage and reduced resistance to heat stress through the pmk‐1/skn‐1 pathway. Notably, the harmful effects of acetaminophen and indomeacin were mitigated when pmk‐1 was knocked out in the pmk‐1(km25) strain. These results underscore the potential lack of benefit from acetaminophen and indomeacin in elderly individuals due to their increased susceptibility to toxicity. Further research is essential to elucidate the underlying mechanisms driving these age‐dependent responses and to evaluate the potential risks associated with NSAID use in the elderly population.
The quality of frozen–thawed Atlantic salmon (Salmo salar L.) fillets as affected by sub‐chilling before freezing
Authors: Lerfall Jørgen , Vangen Emma , Rotabakk Bjørn Tore 
Published: June 2024

AbstractBackgroundTo maintain the quality of frozen Atlantic salmon after thawing and highlight the potential for moving from air fright to boat for long‐distance export, a study was designed to investigate the effects of sub‐chilling before rapid freezing on the quality of thawed fillets. Atlantic salmon chilled on wet ice before filleting and freezing was used as a control for the experimental factor chilling, whereas fresh fillets were used for the frozen–thawed samples.ResultsThe pre‐freezing chilling method interacted with the storage protocol and significantly affected the product. For fresh stored fillets, sub‐chilling improved the microbiological and textural stability and degradation of proteins. After 1 month of frozen storage, sub‐chilled fillets gave better color and textural properties, less adenosine triphosphate degradation and protein denaturation. In addition, sub‐chilled 4‐month‐frozen fillets also showed improved microbial stability compared to those initially chilled with ice before frozen storage. Quality was lost as a function of storage. Fresh fillets generally had higher bacterial counts, surface breaking force, firmness, hue and contents of inosine monophosphate, and lower drip loss and inosine (HxR) levels than those stored frozen–thawed. Moreover, 4‐month‐frozen fillets had higher HxR levels and lower psychrotrophic viable count growth than those that were frozen for 1 month. The time fillets were stored frozen did not profoundly affect their quality.ConclusionIt is concluded that a frozen product might be competitive with a fresh product when sub‐chilling is performed before freezing, especially when including the environmental benefits of frozen export by boat rather than air freight. © 2024 The Author(s). Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
The Impact of Race and the Affordable Care Act on Thyroid Carcinoma Outcomes: A National Cancer Database Study
Authors: Nurimba Margaret , Sheth Megha , Swanson Mark , Chambers Tamara 
Published: June 2024

ObjectiveTo assess the impact of race and the Affordable Care Act (ACA) of 2010 on disease presentation and overall survival for patients with well‐differentiated thyroid carcinoma.Study DesignCross‐sectional study of patients (n = 51,078) who underwent partial or total thyroidectomy with or without postoperative radioactive iodine (RAI) for well‐differentiated thyroid carcinoma between 2004 and 2018 in the National Cancer Database (NCDB).MethodsCumulative survival (CS) was assessed with Cox proportional hazard regression analyses.ResultsThere were significant disparities in disease presentation at the time of diagnosis, with Black, Asian/Pacific Islander (API), and Hispanic patients were more likely to have metastatic disease (p < 0.001) and higher TNM stage (p < 0.001) at the time of diagnosis compared to White patients. Black patients had significantly increased risk of death (HR 1.147, 95%CI 1.021–1.289) but API patients had improved CS (HR 0.730, 95% CI 0.608–0.877) compared to White patients. Passage of the ACA was associated with lower risk of mortality, regardless of whether patients lived in states that did not expand Medicaid (HR 0.866, 95% CI 0.823–0.910) or whether they lived in expansion states (HR 0.818, 95% CI 0.758–0.884).ConclusionRacial disparities significantly impact thyroid carcinoma diagnosis and treatment in the United States but have improved over time. Both expansion and non‐expansion states had improved survival outcomes over time, and suggesting analysis of the ACA's long‐term impact and ability to address health inequities is still warranted.Level of Evidence3 Laryngoscope, 134:4421–4430, 2024
A hemodynamic study of the relationship between the left and right liver volumes and the blood flow distribution in portal vein branches
Authors: Xie Chiyu , Sun Shengda , Huang Hao , Li Xiaofan , Qu Wei , Song Hongqing 
Published: June 2024

AbstractBackgroundCirrhosis patients often exhibit clinical symptoms such as right liver atrophy, portal hypertension, spleen enlargement and increased blood supply, which exhibit considerable variation between the left and right liver sections. These differences are hypothesized to stem from disparities in blood flow within the left and right portal vein (PV) branches. However, rigorous quantitative evidence remains scarce.PurposeWe mainly aim at quantitatively revealing the relationship between the blood flow rates of two PV branches and liver volumes, and providing quantitative evidence and theoretical support for the diagnosis and treatment of cirrhosis from the perspective of hemodynamics.MethodsFive cirrhotic patients and two healthy volunteers from Beijing Friendship Hospital are investigated. Their PV blood flow models are established based on computed tomography (CT) images and finite volume simulations. The volume of the left and right liver lobes are measured in 3‐matic. The distributions of blood source in the PV branches are tracked by streamline analysis. The blood flow rates are quantitatively counted by integrating the blood source velocities. Linear analysis is performed to build the relationship between liver volumes and PV blood flow distributions.ResultsStreamline analysis reveals significant differences in blood distribution between the left and right PV branches. The majority of blood from the superior mesenteric vein (SMV) flowed into the right portal vein (RPV), while most blood from the splenic vein (SV) entered the left portal vein (LPV). The main PV pressure drop linearly increases with the SV blood velocity for all PV structures of patients and healthy volunteers. The flow rate ratio QRPV/QLPV demonstrates an increase in tandem with the volume ratio VR/VL, exhibiting a linear correlation with the Pearson correlation coefficient being 0.93.ConclusionThe differences in the blood distributions are consistent with the clinicians’ knowledge and validate our simulations. We demonstrated a linear increase in PV pressure with elevated SV blood velocity. Additionally, the volumes of the left and right hepatic lobes exhibited a positive correlation with blood flow rates in the corresponding PV branches.
Phase I study of the pharmacokinetics and safety of rezafungin in subjects with moderate/severe hepatic impairment and matched control subjects
Authors: Flanagan Shawn , Ong Voon , Marbury Thomas , Jandourek Alena , Gandhi Ronak G. , Sandison Taylor 
Published: June 2024

AbstractIntroductionRezafungin is a second‐generation, once‐weekly echinocandin antifungal approved for the treatment of invasive candidiasis, including candidemia. In phase II/III studies of rezafungin versus caspofungin, patients with severe hepatic impairment were excluded due to lack of caspofungin data in this population. This open‐label, single‐dose, phase I study evaluated the pharmacokinetics (primary objective) and safety of rezafungin in subjects with moderate or severe hepatic impairment versus matched, healthy subjects with normal hepatic function.MethodsEight subjects each with moderate (Child‐Pugh B) or severe (Child‐Pugh C) hepatic impairment were matched 1:1 with healthy subjects for age, sex, and body mass index. Each subject received a single 400‐mg, intravenous, 1‐h infusion of rezafungin. Plasma pharmacokinetic sampling was performed at various time points through 336 h postdose. Pharmacokinetic parameters were derived by non‐compartmental analysis. Safety was assessed throughout.ResultsAll 32 subjects received study treatment and were included in all analyses. Despite overlapping distributions of total plasma concentrations, based on geometric least‐squares (LS) mean ratios, the area under the plasma concentration–time curve from time zero (prior to the start of infusion) to infinity (AUC0–∞) was 32% lower in subjects with moderate (LS mean ratio, 67.55; 90% confidence interval [CI]: 53.91, 84.65) and severe (LS mean ratio, 67.84; 90% CI: 57.49, 80.05) hepatic impairment versus matched healthy subjects. The maximum plasma concentration (Cmax) was 12% lower in moderate hepatic impairment and 28% lower in severe hepatic impairment groups. Linear regression showed no significant trend in the degree of hepatic impairment (based on Child‐Pugh score) on AUC0–∞ or Cmax (p > 0.05). Treatment‐emergent adverse events were reported in seven subjects (21.9%; three subjects in each of the hepatic impairment groups, and one healthy subject), none of which were severe, serious, or resulted in withdrawal.ConclusionsRezafungin is well tolerated and can be administered to patients with moderate or severe hepatic impairment without the need for dose adjustment. The modest reduction in exposures in subjects with hepatic impairment is not clinically meaningful and is unlikely to impact efficacy.
On energy and particle production in cosmology: the particular case of the gravitino
Authors: Casagrande Gabriele , Dudas Emilian , Peloso Marco 
Published: June 2024

Abstract
It is well-known that the number of particles produced in cosmology, commonly defined in the literature from the Fock space of the instantaneous hamiltonian of the canonically normalized fields, is ambiguous. On the other hand, the energy computed from the energy-momentum tensor should be physical. We compare the corresponding Fock spaces and relate them through a Bogolyubov transformation. We find that for particles of spin 0, 1 and 3/2 the two Fock spaces are different, whereas they are the same for spin 1/2 fermions. For spin 0 and 1, for particles of high momenta the two Fock spaces align, as intuitively expected. For the spin 3/2, one finds two puzzles. The first one is that the two corresponding Fock spaces do not match even in the limit of high momenta. The second is that whereas we provide evidence for the equivalence theorem between longitudinal gravitinos and the goldstino in terms of an exact matching between the lagrangians and the instantaneous hamiltonians for the canonically normalized fields, the energy operator computed from the Rarita-Schwinger action does not seem to be captured in a simple way by the goldstino action. Our results suggest a re-analysis of non-thermal gravitino production in cosmology.
Seeing more than the Tip of the Iceberg: Approaches to Subthreshold Effects in Functional Magnetic Resonance Imaging of the Brain
Authors: Sundermann Benedikt , Pfleiderer Bettina , McLeod Anke , Mathys Christian 
Published: June 2024

AbstractMany functional magnetic resonance imaging (fMRI) studies and presurgical mapping applications rely on mass-univariate inference with subsequent multiple comparison correction. Statistical results are frequently visualized as thresholded statistical maps. This approach has inherent limitations including the risk of drawing overly-selective conclusions based only on selective results passing such thresholds. This article gives an overview of both established and newly emerging scientific approaches to supplement such conventional analyses by incorporating information about subthreshold effects with the aim to improve interpretation of findings or leverage a wider array of information. Topics covered include neuroimaging data visualization, p-value histogram analysis and the related Higher Criticism approach for detecting rare and weak effects. Further examples from multivariate analyses and dedicated Bayesian approaches are provided.
3D large-scale forward modeling of gravitational fields using triangular spherical prisms with polynomial densities in depth
Authors: Ouyang Fang , Chen Long-wei , Wu Leyuan 
Published: June 2024

AbstractTo take the sphericity of the Earth into account, tesseroids are often utilized as grid elements in large-scale gravitational forward modeling. However, such elements in a latitude–longitude mesh suffer from degenerating into poorly shaped triangles near poles. Moreover, tesseroids have limited flexibility in describing laterally variable density distributions with irregular boundaries and also face difficulties in achieving completely equivalent division over a spherical surface that may be desired in a gravity inversion. We develop a new method based on triangular spherical prisms (TSPs) for 3D gravitational modeling in spherical coordinates. A TSP is defined by two spherical surfaces of triangular shape, with one of which being the radial projection of the other. Due to the spherical triangular shapes of the upper and lower surfaces, TSPs enjoy more advantages over tesseroids in describing mass density with different lateral resolutions. In addition, such an element also allows subdivisions with nearly equal weights in spherical coordinates. To calculate the gravitational effects of a TSP, we assume the density in each element to be polynomial along radial direction so as to accommodate a complex density environment. Then, we solve the Newton’s volume integral using a mixed Gaussian quadrature method, in which the surface integral over the spherical triangle is calculated using a triangle-based Gaussian quadrature rule via a radial projection that transforms the spherical triangles into linear ones. A 2D adaptive discretization strategy and an extension technique are also combined to improve the accuracy at observation points near the mass sources. The numerical experiments based on spherical shell models show that the proposed method achieves good accuracy from near surface to a satellite height in the case of TSPs with various dimensions and density variations. In comparison with the classical tesseroid-based method, the proposed algorithm enjoys better accuracy and much higher flexibility for density models with laterally irregular shapes. It shows that to achieve the same accuracy, the number of elements required by the proposed method is much less than that of the tesseroid-based method, which substantially speeds up the calculation by more than 2 orders. The application to the tessellated LITHO1.0 model further demonstrates its capability and practicability in realistic situations. The new method offers an attractive tool for gravity forward and inverse problems where the irregular grids are involved.
Incidence of diabetic retinopathy in anti-tnf treated rheumatic disease patients with type 2 diabetes
Authors: Baytaroğlu İffet Merve Uçar , Baytaroğlu Ata , Toros Merve Uçar , Daldal Hatice 
Published: June 2024

Abstract
Objective
This study aimed to evaluate the impact of anti-TNF (biological) therapies on the incidence and progression of diabetic retinopathy.

Materials and methods
A cross-sectional analysis of 50 diabetic patients with rheumatic diseases (group 1) was performed. An age-, sex-, and HbA1c-matched control group (group 2) was formed from a pool of diabetic patients who underwent regular eye examinations. The presence or absence of diabetic retinopathy was also assessed. Comorbidities such as hypertension, coronary artery disease, and hyperlipidemia were also evaluated as possible confounding factors.

Results
Hundred eyes of 50 patients were evaluated in each group. Only three patients in group 1 had non-proliferative retinopathy. The median duration of rheumatic disease was 9 years, whereas that of diabetes was 11 years. The mean duration of anti-TNF therapy was 4 years. In the control group of diabetes-only patients, 13 patients developed some form of newly diagnosed diabetic retinopathy during the last five years. The calculated retinopathy occurrence between the groups was statistically significant (p < 0.05). In this study, the incidence rate ratio for patients receiving anti-TNF treatment was calculated as 0.4 in the study.

Conclusion
TNF inhibitors, with their anti-inflammatory effects, positively impact diabetic complications by reducing the incidence of retinopathy. To our knowledge, this is the first study to evaluate retinopathy development after anti-TNF therapy.
AI-driven discovery of blood xenobiotic biomarkers in neovascular age-related macular degeneration using iterative random forests
Authors: Künzel Steffen E. , Frentzel Dominik P. , Flesch Leonie T. M. , Knecht Vitus A. , Rübsam Anne , Dreher Felix , Schütte Moritz , Dubrac Alexandre , Lange Bodo , Yaspo Marie-Laure , Lehrach Hans , Joussen Antonia M. , Zeitz Oliver 
Published: June 2024

Abstract
Purpose
To investigate the xenobiotic profiles of patients with neovascular age-related macular degeneration (nAMD) undergoing anti-vascular endothelial growth factor (anti-VEGF) intravitreal therapy (IVT) to identify biomarkers indicative of clinical phenotypes through advanced AI methodologies.

Methods
In this cross-sectional observational study, we analyzed 156 peripheral blood xenobiotic features in a cohort of 46 nAMD patients stratified by choroidal neovascularization (CNV) control under anti-VEGF IVT. We employed Liquid Chromatography—Tandem Mass Spectrometry (LC–MS/MS) for measurement and leveraged an AI-driven iterative Random Forests (iRF) approach for robust pattern recognition and feature selection, aligning molecular profiles with clinical phenotypes.

Results
AI-augmented iRF models effectively refined the metabolite spectrum by discarding non-predictive elements. Perfluorooctanesulfonate (PFOS) and Ethyl β-glucopyranoside were identified as significant biomarkers through this process, associated with various clinically relevant phenotypes. Unlike single metabolite classes, drug metabolites were distinctly correlated with subretinal fluid presence.

Conclusions
This study underscores the enhanced capability of AI, particularly iRF, in dissecting complex metabolomic data to elucidate the xenobiotic landscape of nAMD and environmental impact on the disease. The preliminary biomarkers discovered offer promising directions for personalized treatment strategies, although further validation in broader cohorts is essential for clinical application.