bluuebunny/crossref_metadata_2025 huggingface dataset:
Developing Cardiothoracic Surgical Critical Care Intensivists: A Case for Distinct Training
Authors: Kopanczyk Rafal , Long Micah T. , Satyapriya Sree V. , Bhatt Amar M. , Lyaker Michael
Published: December 2022

Cardiothoracic surgical critical care medicine is practiced by a diverse group of physicians including surgeons, anesthesiologists, pulmonologists, and cardiologists. With a wide array of specialties involved, the training of cardiothoracic surgical intensivists lacks standardization, creating significant variation in practice. Additionally, it results in siloed physicians who are less likely to collaborate and advocate for the cardiothoracic surgical critical care subspeciality. Moreover, the current model creates credentialing dilemmas, as experienced by some cardiothoracic surgeons. Through the lens of critical care anesthesiologists, this article addresses the shortcomings of the contemporary cardiothoracic surgical intensivist training standards. First, we describe the present state of practice, summarize past initiatives concerning specific training, outline why standardized education is needed, provide goals of such training standardization, and offer a list of desirable competencies that a trainee should develop to become a successful cardiothoracic surgical intensivist.
A Review of Neovascular Glaucoma: Etiology, Pathogenesis, Diagnosis, and Treatment
Authors: Urbonavičiūtė Danielė , Buteikienė Dovilė , Janulevičienė Ingrida
Published: December 2022

Neovascular glaucoma (NVG) is a rare, aggressive, blinding secondary glaucoma, which is characterized by neovascularization of the anterior segment of the eye and leading to elevation of the intraocular pressure (IOP). The main etiological factor is retinal ischemia leading to an impaired homeostatic balance between the angiogenic and antiangiogenic factors. High concentrations of vasogenic substances such as vascular endothelial growth factor (VEGF) induce neovascularization of the iris (NVI) and neovascularization of the angle (NVA) that limits the outflow of aqueous humor from the anterior chamber and increases the IOP. NVG clinical, if untreated, progresses from secondary open-angle glaucoma to angle-closure glaucoma, leading to irreversible blindness. It is an urgent ophthalmic condition; early diagnosis and treatment are necessary to preserve vision and prevent eye loss. The management of NVG requires the cooperation of retinal and glaucoma specialists. The treatment of NVG includes both control of the underlying disease and management of IOP. The main goal is the prevention of angle-closure glaucoma by combining panretinal photocoagulation (PRP) and antiangiogenic therapy. The aim of this review is to summarize the current available knowledge about the etiology, pathogenesis, and symptoms of NVG and determine the most effective treatment methods.
An Overview of the Modification Strategies in Developing Antifouling Nanofiltration Membranes
Authors: Ahmad Nor Naimah Rosyadah , Mohammad Abdul Wahab , Mahmoudi Ebrahim , Ang Wei Lun , Leo Choe Peng , Teow Yeit Haan
Published: December 2022

Freshwater deficiency has become a significant issue affecting many nations’ social and economic development because of the fast-growing demand for water resources. Nanofiltration (NF) is one of the promising technologies for water reclamation application, particularly in desalination, water, and wastewater treatment fields. Nevertheless, membrane fouling remains a significant concern since it can reduce the NF membrane performance and increase operating expenses. Consequently, numerous studies have focused on improving the NF membrane’s resistance to fouling. This review highlights the recent progress in NF modification strategies using three types of antifouling modifiers, i.e., nanoparticles, polymers, and composite polymer/nanoparticles. The correlation between antifouling performance and membrane properties such as hydrophilicity, surface chemistry, surface charge, and morphology are discussed. The challenges and perspectives regarding antifouling modifiers and modification strategies conclude this review.
Polyhexanide-Releasing Membranes for Antimicrobial Wound Dressings: A Critical Review
Authors: Guiomar António Jorge , Urbano Ana M.
Published: December 2022

The prevalence of chronic, non-healing skin wounds in the general population, most notably diabetic foot ulcers, venous leg ulcers and pressure ulcers, is approximately 2% and is expected to increase, driven mostly by the aging population and the steady rise in obesity and diabetes. Non-healing wounds often become infected, increasing the risk of life-threatening complications, which poses a significant socioeconomic burden. Aiming at the improved management of infected wounds, a variety of wound dressings that incorporate antimicrobials (AMDs), namely polyhexanide (poly(hexamethylene biguanide); PHMB), have been introduced in the wound-care market. However, many wound-care professionals agree that none of these wound dressings show comprehensive or optimal antimicrobial activity. This manuscript summarizes and discusses studies on PHMB-releasing membranes (PRMs) for wound dressings, detailing their preparation, physical properties that are relevant to the context of AMDs, drug loading and release, antibacterial activity, biocompatibility, wound-healing capacity, and clinical trials conducted. Some of these PRMs were able to improve wound healing in in vivo models, with no associated cytotoxicity, but significant differences in study design make it difficult to compare overall efficacies. It is hoped that this review, which includes, whenever available, international standards for testing AMDs, will provide a framework for future studies.
A Thermodynamic Study on the Interaction between RH-23 Peptide and DMPC-Based Biomembrane Models
Authors: Giordani Cristiano , Russo Stefano , Torrisi Cristina , Morante Silvia , Castelli Francesco , Sarpietro Maria Grazia
Published: December 2022

Investigation of the interaction between drugs and biomembrane models, as a strategy to study and eventually improve drug/substrate interactions, is a crucial factor in preliminary screening. Synthesized peptides represent a source of potential anticancer and theragnostic drugs. In this study, we investigated the interaction of a novel synthesized peptide, called RH-23, with a simplified dimyristoylphosphatidylcholine (DMPC) model of the cellular membrane. The interaction of RH-23 with DMPC, organized either in multilamellar vesicles (MLVs) and in Langmuir-Blodgett (LB) monolayers, was assessed using thermodynamic techniques, namely differential scanning calorimetry (DSC) and LB. The calorimetric evaluations showed that RH-23 inserted into MLVs, causing a stabilization of the phospholipid gel phase that increased with the molar fraction of RH-23. Interplay with LB monolayers revealed that RH-23 interacted with DMPC molecules. This work represents the first experimental thermodynamic study on the interaction between RH-23 and a simplified model of the lipid membrane, thus providing a basis for further evaluations of the effect of RH-23 on biological membranes and its therapeutic/diagnostic potential.
Modeling the Conductivity and Diffusion Permeability of a Track-Etched Membrane Taking into Account a Loose Layer
Authors: Nichka Vladlen S. , Mareev Semyon A. , Apel Pavel Yu. , Sabbatovskiy Konstantin G. , Sobolev Vladimir D. , Nikonenko Victor V.
Published: December 2022

The microheterogeneous model makes it possible to describe the main transport properties of ion-exchange membranes using a single set of input parameters. This paper describes an adaptation of the microheterogeneous model for describing the electrical conductivity and diffusion permeability of a track-etched membrane (TEM). Usually, the transport parameters of TEMs are evaluated assuming that ion transfer occurs through the solution filling the membrane pores, which are cylindrical and oriented normally to the membrane surface. The version of the microheterogeneous model developed in this paper takes into account the presence of a loose layer, which forms as an intermediate layer between the pore solution and the membrane bulk material during track etching. It is assumed that this layer can be considered as a “gel phase” in the framework of the microheterogeneous model due to the fixed hydroxyl and carboxyl groups, which imparts ion exchange properties to the loose layer. The qualitative and quantitative agreement between the calculated and experimental concentration dependencies of the conductivity and diffusion permeability is discussed. The role of the model input parameters is described in relation to the structural features of the membrane. In particular, the inclination of the pores relative to the surface and their narrowing in the middle part of the membrane can be important for their properties.
Self-Diffusion Coefficients of Components in Liquid Binary Alloys of Noble Metals
Authors: Dubinin Nikolay , Ryltsev Roman
Published: December 2022

An accurate determination of transport coefficients in liquids, such as diffusivity, is crucial for studying fundamental chemical processes, for constructing and verifying model theories of liquid, and for the optimization of technological processes. However, a reliable experimental determination of the diffusivity is a difficult and sometimes nearly impossible task. In this regard, the development of model theories that allow calculating characteristics of atomic transport is of special interest. Here, the concentration dependencies of the self-diffusion coefficients of the components in Cu-Ag, Cu-Au, and Ag-Au liquid alloys at T = 1423 K and T = 1573 K are calculated in the framework of the linear trajectory approximation in conjunction with the square-well model and the semi-analytical representation of the mean spherical approximation. We reveal that peculiarities in the behavior of the obtained dependencies are related to the peculiarities of the phase diagrams of the alloys under consideration. Additionally, we verify our calculation method on Al80-Cu20 and Al80-Au20 liquid alloys. The results obtained are in good agreement with available experimental and molecular-dynamic simulation data. In the cases when the experimental information is not available, the presented results can be considered as predictive to estimate the quantities under consideration approximately.
The Effect of MC-Type Carbides on the Microstructure and Wear Behavior of S390 High-Speed Steel Produced via Spark Plasma Sintering
Authors: Hu Qipeng , Wang Miaohui , Chen Yunbo , Liu Hailong , Si Zhen
Published: December 2022

The microstructure and wear behavior of S390 high-speed steel (HSS) reinforced with different volume fractions of MC-type carbides produced via spark plasma sintering were investigated using scanning electron microscopy (SEM) and transmission electron microscopy (TEM) in this study. SEM and TEM results show that V-W-rich carbides are formed around the added MC-type carbides, and these carbides have a similar composition to the M(C, N) carbides precipitated at high temperatures according to thermodynamic calculations. Both macrohardness and three-point bending results show that the carbide type is the dominant factor increasing the hardness, and the volume fraction of the carbide is the dominant factor leading to a decrease in the three-point bending strength. The wear mechanism of HSS metal matrix composites (MMCs) is confirmed as abrasive wear and oxidative wear via wear tracks and oxidation films. Compared with the sample without reinforcement (85 HRA, wear coefficient of 1.50 × 10−15 m2/N), the best MT-3 sample exhibits a hardness increase of 1.8 HRA and a three-fold increase in wear resistance.
Mechanical Properties Evolution of the 7B04-T74 Aluminum Alloy in the Marine Atmosphere
Authors: Li Ning , Yan Xiaojun , Liu Xuerong , Han Lu , Zhang Weifang
Published: December 2022

The 7xxx-series aluminum alloys are widely used in aircrafts due to their superior performance. The evolution of the mechanical properties of the aluminum alloys caused by marine atmospheric corrosion has become a research hotspot due to the increase in aircraft service time in the marine atmospheric environment. In this work, the evolution of the mechanical properties of the 7B04-T74 aluminum alloy was studied by an alternate immersion test. The surface microstructure was analyzed by SEM, EDS, XRD, and OM. The influence of the marine atmospheric corrosion on mechanical properties was studied by tensile and fatigue tests. The results show that the 7B04-T74 aluminum alloy has good corrosion resistance, as only pitting corrosion occurs in the marine atmospheric environment. The tensile properties of the 7B04-T74 aluminum alloy remained fundamentally the same before and after corrosion. The fatigue properties of the 7B04-T74 aluminum alloy were severely reduced, but the localized pitting corrosion only affected the initiation stage of the crack and had little effect on the crack propagation process.
Effects of Heat Treatment on the Microstructure and Properties of a Cast Nickel-Based High-Cr Superalloy
Authors: Lu Hongguo , Yang Minghui , Zhou Li , Ma Zhonggang , Cui Bin , Yin Fengshi , Li Daoqian
Published: December 2022

The effect of solution treatment and intermediate heat treatment on the microstructure and properties of a new cast nickel-based high-Cr superalloy was investigated in this paper. The results indicate that the tensile strength and elongation at 900 °C increase when the solution temperature increases from 1160 °C to 1180 °C and then decrease when the solution temperature changes from 1180 °C to 1200 °C and 1220 °C. The stress rupture test results of the high-Cr superalloy under conditions of 900 °C/275 MPa shows that the rupture time, elongation, and reduction of area initially increased and then decreased with the increase in solution treatment temperatures. The results of stress rupture tests for the alloy after intermediate heat treatment followed by furnace-cooling, air-cooling, and water-cooling show that the morphology and distribution of γ’ phase have a great influence on the tensile test results at 900 °C of the alloy but no obvious influence on the test at 900 °C/275 MPa. The microstructure analysis of the superalloy after heat treatment shows that: when the solution treatment temperatures are at 1200 °C and 1220 °C, the incipient melting appears in the interdendritic region, which can severely deteriorate mechanical properties; the morphology of γ′ phase changes gradually from cube to spherical; and a large number of fine γ’ phase precipitates in the γ channel are found with increasing cooling rate after intermediate heat treatment.
Tempering Behavior of Novel Low-Alloy High-Strength Steel
Authors: Dudko Valeriy , Yuzbekova Diana , Gaidar Sergey , Vetrova Sofia , Kaibyshev Rustam
Published: December 2022

The effect of tempering on the mechanical properties, structure, and dispersion of secondary phase particles is studied in 0.4%C-2%Si-1%Cr-1%Mo-VNb steel. This steel austenitized at 900 °C with subsequent water quenching exhibits a yield stress of 1445 MPa and a lath martensite structure with MX particles of ~40 nm located in matrix and boundary M6C carbides of ~210 nm. Tempering in the temperature interval of 200–400 °C provides a yield stress of 1625 MPa due to the precipitation of ε-carbide and cementite within laths. The yield stress decreases to 1415 and 1310 MPa after tempering at 500 and 650 °C, respectively, due to the replacement of matrix carbides by boundary M23C6 carbide. A Charpy V-notch impact energy of ~12 J/cm2 is almost independent from tempering temperatures of up to 400 °C and increases up to ~33 J/cm2 after tempering at 650 °C due to decreased yield stresses and increased plasticity.
Experimental Study of the Microhardness and Microstructure of a Copper Specimen Using the Taylor Impact Test
Authors: Zelepugin Sergey A. , Pakhnutova Nadezhda V. , Shkoda Olga A. , Boyangin Evgenii N.
Published: December 2022

One commonly used method for characterizing the dynamic characteristics of materials is the Taylor impact test. This method measures the dynamic yield strength of cylindrical specimens and determines material model constants required for the numerical simulation of the behavior of materials subjected to high-velocity deformation. The purpose of this work is to investigate the microhardness and microstructure of copper specimens at different impact velocities using the Taylor impact test. This paper describes experiments performed on copper specimens (OFHC 99.9%, M1) using a single-stage light-gas gun with impact velocities in the range of 150–450 m/s. After impact, the specimens were cut along the symmetry axis to measure the microhardness and the grain size of the microstructure. Microhardness in the entire area exceeded the initial value for all investigated velocities. The averaged microhardness curves were obtained for each specimen to identify four deformation zones and determine their dimensions depending on the impact velocity. The average grain size in the entire deformed specimen became smaller than in the starting specimen. The study of the microstructure of the specimens has shown that the grain size distribution corresponds to the four deformation zones in the copper specimens.
Influence of Heat Treatment and Deformation on the Structure, Phase Transformation, and Mechanical Behavior of Bulk TiNi-Based Alloys
Authors: Kuranova Nataliya N. , Makarov Vladimir V. , Pushin Vladimir G. , Ustyugov Yurii M.
Published: December 2022

We present a brief overview of the structural and phase transformations and mechanical properties of bulk binary TiNi shape memory alloys, which demonstrate attractive commercial potential. The main goal of this work was to create a favorable microstructure of bulk alloys using both traditional and new alternative methods of thermal and thermomechanical processing. It was found that the implementation of an ultrafine-grained structure by different methods determined an unusual combination of strength, ductility, reversible deformation, reactive resistance of these alloys to subsequent tensile or torsion tests at room temperature, and, as a consequence, the highly reversible effects of the shape memory and superelasticity. It is shown that the alloys Ti49.8Ni50.2 and Ti49.4Ni50.6 are incapable of aging, and, after being subjected to ECAP, were characterized by their high strength (σu up to 1200 MPa) and ductility (δ up to 60–70%). A combined treatment of multi-pass rolling and HT of the Ti49.5Ni50.5 and Ti49Ni51 alloys prone to aging have provided even greater strength (σu up to 1400–1500 MPa) with slightly lower ductility (25–30%). The microstructure, phase composition, and martensitic transformations in Ti-Ni alloys with varying Ni concentrations ranging from 50 to 51 wt.% were investigated by TEM, SEM, and X-ray methods. The mechanical behavior of the alloys was studied during tensile and torsion tests.
The Effect of Heat Treatment and Different Degrees of Deformation on the Microstructure and Mechanical Properties of Pure Mo Sheets
Authors: Chen Wenjing , Gu Lina , Han Jiayu , Ge Songwei , Hua Xingjiang , Hu Ping , Bai Run , Zhang Wen , Chang Tian , Wang Kuaishe
Published: December 2022

Molybdenum has a broad application and good prospect in the field of nuclear energy, aerospace, electronics, etc., due to its high melting point, high hardness, corrosion resistance and other excellent performances. In this paper, an isothermal and isochronous annealing heat treatment, at the temperature of 800–1300 °C for 0.5–2 h, was applied to pure molybdenum (PM) sheets with deformation of 70%, 80%, 90%, and 95%. The initial deformation of the PM sheet was increased from 70% to 95%. After annealing at 900–1200 °C for 1 h, the recrystallized grain size gradually decreased. The Goss texture ({110}<001>) was always present in the pure molybdenum sheet with 95% deformation during heat treatment, but its strength decreased with the increase of the temperature. The copper texture ({112}<110>) deflected to a cubic texture, and its orientation changed from {001}<110> to that of cube texture {110}<100>. With the increase of the temperature, the cubic texture was obtained more easily in the pure molybdenum sheet. The recrystallization nucleation mechanism of the pure molybdenum sheet with 95% deformation was mainly in situ nucleation and orientation nucleation. The Avrami index of the pure molybdenum sheet with 95% deformation was calculated by the JMAK equation and found to be 3.6.
ConCISE: Consensus Annotation Propagation of Ion Features in Untargeted Tandem Mass Spectrometry Combining Molecular Networking and In Silico Metabolite Structure Prediction
Authors: Quinlan Zachary A. , Koester Irina , Aron Allegra T. , Petras Daniel , Aluwihare Lihini I. , Dorrestein Pieter C. , Nelson Craig E. , Wegley Kelly Linda
Published: December 2022

Recent developments in molecular networking have expanded our ability to characterize the metabolome of diverse samples that contain a significant proportion of ion features with no mass spectral match to known compounds. Manual and tool-assisted natural annotation propagation is readily used to classify molecular networks; however, currently no annotation propagation tools leverage consensus confidence strategies enabled by hierarchical chemical ontologies or enable the use of new in silico tools without significant modification. Herein we present ConCISE (Consensus Classifications of In Silico Elucidations) which is the first tool to fuse molecular networking, spectral library matching and in silico class predictions to establish accurate putative classifications for entire subnetworks. By limiting annotation propagation to only structural classes which are identical for the majority of ion features within a subnetwork, ConCISE maintains a true positive rate greater than 95% across all levels of the ChemOnt hierarchical ontology used by the ClassyFire annotation software (superclass, class, subclass). The ConCISE framework expanded the proportion of reliable and consistent ion feature annotation up to 76%, allowing for improved assessment of the chemo-diversity of dissolved organic matter pools from three complex marine metabolomics datasets comprising dominant reef primary producers, five species of the diatom genus Pseudo-nitzchia, and stromatolite sediment samples.
Identification of a Chromosome 1 Substitution Line B6-Chr1BLD as a Novel Hyperlipidemia Model via Phenotyping Screening
Authors: Li Xu , Sun Minli , Qi Hao , Ju Cunxiang , Chen Zhong , Gao Xiang , Lin Zhaoyu
Published: December 2022

Hyperlipidemia is a chronic disease that seriously affects human health. Due to the fact that traditional animal models cannot fully mimic hyperlipidemia in humans, new animal models are urgently needed for basic drug research on hyperlipidemia. Previous studies have demonstrated that the genomic diversity of the wild mice chromosome 1 substitution lines was significantly different from that of laboratory mice, suggesting that it might be accompanied by phenotypic diversity. We first screened the blood lipid-related phenotype of chromosome 1 substitution lines. We found that the male HFD-fed B6-Chr1BLD mice showed more severe hyperlipidemia-related phenotypes in body weight, lipid metabolism and liver lesions. By RNA sequencing and whole-genome sequencing results of B6-Chr1BLD, we found that several differentially expressed single nucleotide polymorphism enriched genes were associated with lipid metabolism-related pathways. Lipid metabolism-related genes, mainly including Aida, Soat1, Scly and Ildr2, might play an initial and upstream role in the abnormal metabolic phenotype of male B6-Chr1BLD mice. Taken together, male B6-Chr1BLD mice could serve as a novel, polygenic interaction-based hyperlipidemia model. This study could provide a novel animal model for accurate clinical diagnosis and precise medicine of hyperlipidemia.
Parameters of Vitamin D Metabolism in Patients with Hypoparathyroidism
Authors: Zhukov Artem , Povaliaeva Alexandra , Abilov Zaur , Kovaleva Elena , Usoltseva Liliya , Eremkina Anna , Ioutsi Vitaliy , Dzeranova Larisa , Pigarova Ekaterina , Rozhinskaya Liudmila , Mokrysheva Natalia
Published: December 2022

Only a few studies evaluating the metabolism of vitamin D in patients with hypoparathyroidism (HypoPT) have been performed thus far, and, in particular, they mainly investigated the process of vitamin D activation (specifically, 1α-hydroxylation). This study, therefore, aimed to evaluate the extended spectrum of vitamin D metabolites in patients with HypoPT compared to healthy individuals. We examined 38 adult patients with chronic HypoPT in comparison to 38 healthy adults. The assessment included biochemical parameters (total calcium, albumin, phosphorus, creatinine, and magnesium), parathyroid hormone (PTH), and vitamin D metabolites (25(OH)D3, 25(OH)D2, 1,25(OH)2D3, 3-epi-25(OH)D3, and 24,25(OH)2D3) in serum. Our data show that an adequate level of 25(OH)D3 (median 35.3 (29.6; 42.0) ng/mL) is achieved with standard doses of cholecalciferol (median 2000 (2000; 2500) IU per day) in HypoPT patients. They also presented with supraphysiological levels of 1,25(OH)2D3 (median 71 (47; 96) vs. 40 (34; 59) pg/mL, p < 0.001) and the increased production of inactive metabolite (median 24,25(OH)2D3 3.8 (3.0; 5.1) vs. 1.9 (1.3; 2.7) ng/mL, p < 0.001; median 25(OH)D3/24,25(OH)2D3 ratio 8.9 (7.6; 11.1) vs. 13.5 (11.1; 17.0), p < 0.001) as compared to the control group. This might be a consequence of the therapy received (treatment with activated vitamin D) and the pathophysiology of the disease (lack of PTH). The abnormality of vitamin D metabolism does not seem to interfere with the achievement of hypoparathyroidism compensation.
Lipid Alterations in Glioma: A Systematic Review
Authors: Abdul Rashid Khairunnisa , Ibrahim Kamariah , Wong Jeannie Hsiu Ding , Mohd Ramli Norlisah
Published: December 2022

Gliomas are highly lethal tumours characterised by heterogeneous molecular features, producing various metabolic phenotypes leading to therapeutic resistance. Lipid metabolism reprogramming is predominant and has contributed to the metabolic plasticity in glioma. This systematic review aims to discover lipids alteration and their biological roles in glioma and the identification of potential lipids biomarker. This systematic review was conducted using the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Extensive research articles search for the last 10 years, from 2011 to 2021, were conducted using four electronic databases, including PubMed, Web of Science, CINAHL and ScienceDirect. A total of 158 research articles were included in this study. All studies reported significant lipid alteration between glioma and control groups, impacting glioma cell growth, proliferation, drug resistance, patients’ survival and metastasis. Different lipids demonstrated different biological roles, either beneficial or detrimental effects on glioma. Notably, prostaglandin (PGE2), triacylglycerol (TG), phosphatidylcholine (PC), and sphingosine-1-phosphate play significant roles in glioma development. Conversely, the most prominent anti-carcinogenic lipids include docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and vitamin D3 have been reported to have detrimental effects on glioma cells. Furthermore, high lipid signals were detected at 0.9 and 1.3 ppm in high-grade glioma relative to low-grade glioma. This evidence shows that lipid metabolisms were significantly dysregulated in glioma. Concurrent with this knowledge, the discovery of specific lipid classes altered in glioma will accelerate the development of potential lipid biomarkers and enhance future glioma therapeutics.
Optimising Fluvoxamine Maternal/Fetal Exposure during Gestation: A Pharmacokinetic Virtual Clinical Trials Study
Authors: Burhanuddin Khairulanwar , Badhan Raj
Published: December 2022

Fluvoxamine plasma concentrations have been shown to decrease throughout pregnancy. CYP2D6 polymorphisms significantly influence these changes. However, knowledge of an optimum dose adjustment according to the CYP2D6 phenotype is still limited. This study implemented a physiologically based pharmacokinetic modelling approach to assess the gestational changes in fluvoxamine maternal and umbilical cord concentrations. The optimal dosing strategies during pregnancy were simulated, and the impact of CYP2D6 phenotypes on fluvoxamine maternal and fetal concentrations was considered. A significant decrease in fluvoxamine maternal plasma concentrations was noted during gestation. As for the fetal concentration, a substantial increase was noted for the poor metabolisers (PM), with a constant level in the ultrarapid (UM) and extensive (EM) metabolisers commencing from gestation week 20 to term. The optimum dosing regimen suggested for UM and EM reached a maximum dose of 300 mg daily at gestational weeks (GW) 15 and 35, respectively. In contrast, a stable dose of 100 mg daily throughout gestation for the PM is sufficient to maintain the fluvoxamine plasma concentration within the therapeutic window (60–230 ng/mL). Dose adjustment during pregnancy is required for fluvoxamine, particularly for UM and EM, to maintain efficacy throughout the gestational period.
Urinary Metabolomics in Young Soccer Players after Winter Training Season
Authors: Kim Hyang-Yeon , Lee Jung-Dae , Lee Yun-Hwan , Seo Sang-Won , Lee Ho-Seong , Kim Suhkmann , Kim Kyu-Bong
Published: December 2022

During the off-season, soccer players in Korea attend the winter training season (WTS) to build running stamina for the next season. For young soccer players, proper recovery time is needed to prevent injury or muscle damage. In this study, urinary metabolites in young players after 1, 5, and 10 days of the WTS were analyzed using nuclear magnetic resonance spectroscopy (NMR) combined with multivariate analysis to suggest appropriate recovery times for improving their soccer skills. After NMR analysis of the urine samples obtained from young players, 79 metabolites were identified, and each group (1, 5, or 10 days after WTS) was separated from the before the WTS group in the target profiling analysis using partial least squares-discriminant analysis (PLS-DA). Of these, 15 metabolites, including 1-methylnicotinamide, 3-indoxylsulfate, galactarate, glutamate, glycerol, histamine, methylmalonate, maltose, N-phenylacetylglycine, trimethylamine, urea, 2-hydroxybutyrate, adenine, alanine, and lactate, were significantly different than those from before the WTS and were mainly involved in the urea, purine nucleotide, and glucose-alanine cycles. In this study, most selected metabolites increased 1 day after the WTS and then returned to normal levels. However, 4 metabolites, adenine, 2-hydroxybutyrate, alanine, and lactate, increased during the 5 days of recovery time following the WTS. Based on excess ammonia, adenine, and lactate levels in the urine, at least 5 days of recovery time can be considered appropriate.
An Efficient and Economical N-Glycome Sample Preparation Using Acetone Precipitation
Authors: Wang Junyao , Peng Wenjing , Fowowe Mojibola , Daramola Oluwatosin , Mechref Yehia
Published: December 2022

Due to the critical role of the glycome in organisms and its close connections with various diseases, much time and effort have been dedicated to glycomics-related studies in the past decade. To achieve accurate and reliable identification and quantification of glycans extracted from biological samples, several analysis methods have been well-developed. One commonly used methodology for the sample preparation of N-glycomics usually involves enzymatic cleavage by PNGase F, followed by sample purification using C18 cartridges to remove proteins. PNGase F and C18 cartridges are very efficient both for cleaving N-glycans and for protein removal. However, this method is most suitable for a limited quantity of samples. In this study, we developed a sample preparation method focusing on N-glycome extraction and purification from large-scale biological samples using acetone precipitation. The N-glycan yield was first tested on standard glycoprotein samples, bovine fetuin and complex biological samples, and human serum. Compared to C18 cartridges, most of the sialylated N-glycans from human serum were detected with higher abundance after acetone precipitation. However, C18 showed a slightly higher efficiency for protein removal. Using the unfiltered human serum as the baseline, around 97.7% of the proteins were removed by acetone precipitation, while more than 99.9% of the proteins were removed by C18 cartridges. Lastly, the acetone precipitation was applied to N-glycome extraction from egg yolks to demonstrate large-scale glycomics sample preparation.
Efficacy of Different Modalities and Frequencies of Physical Exercise on Glucose Control in People with Prediabetes (GLYCEX Randomised Trial)
Authors: Galmes-Panades Aina M , Bennasar-Veny Miquel , Oliver Paula , Garcia-Coll Natalia , Chaplin Alice , Fresneda Sergio , Gallardo-Alfaro Laura , García-Ruano Carmen , Konieczna Jadwiga , Leiva Alfonso , Masmiquel Lluis , Pico Catalina , Ricci-Cabello Ignacio , Romaguera Dora , Rivera Rosmeri , Sanchis Pilar , Vidal-Conti Josep , Yañez Aina M
Published: December 2022

To assess the efficacy of different modalities and frequencies of physical exercise on glycaemic control in adults with prediabetes. A two-phase, parallel, randomised, controlled clinical trial will be carried out, in 210 participants. In phase 1, 120 participants will be randomized into four arms: (1) aerobic exercise, (2) aerobic exercise combined with resistance, (3) high-intensity intervallic exercise and (4) control group. In phase 2, 90 new participants will be randomized into three arms, using the exercise modality that showed the best glycaemic control in phase 1 in the following manner: (1) frequency of 5 days/week, (2) frequency of 3 days/week and (3) frequency of 2 days/week. The control group (n = 30) will be included in phase 1 to evaluate the effect of any type of intervention versus no intervention. Data collection will be performed at baseline and after 15 weeks of follow up. Sociodemographic data, medication, comorbidity, blood biochemical parameters, blood pressure, anthropometric measurements, body composition, physical activity, sedentary lifestyle, diet, smoking, alcohol consumption, quality of life and sleep questionnaires will be collected. Physical activity, sedentary behaviour and sleep will be further determined with an accelerometer, and continuous glycaemia will be determined with a glycaemic monitor, both during seven days, at two time points. The main dependent variable will be the reduction in the mean amplitude of glycaemic excursions. The impact of these interventions on health will also be evaluated through gene expression analysis in peripheral blood cells. The results of this study will contribute to a better understanding of the mechanisms behind the glucose response to physical exercise in a population with prediabetes as well as improve physical exercise prescriptions for diabetes prevention. Increasing glycaemic control in people with prediabetes through physical exercise offers an opportunity to prevent diabetes and reduce associated comorbidities and health costs.
Long-Term Impacts of Diurnal Temperature Range on Mortality and Cardiovascular Disease: A Nationwide Prospective Cohort Study
Authors: Tang Haosu , Wang Xin , Kang Yuting , Zheng Congyi , Cao Xue , Tian Yixin , Hu Zhen , Zhang Linfeng , Chen Zuo , Song Yuxin , Gu Runqing , Cai Jiayin , Huang Gang , Wang Zengwu
Published: December 2022

Previous studies have documented the associations between short-term diurnal temperature range (DTR) exposure and cardiovascular disease (CVD) via time-series analyses. However, the long-term impacts of DTR through a population-based prospective cohort have not been elucidated thoroughly. This study aimed to quantify the longitudinal association of DTR exposure with all-cause mortality and CVD in a nationwide prospective cohort and, by extension, project future DTR changes across China under climate change. We included 22,702 adults (median age 56.1 years, 53.7% women) free of CVD at baseline from a nationwide cross-sectional study in China during 2012–2015, and examined three health outcomes during a follow-up survey in 2018–2019. We estimated the chronic DTR exposure as baseline annual mean daily maximum minus minimum temperature. The Cox proportional hazards regression was adopted to assess the multivariable-adjusted hazard ratio and its corresponding 95% confidence interval (95% CI). We employed 31 downscaled global climate models under two shared socioeconomic pathways for future projection. During the median follow-up period of ~5 years, 1096 subjects died due to all causes while 993 and 597 individuals developed fatal or nonfatal CVD and fatal or nonfatal stroke, respectively. The cumulative incidence rates of all-cause mortality, CVD, and stroke were 10.49, 9.45, and 5.64 per 1000 person-years, respectively. In the fully adjusted models, the risks for all-cause mortality, CVD, and stroke would increase by 13% (95% CI: 8–18%), 12% (95% CI: 7–18%), and 9% (95% CI: 2–16%) per 1 °C increment in DTR, respectively. Moreover, linear positive associations for the concentration–response curves between DTR and mortality and CVD were observed. We also found significantly greater DTR-related mortality risks among rural residents than their urban counterparts. The DTR changes featured a dipole pattern across China under a warming climate. The southern (northern) China would experience increased (decreased) DTR exposure by the end of 21st century. The present study indicates that chronic DTR exposure can exert long-term impacts on mortality and CVD risks, which may inform future public health policies on DTR-related susceptible population and regions.
Metabolomic Analysis Reveals the Effect of Insecticide Chlorpyrifos on Rice Plant Metabolism
Authors: Mu Qi’er , Zhang Mingxia , Li Yong , Feng Fayun , Yu Xiangyang , Nie Jinfang
Published: December 2022

Pesticides as important agricultural inputs play a vital role in protecting crop plants from diseases and pests; however, the effect of pesticides on crop plant physiology and metabolism is still undefined. In this study, the effect of insecticide chlorpyrifos at three doses on rice plant physiology and metabolism was investigated. Our results revealed that chlorpyrifos cause oxidative stress in rice plants and even inhibit plant growth and the synthesis of protein and chlorophyll at high doses. The metabolomic results suggested that chlorpyrifos could affect the metabolic profiling of rice tissues and a total of 119 metabolites with significant changes were found, mainly including organic acids, amino acids, lipids, polyphenols, and flavonoids. Compared to the control, the content of glutamate family amino acids were significantly disturbed by chlorpyrifos, where defense-related proline and glutathione were significantly increased; however, glutamic acid, N-acetyl-glutamic acid and N-methyl-glutamic acid were significantly decreased. Many unsaturated fatty acids, such as linolenic acid and linoleic acid, and their derivatives lysophospholipids and phospholipids, were significantly accumulated in chlorpyrifos groups, which could act as osmolality substances to help rice cells relieve chlorpyrifos stress. Three organic acids, aminobenzoic acid, quinic acid, and phosphoenolpyruvic acid, involved in plant defenses, were significantly accumulated with the fold change ranging from 1.32 to 2.19. In addition, chlorpyrifos at middle- and high-doses caused the downregulation of most flavonoids. Our results not only revealed the effect of insecticide chlorpyrifos on rice metabolism, but also demonstrated the value of metabolomics in elucidating the mechanisms of plant responses to stresses.
Transcription and Metabolism Pathways of Anthocyanin in Purple Shamrock (Oxalis triangularis A.St.-Hil.)
Authors: Luo Baobing , Chen Liujun , Chen Guoping , Wang Yunshu , Xie Qiaoli , Chen Xuqing , Hu Zongli
Published: December 2022

Anthocyanins are water-soluble pigments that can impart various colors to plants. Purple shamrock (Oxalis triangularis) possesses unique ornamental value due to its purple leaves. In this study, three anthocyanins, including malvidin 3-O-(4-O-(6-O-malonyl-glucopyranoside)-rhamnopyranosyl)-5-O-(6-O-malonyl-glucopyranoside), delphinidin-3-O-rutinoside and malvidin-3,5-di-O-glucoside, were characterized with ultra-performance liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS) in purple shamrock. To investigate the molecular mechanism of anthocyanin biosynthesis in green shamrock (Oxalis corymbosa) and purple shamrock, RNA-seq and qRT-PCR were performed, and the results showed that most of the anthocyanin biosynthetic and regulatory genes were up-regulated in purple shamrock. Then, dark treatment and low temperature treatment experiments in purple shamrock showed that both light and low temperature can induce the biosynthesis of anthocyanins.
A Preliminary Pilot Study: Metabolomic Analysis of Saliva in Oral Candidiasis
Authors: Adachi Takuya , Kawanishi Norishige , Ichigaya Narumi , Sugimoto Masahiro , Hoshi Noriyuki , Kimoto Katsuhiko
Published: December 2022

Early detection of oral candidiasis is essential. However, most currently available methods are time-consuming and useful only for screening patients. Previous studies on the relationship between oral candidiasis and saliva have focused on saliva volume and not on its components. Therefore, to clarify the effects of oral candidiasis on salivary metabolites, the relationship between salivary components and oral candidiasis was investigated by comparing the salivary metabolites of oral candidiasis patients and those not previously diagnosed with candidiasis. Forty-five participants visiting our university hospital were included and classified into two groups, the Candida group and the control group, based on the Candida detection test results. The unstimulated saliva was collected using the spitting method over 15 min, and the stimulated saliva was collected using the gum-chewing method over 10 min. The saliva volume was measured, and the saliva samples were frozen and analyzed metabolomically. Metabolome analysis revealed 51 metabolites with peak detection rates exceeding 50%. There was no significant difference in age and sex between the Candida and control groups. In the Candida group, five metabolites (tyrosine, choline, phosphoenolpyruvate, histidine, and 6-phosphogluconate) were significantly elevated in the unstimulated, two (octanoic acid and uridine monophosphate(UMP)) were significantly increased, and four (ornithine, butyrate, aminovalerate and aminolevulinate) were significantly decreased in the stimulated saliva. This study suggests the possibility of identifying metabolites specific to patients with oral candidiasis, which could aid prompt diagnosis.
A Targeted and an Untargeted Metabolomics Approach to the Volatile Aroma Profile of Young ‘Maraština’ Wines
Authors: Boban Ana , Vrhovsek Urska , Carlin Silvia , Mucalo Ana , Budić-Leto Irena
Published: December 2022

This study investigated the detailed volatile aroma profile of young white wines of Maraština, Vitis Vinifera L., produced by spontaneous fermentation. The wines were produced from 10 vineyards located in two Dalmatian subregions (Northern Dalmatia and Central and Southern Dalmatia). Volatile compounds from the wine samples were isolated by solid-phase extraction (SPE) and analyzed by an untargeted approach using two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (GC×GC/TOF-MS) and a targeted approach by gas chromatography–tandem mass spectrometry (GC-MS/MS). A comprehensive two-dimensional GC×GC analysis detailed the total volatile metabolites in the wines due to its excellent separation ability. More than 900 compounds were detected after untargeted profiling; 188 of them were identified or tentatively identified. A total of 56 volatile compounds were identified and quantified using GC-MS/MS analysis. The predominant classes in Maraština wines were acids, esters, and alcohols. The key odorants with odor activity values higher than one were β-damascenone, ethyl caprylate, ethyl isovalerate, ethyl 2-methylbutyrate, ethyl caproate, isopentyl acetate, ethyl butyrate, and phenylacetaldehyde. The metabolomics approach can provide a large amount of information and can help to anticipate variation in wines or change winemaking procedures.
Integrated Analysis of Widely Targeted Metabolomics and Transcriptomics Reveals the Effects of Transcription Factor NOR-like1 on Alkaloids, Phenolic Acids, and Flavonoids in Tomato at Different Ripening Stages
Authors: Yang Xinyu , Zhao Xiaodan , Fu Daqi , Zhao Ying
Published: December 2022

Tomato is abundant in alkaloids, phenolic acids, and flavonoids; however, the effect of transcription factor NOR-like1 on these metabolites in tomato is unclear. We used a combination of widely targeted metabolomics and transcriptomics to analyze wild-type tomatoes and CR-NOR-like1 tomatoes. A total of 83 alkaloids, 85 phenolic acids, and 96 flavonoids were detected with significant changes. Combined with a KEGG enrichment analysis, we revealed 16 differentially expressed genes (DEGs) in alkaloid-related arginine and proline metabolism, 60 DEGs were identified in the phenolic acid-related phenylpropane biosynthesis, and 30 DEGs were identified in the flavonoid-related biosynthesis pathway. In addition, some highly correlated differential-expression genes with differential metabolites were further identified by correlation analysis. The present research provides a preliminary view of the effects of NOR-like1 transcription factor on alkaloid, phenolic acid, and flavonoid accumulation in tomatoes at different ripening stages based on widely targeted metabolomics and transcriptomics in plants, laying the foundation for extending fruit longevity and shelf life as well as cultivating stress-resistant plants.
A Deep-Learning-Based Guidewire Compliant Control Method for the Endovascular Surgery Robot
Authors: Lyu Chuqiao , Guo Shuxiang , Zhou Wei , Yan Yonggan , Yang Chenguang , Wang Yue , Meng Fanxu
Published: December 2022

Endovascular surgery is a high-risk operation with limited vision and intractable guidewires. At present, endovascular surgery robot (ESR) systems based on force feedback liberates surgeons’ operation skills, but it lacks the ability to combine force perception with vision. In this study, a deep learning-based guidewire-compliant control method (GCCM) is proposed, which guides the robot to avoid surgical risks and improve the efficiency of guidewire operation. First, a deep learning-based model called GCCM-net is built to identify whether the guidewire tip collides with the vascular wall in real time. The experimental results in a vascular phantom show that the best accuracy of GCCM-net is 94.86 ± 0.31%. Second, a real-time operational risk classification method named GCCM-strategy is proposed. When the surgical risks occur, the GCCM-strategy uses the result of GCCM-net as damping and decreases the robot’s running speed through virtual resistance. Compared with force sensors, the robot with GCCM-strategy can alleviate the problem of force position asynchrony caused by the long and soft guidewires in real-time. Experiments run by five guidewire operators show that the GCCM-strategy can reduce the average operating force by 44.0% and shorten the average operating time by 24.6%; therefore the combination of vision and force based on deep learning plays a positive role in improving the operation efficiency in ESR.