bluuebunny/crossref_metadata_2025 huggingface dataset:
Process Mining Dashboard in Operating Rooms: Analysis of Staff Expectations with Analytic Hierarchy Process
Authors: Martinez-Millana Antonio , Lizondo Aroa , Gatta Roberto , Vera Salvador , Salcedo Vicente Traver , Fernandez-Llatas Carlos
Published: January 2019

The widespread adoption of real-time location systems is boosting the development of software applications to track persons and assets in hospitals. Among the vast amount of applications, real-time location systems in operating rooms have the advantage of grounding advanced data analysis techniques to improve surgical processes, such as process mining. However, such applications still find entrance barriers in the clinical context. In this paper, we aim to evaluate the preferred features of a process mining-based dashboard deployed in the operating rooms of a hospital equipped with a real-time location system. The dashboard allows to discover and enhance flows of patients based on the location data of patients undergoing an intervention. Analytic hierarchy process was applied to quantify the prioritization of the dashboard features (filtering data, enhancement, node selection, statistics, etc.), distinguishing the priorities that each of the different roles in the operating room service assigned to each feature. The staff in the operating rooms (n = 10) was classified into three groups: Technical, clinical, and managerial staff according to their responsibilities. Results showed different weights for the features in the process mining dashboard for each group, suggesting that a flexible process mining dashboard is needed to boost its potential in the management of clinical interventions in operating rooms. This paper is an extension of a communication presented in the Process-Oriented Data Science for Health Workshop in the Business Process Management Conference 2018.
Efficacy of Azatyrosine-Phenylbutyric Hydroxamides, a Histone Deacetylase Inhibitor, on Chemotherapy-Induced Gastrointestinal Mucositis
Authors: Liao Po-Lin , Huang Shih-Hsuan , Hung Chien-Hung , Huang Wei-Kuang , Tsai Chi-Hao , Kang Jaw-Jou , Wang Hui-Po , Cheng Yu-Wen
Published: January 2019

Gastrointestinal mucositis is a serious side effect of chemotherapy. Currently, no effective treatment exists for chemotherapy-induced mucositis, prompting the need to develop an anti-mucositis agent for use in clinics. The present study investigated whether azatyrosine-PBHA (AzP), a histone deacetylase inhibitor, has a therapeutic effect on intestinal mucosa. The results indicated that AzP did not affect the proliferation and viability of cancer cells, outcomes that are achieved by suberoylanilide hydroxamic acid (SAHA). However, AzP could decrease production of the inflammatory mediators interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and tumor-necrosis factor-α (TNF-α). In vivo histopathological assessment showed that AzP reduced cisplatin-induced injury to the jejunum villi and triggered weight loss in the C57BL/6 mice. Immunohistochemistry (IHC) results demonstrated that mice treated with AzP also recovered from cisplatin-induced injury to the intestinal mucosa. Mechanistic in vitro study using DAVID/KEGG enrichment analysis of microarray data and confirmation by a Western blot indicated the influence of AzP on the MEK/ERK and AKT-dependent pathway. In conclusion, the study demonstrated that AzP might regulate the MEK/ERK MAPK signaling pathway to attenuate MCP-1, TNF-α, and IL-6 production and provide opportunities for the development of new anti-inflammatory drugs targeting mucositis.
Overview of the Structure–Function Relationships of Mannose-Specific Lectins from Plants, Algae and Fungi
Authors: Barre Annick , Bourne Yves , Van Damme Els J. M. , Rougé Pierre
Published: January 2019

To date, a number of mannose-binding lectins have been isolated and characterized from plants and fungi. These proteins are composed of different structural scaffold structures which harbor a single or multiple carbohydrate-binding sites involved in the specific recognition of mannose-containing glycans. Generally, the mannose-binding site consists of a small, central, carbohydrate-binding pocket responsible for the “broad sugar-binding specificity” toward a single mannose molecule, surrounded by a more extended binding area responsible for the specific recognition of larger mannose-containing N-glycan chains. Accordingly, the mannose-binding specificity of the so-called mannose-binding lectins towards complex mannose-containing N-glycans depends largely on the topography of their mannose-binding site(s). This structure–function relationship introduces a high degree of specificity in the apparently homogeneous group of mannose-binding lectins, with respect to the specific recognition of high-mannose and complex N-glycans. Because of the high specificity towards mannose these lectins are valuable tools for deciphering and characterizing the complex mannose-containing glycans that decorate both normal and transformed cells, e.g., the altered high-mannose N-glycans that often occur at the surface of various cancer cells.
Decreased Serum Brain-Derived Neurotrophic Factor (BDNF) Levels in Patients with Alzheimer’s Disease (AD): A Systematic Review and Meta-Analysis
Authors: Ng Ted Kheng Siang , Ho Cyrus Su Hui , Tam Wilson Wai San , Kua Ee Heok , Ho Roger Chun-Man
Published: January 2019

Findings from previous studies reporting the levels of serum brain-derived neurotrophic factor (BDNF) in patients with Alzheimer’s disease (AD) and individuals with mild cognitive impairment (MCI) have been conflicting. Hence, we performed a meta-analysis to examine the aggregate levels of serum BDNF in patients with AD and individuals with MCI, in comparison with healthy controls. Fifteen studies were included for the comparison between AD and healthy control (HC) (n = 2067). Serum BDNF levels were significantly lower in patients with AD (SMD: −0.282; 95% confidence interval [CI]: −0.535 to −0.028; significant heterogeneity: I2 = 83.962). Meta-regression identified age (p < 0.001) and MMSE scores (p < 0.001) to be the significant moderators that could explain the heterogeneity in findings in these studies. Additionally, there were no significant differences in serum BDNF levels between patients with AD and MCI (eight studies, n = 906) and between MCI and HC (nine studies, n = 5090). In all, patients with AD, but not MCI, have significantly lower serum BDNF levels compared to healthy controls. This meta-analysis confirmed the direction of change in serum BDNF levels in dementia. This finding suggests that a significant change in peripheral BDNF levels can only be detected at the late stage of the dementia spectrum. Molecular mechanisms, implications on interventional trials, and future directions for studies examining BDNF in dementia were discussed.
IL-1β Inflammatory Cytokine-Induced TP63 Isoform ∆NP63α Signaling Cascade Contributes to Cisplatin Resistance in Human Breast Cancer Cells
Authors: Mendoza-Rodríguez Mónica G. , Ayala-Sumuano Jorge T. , García-Morales Lázaro , Zamudio-Meza Horacio , Pérez-Yepez Eloy A. , Meza Isaura
Published: January 2019

The mechanisms behind the induction of malignancy and chemoresistance in breast cancer cells are still not completely understood. Inflammation is associated with the induction of malignancy in different types of cancer and is highlighted as an important factor for chemoresistance. In previous work, we demonstrated that the inflammatory cytokine interleukin 1β (IL-1β)-induced upregulation of genes was associated with chemoresistance in breast cancer cells. Here, we evaluated the participation and the expression profile of TP63 in the induction of resistance to cisplatin. By loss-of-function assays, we identified that IL-1β particularly upregulates the expression of the tumor protein 63 (TP63) isoform ΔNP63α, through the activation of the IL-1β/IL-1RI/β-catenin signaling pathway. Upregulation of ΔNP63α leads to an increase in the expression of the cell survival factors epidermal growth factor receptor (EGFR) and phosphatase 1D (Wip1), and a decrease in the DNA damage sensor, ataxia-telangiectasia mutated (ATM). The participation of these processes in the increase of resistance to cisplatin was confirmed by silencing TP63 expression or by inhibition of the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) activity in the IL-1β/IL-1RI/β-catenin signaling pathway. These data reinforced the importance of an inflammatory environment in the induction of drug resistance in cancer cells and uncovered a molecular mechanism where the IL-1β signaling pathway potentiates the acquisition of cisplatin resistance in breast cancer cells.
Brain-Derived Neurotrophin and TrkB in Head and Neck Squamous Cell Carcinoma
Authors: Dudás József , Riml Anna , Tuertscher Raphaela , Pritz Christian , Steinbichler Teresa Bernadette , Schartinger Volker Hans , Sprung Susanne , Glueckert Rudolf , Schrott-Fischer Anneliese , Johnson Chacko Lejo , Riechelmann Herbert
Published: January 2019

We hypothesized that in head and neck squamous cell carcinoma (HNSCC), the neurotrophin brain-derived neurotrophic factor (BDNF) and its high affinity receptor TrkB regulate tumor cell survival, invasion, and therapy resistance. We used in situ hybridization for BDNF and immunohistochemistry (IHC) for TrkB in 131 HNSCC samples. Brain-derived neurotrophic factor was highly expressed in normal mucosa in HNSCC tissue and in cell lines, whereas only 42.74% of HNSCC tissue was TrkB+. One fourth of HNSCC cases was human papilloma virus (HPV)− positive, but the TrkB IHC frequency was not different in HPV-positive (HPV+) and negative cases. The UPCI-SCC090 cells expressed constitutive levels of TrkB. Transforming-growth-factor-β1 (1 ng/mL TGF-β1) induced TrkB in a subpopulation of SCC-25 cells. A single 10-µg/mL mitomycin C treatment in UPCI-SCC090 cells induced apoptosis and BDNF did not rescue them. The SCC-25 cells were resistant to the MMC treatment, and their growth decreased after TGF-β1 treatment, but was restored by BDNF if it followed TGF-β1. Taken together, BDNF might be ineffective in HPV+ HNSCC patients. In HPV− HNSCC patients, tumor cells did not die after chemotherapeutic challenge and BDNF with TGF-β1 could improve tumor cell survival and contribute to worse patient prognosis.
PPP3CB Inhibits Migration of G401 Cells via Regulating Epithelial-to-Mesenchymal Transition and Promotes G401 Cells Growth
Authors: Chen Lei , He Qingling , Liu Yamin , Wu Yafei , Ni Dongsheng , Liu Jianing , Hu Yanxia , Gu Yuping , Xie Yajun , Zhou Qin , Li Qianyin
Published: January 2019

PPP3CB belongs to the phosphoprotein phosphatases (PPPs) group. Although the majority of the PPP family play important roles in the epithelial-to-mesenchymal transition (EMT) of tumor cells, little is known about the function of PPP3CB in the EMT process. Here, we found PPP3CB had high expression in kidney mesenchymal-like cells compared with kidney epithelial-like cells. Knock-down of PPP3CB downregulated epithelial marker E-cadherin and upregulated mesenchymal marker Vimentin, promoting the transition of cell states from epithelial to mesenchymal and reorganizing the actin cytoskeleton which contributed to cell migration. Conversely, overexpression of PPP3CB reversed EMT and inhibited migration of tumor cells. Besides, in vitro and in vivo experiments indicated that the loss of PPP3CB suppressed the tumor growth. However, the deletion of the phosphatase domain of PPP3CB showed no effect on the expression of E-cadherin, migration, and G401 cell proliferation. Together, we demonstrate that PPP3CB inhibits G401 cell migration through regulating EMT and promotes cell proliferation, which are both associated with the phosphatase activity of PPP3CB.
SLC35A5 Protein—A Golgi Complex Member with Putative Nucleotide Sugar Transport Activity
Authors: Sosicka Paulina , Bazan Bożena , Maszczak-Seneczko Dorota , Shauchuk Yauhen , Olczak Teresa , Olczak Mariusz
Published: January 2019

Solute carrier family 35 member A5 (SLC35A5) is a member of the SLC35A protein subfamily comprising nucleotide sugar transporters. However, the function of SLC35A5 is yet to be experimentally determined. In this study, we inactivated the SLC35A5 gene in the HepG2 cell line to study a potential role of this protein in glycosylation. Introduced modification affected neither N- nor O-glycans. There was also no influence of the gene knock-out on glycolipid synthesis. However, inactivation of the SLC35A5 gene caused a slight increase in the level of chondroitin sulfate proteoglycans. Moreover, inactivation of the SLC35A5 gene resulted in the decrease of the uridine diphosphate (UDP)-glucuronic acid, UDP-N-acetylglucosamine, and UDP-N-acetylgalactosamine Golgi uptake, with no influence on the UDP-galactose transport activity. Further studies demonstrated that SLC35A5 localized exclusively to the Golgi apparatus. Careful insight into the protein sequence revealed that the C-terminus of this protein is extremely acidic and contains distinctive motifs, namely DXEE, DXD, and DXXD. Our studies show that the C-terminus is directed toward the cytosol. We also demonstrated that SLC35A5 formed homomers, as well as heteromers with other members of the SLC35A protein subfamily. In conclusion, the SLC35A5 protein might be a Golgi-resident multiprotein complex member engaged in nucleotide sugar transport.
Acknowledgement to Reviewers of Information in 2018
Authors: Office Information Editorial
Published: January 2019

Rigorous peer-review is the corner-stone of high-quality academic publishing [...]
Acknowledgement to Reviewers of Journal of Cardiovascular Development and Disease in 2018
Authors:   Journal of Cardiovascular Development and Disease Editorial Office
Published: January 2019

Rigorous peer-review is the corner-stone of high-quality academic publishing[...]
A Review on the Corrosion Behaviour of Nanocoatings on Metallic Substrates
Authors: Abdeen Dana H. , El Hachach Mohamad , Koc Muammer , Atieh Muataz A.
Published: January 2019

Growth in nanocoatings technology is moving towards implementing nanocoatings in many sectors of the industry due to their excellent abilities. Nanocoatings offer numerous advantages, including surface hardness, adhesive strength, long-term and/or high-temperature corrosion resistance, the enhancement of tribological properties, etc. In addition, nanocoatings can be applied in thinner and smoother thickness, which allows flexibility in equipment design, improved efficiency, lower fuel economy, lower carbon footprints, and lower maintenance and operating costs. Nanocoatings are utilised efficiently to reduce the effect of a corrosive environment. A nanocoating is a coating that either has constituents in the nanoscale, or is composed of layers that are less than 100 nm. The fine sizes of nanomaterials and the high density of their ground boundaries enable good adhesion and an excellent physical coverage of the coated surface. Yet, such fine properties might form active sites for corrosion attack. This paper reviews the corrosion behaviour of metallic, ceramic, and nanocomposite coatings on the surface of metallic substrates. It summarises the factors affecting the corrosion of these substrates, as well as the conditions where such coatings provided required protection.
Revealing High Oxygen Evolution Catalytic Activity of Fluorine-Doped Carbon in Alkaline Media
Authors: Kim Jeheon , Fukushima Tomohiro , Zhou Ruifeng , Murakoshi Kei
Published: January 2019

Oxygen evolution reactions (OER) are important reactions for energy conversion. Metal-free carbon-based catalysts potentially contribute to the catalytic materials for OER. However, it has been difficult to understand the intrinsic catalytic activity of carbon materials, due to catalyst decomposition over the course of long-term reactions. Here, we report high oxygen evolution reaction catalytic activity of F-doped carbon in alkaline media. Intrinsic OER activity was evaluated from a combination of measurements using a rotating disk electrode and O2 sensor. The F-doped carbon catalyst is a highly active catalyst, comparable to state-of-the-art precious-metal-based catalysts such as RuO2.
Heat Treatment of AZ91 Magnesium Alloy Coated with an Al2O3 Thin Film with Fluidized Bed Technology
Authors: Baiocco Gabriele , Rubino Gianluca , Ucciardello Nadia
Published: January 2019

Fluidized bed technology is a methodology widely known in the manufacturing environment for surface treatment of metals. Within the field of surface coating, it has already been exploited for the coating of a magnesium alloy creating a compact layer of Al2O3. The result was an improvement in mechanical and tribological properties, along with improved corrosion resistance. In this context, the work proposed is addressed towards the evaluation of the effects of thermal post-treatment on the alumina coating produced by means of the fluidized-bed technology. To analyse the effects of heat treatments the morphology, composition and hardness of the samples were investigated along with adhesion and wear resistance of the alumina film. The results obtained show how the temperature affects the surface morphology and promotes the diffusion of magnesium towards the alumina superficial layer. The mechanisms triggered by heat treatments increase the adhesion of the surface film obtained in the deposition process, improving its mechanical and tribological properties.
The Rheology of PEOT/PBT Block Copolymers in the Melt State and in the Thermally-Induced Sol/Gel Transition Implications on the 3D-Printing Bio-Scaffold Process
Authors: Vanzanella Veronica , Scatto Marco , Zant Erwin , Sisani Michele , Bastianini Maria , Grizzuti Nino
Published: January 2019

Poly(ethylene oxide terephthalate)/poly(butylene terephthalate) (PEOT/PBT) segmented block copolymers are widely used for the manufacturing of 3D-printed bio-scaffolds, due to a combination of several properties, such as cell viability, bio-compatibility, and bio-degradability. Furthermore, they are characterized by a relatively low viscosity at high temperatures, which is desired during the injection stages of the printing process. At the same time, the microphase separated morphology generated by the demixing of hard and soft segments at intermediate temperatures allows for a quick transition from a liquid-like to a solid-like behavior, thus favoring the shaping and the dimensional stability of the scaffold. In this work, for the first time, the rheology of a commercial PEOT/PBT material is studied over a wide range of temperatures encompassing both the melt state and the phase transition regime. Non-isothermal viscoelastic measurements under oscillatory shear flow allow for a quantitative determination of the material processability in the melt state. Additionally, isothermal experiments below the order–disorder temperature are used to determine the temperature dependence of the phase transition kinetics. The importance of the rheological characterization when designing the 3D-printing scaffold process is also discussed.
Embrittlement Due to Excess Heat Input into Friction Stir Processed 7075 Alloy
Authors: Ku Ming-Hsiang , Hung Fei-Yi , Lui Truan-Sheng
Published: January 2019

The grain size of high strength 7075 hot-rolled aluminum plates was refined by a friction stir process (FSP) to improve their mechanical properties. The results of the tensile ductility tests, which were conducted at various tool rotational speeds, in the friction stir zone indicate significant tensile ductility loss, which even resulted in a ductile-to-brittle transition (DBT). DBT depends on the tool rotational speed. Our 1450 rpm specimens showed large data fluctuation in the tensile ductility and the location of the fracture controlled the formation of friction stir induced bands (FSIB). The crack initiation site located at FSIB was due to the tool rotational speed (1670 rpm). A higher heat-input causes the formation of FSIB, which is accompanied with micro-voids. This contributes significantly to tensile cracking within the stir zone after the application of the aging treatment. This investigation aimed to determine the dominant factor causing tensile ductility loss at the stir zone, which is the major restriction preventing further applications.
Structural and Thermoelectric Properties of Cu Substituted Type I Clathrates Ba8CuxSi~32−xGa~14
Authors: Dong Yue , Ding Xueyong , Yan Xinlin , Zhang Long , Ju Tianhua , Liu Chenghong , Rogl Peter , Paschen Silke
Published: January 2019

With an attempt to improve the thermoelectric properties of type I clathrates in the Ba-Ga-Si system, we introduce Cu into the framework of the crystal structure. Single crystals are prepared in Ga-flux and characterized by X-ray diffraction techniques and transport measurements for the structural and thermoelectric properties. Our composition analyses show that only a small amount of Cu is determined in the clathrates. The single crystal X-ray diffraction data refinements confirm that Ga atoms prefer the 6c and 24k sites and avoid the 16i sites in the crystal structure. The small amount of Cu affects the crystal structure by compressing the tetrakaidecahedral cage along the direction perpendicular to the six-atom-ring plane. This could be the reason for the high charge carrier concentration, and low electrical resistivity and Seebeck coefficient. We analyze the principal mechanism for our observation and conclude that the Cu substitution can adjust some subtle details of the structure, maintaining the Zintl rule in the type I clathrates.
Tribonacci and Tribonacci-Lucas Sedenions
Authors: Soykan Yüksel
Published: January 2019

The sedenions form a 16-dimensional Cayley-Dickson algebra. In this paper, we introduce the Tribonacci and Tribonacci-Lucas sedenions. Furthermore, we present some properties of these sedenions and derive relationships between them.
From Aggregates to Porous Three-Dimensional Scaffolds through a Mechanochemical Approach to Design Photosensitive Chitosan Derivatives
Authors: Bardakova Kseniia N. , Akopova Tatiana A. , Kurkov Alexander V. , Goncharuk Galina P. , Butnaru Denis V. , Burdukovskii Vitaliy F. , Antoshin Artem A. , Farion Ivan A. , Zharikova Tatiana M. , Shekhter Anatoliy B. , Yusupov Vladimir I. , Timashev Peter S. , Rochev Yury A.
Published: January 2019

The crustacean processing industry produces large quantities of waste by-products (up to 70%). Such wastes could be used as raw materials for producing chitosan, a polysaccharide with a unique set of biochemical properties. However, the preparation methods and the long-term stability of chitosan-based products limit their application in biomedicine. In this study, different scale structures, such as aggregates, photo-crosslinked films, and 3D scaffolds based on mechanochemically-modified chitosan derivatives, were successfully formed. Dynamic light scattering revealed that aggregation of chitosan derivatives becomes more pronounced with an increase in the number of hydrophobic substituents. Although the results of the mechanical testing revealed that the plasticity of photo-crosslinked films was 5–8% higher than that for the initial chitosan films, their tensile strength remained unchanged. Different types of polymer scaffolds, such as flexible and porous ones, were developed by laser stereolithography. In vivo studies of the formed structures showed no dystrophic and necrobiotic changes, which proves their biocompatibility. Moreover, the wavelet analysis was used to show that the areas of chitosan film degradation were periodic. Comparing the results of the wavelet analysis and X-ray diffraction data, we have concluded that degradation occurs within less ordered amorphous regions in the polymer bulk.
CYC27 Synthetic Derivative of Bromophenol from Red Alga Rhodomela confervoides: Anti-Diabetic Effects of Sensitizing Insulin Signaling Pathways and Modulating RNA Splicing-Associated RBPs
Authors: Luo Jiao , Jiang Bo , Li Chao , Jia Xiaoling , Shi Dayong
Published: January 2019

RNA-binding proteins (RBPs) lie at the center of posttranscriptional regulation and the dysregulation of RBPs contributes to diabetes. Therefore, the modulation of RBPs is anticipated to become a potential therapeutic approach to diabetes. CYC27 is a synthetic derivative of marine bromophenol BDB, which is isolated from red alga Rhodomela confervoides. In this study, we found that CYC27 significantly lowered the blood glucose levels of diabetic BKS db mice. Moreover, CYC27 effectively ameliorated dyslipidemia in BKS db mice by reducing their total serum cholesterol (TC) and triglyceride (TG) levels. Furthermore, CYC27 was an insulin-sensitizing agent with increased insulin-stimulated phosphorylation of insulin receptors and relevant downstream factors. Finally, to systemically study the mechanisms of CYC27, label-free quantitative phosphoproteomic analysis was performed to investigate global changes in phosphorylation. Enriched GO annotation showed that most regulated phosphoproteins were related to RNA splicing and RNA processing. Enriched KEGG analysis showed that a spliceosome-associated pathway was the predominant pathway after CYC27 treatment. Protein-protein interaction (PPI) analysis showed that CYC27 modulated the process of mRNA splicing via phosphorylation of the relevant RBPs, including upregulated Cstf3 and Srrt. Our results suggested that CYC27 treatment exerted promising anti-diabetic effects by sensitizing the insulin signaling pathways and modulating RNA splicing-associated RBPs.
A Case of Isolated Cecal Necrosis Preoperatively Diagnosed with Perforation of Cecum
Authors: Kohga Atsushi , Yajima Kiyoshige , Okumura Takuya , Yamashita Kimihiro , Isogaki Jun , Suzuki Kenji , Komiyama Akira , Kawabe Akihiro
Published: January 2019

Isolated cecal necrosis (ICN) is a rare condition which is developed under decreased mesenteric perfusion. Only a few dozen cases of ICN have been reported previously. The patient was a 59-year-old male with a previous history of atrial fibrillation. He presented to our emergency room with the chief complaint of lower abdominal pain. Computed tomography imaging revealed a dilated cecum and presence of free air. With a preoperative diagnosis of perforation of the cecum; an urgent surgery was conducted. Intraoperative findings revealed an ischemic change of the cecum and a laparoscopic-assisted ileocecal resection was performed. The pathological findings showed transmural ischemic change on the anti-mesenteric side of the cecum, and the diagnosis of ICN was achieved. Preoperative diagnosis of ICN is difficult because of its non-specific radiological features. In patients with right lower abdominal pain, ICN should be considered as a differential diagnosis especially if the patient has a comorbidity causing hypotension attack.
Direct Infusion Based Metabolomics Identifies Metabolic Disease in Patients’ Dried Blood Spots and Plasma
Authors: Haijes Hanneke A. , Willemsen Marcel , Van der Ham Maria , Gerrits Johan , Pras-Raves Mia L. , Prinsen Hubertus C. M. T. , Van Hasselt Peter M. , De Sain-van der Velden Monique G. M. , Verhoeven-Duif Nanda M. , Jans Judith J. M.
Published: January 2019

In metabolic diagnostics, there is an emerging need for a comprehensive test to acquire a complete view of metabolite status. Here, we describe a non-quantitative direct-infusion high-resolution mass spectrometry (DI-HRMS) based metabolomics method and evaluate the method for both dried blood spots (DBS) and plasma. 110 DBS of 42 patients harboring 23 different inborn errors of metabolism (IEM) and 86 plasma samples of 38 patients harboring 21 different IEM were analyzed using DI-HRMS. A peak calling pipeline developed in R programming language provided Z-scores for ~1875 mass peaks corresponding to ~3835 metabolite annotations (including isomers) per sample. Based on metabolite Z-scores, patients were assigned a ‘most probable diagnosis’ by an investigator blinded for the known diagnoses of the patients. Based on DBS sample analysis, 37/42 of the patients, corresponding to 22/23 IEM, could be correctly assigned a ‘most probable diagnosis’. Plasma sample analysis, resulted in a correct ‘most probable diagnosis’ in 32/38 of the patients, corresponding to 19/21 IEM. The added clinical value of the method was illustrated by a case wherein DI-HRMS metabolomics aided interpretation of a variant of unknown significance (VUS) identified by whole-exome sequencing. In summary, non-quantitative DI-HRMS metabolomics in DBS and plasma is a very consistent, high-throughput and nonselective method for investigating the metabolome in genetic disease.
Rapid Cerebral Metabolic Shift during Neonatal Sepsis Is Attenuated by Enteral Colostrum Supplementation in Preterm Pigs
Authors: Alinaghi Masoumeh , Jiang Ping-Ping , Brunse Anders , Sangild Per Torp , Bertram Hanne Christine
Published: January 2019

Sepsis, the clinical manifestation of serious infection, may disturb normal brain development, especially in preterm infants with an immature brain. We hypothesized that neonatal sepsis induces systemic metabolic alterations that rapidly affect metabolic signatures in immature brain and cerebrospinal fluid (CSF). Cesarean-delivered preterm pigs systemically received 109 CFU/kg Staphylococcus epidermidis (SE) and were provided total parenteral nutrition (n = 9) or enteral supplementation with bovine colostrum (n = 10) and compared with uninfected pigs receiving parenteral nutrition (n = 7). Plasma, CSF, and brain tissue samples were collected after 24 h and analyzed by 1H NMR-based metabolomics. Both plasma and CSF metabolomes revealed SE-induced changes in metabolite levels that reflected a modified energy metabolism. Hence, increased plasma lactate, alanine, and succinate levels, as well as CSF lactate levels, were observed during SE infection (all p < 0.05, ANOVA analysis). Myo-inositol, a glucose derivative known for beneficial effects on lung maturation in preterm infants, was also increased in plasma and CSF following SE infection. Enteral colostrum supplementation attenuated the lactate accumulation in blood and CSF. Bloodstream infection in preterm newborns was found to induce a rapid metabolic shift in both plasma and CSF, which was modulated by colostrum feeding.
Recent Developments of Acoustic Energy Harvesting: A Review
Authors: Yuan Ming , Cao Ziping , Luo Jun , Chou Xiujian
Published: January 2019

Acoustic energy is a type of environmental energy source that can be scavenged and converted into electrical energy for small-scale power applications. In general, incident sound power density is low and structural design for acoustic energy harvesting (AEH) is crucial. This review article summarizes the mechanisms of AEH, which include the Helmholtz resonator approach, the quarter-wavelength resonator approach, and the acoustic metamaterial approach. The details of recently proposed AEH devices and mechanisms are carefully reviewed and compared. Because acoustic metamaterials have the advantages of compactness, effectiveness, and flexibility, it is suggested that the emerging metamaterial-based AEH technique is highly suitable for further development. It is demonstrated that the AEH technique will become an essential part of the environmental energy-harvesting research field. As a multidisciplinary research topic, the major challenge is to integrate AEH devices into engineering structures and make composite structures smarter to achieve large-scale AEH.
Identification of the Chemical Constituents of an Anti-Arthritic Chinese Medicine Wen Luo Yin by Liquid Chromatography Coupled with Mass Spectrometry
Authors: Guan Huanyu , Luo Xiaomei , Chang Xiaoyan , Su Meifeng , Li Zhuangzhuang , Li Pengfei , Wang Xiaoming , Shi Yue
Published: January 2019

Wen Luo Yin (WLY), a well-known traditional Chinese medicine formulation, has been used as a complementary therapy for the treatment of rheumatoid arthritis in clinical settings. However, the chemical constituents of WLY remain unclear. In this study, a high-performance liquid chromatography coupled with tandem mass spectrometry method was established to separate and comprehensively identify the chemical constituents of WLY. The analytes were eluted with a mobile phase of acetonitrile and 0.1% aqueous acetic acid. Mass detection was performed in both positive and negative ion mode. The MS/MS fragmentation pathways were proposed for the identification of the components. A total of 42 compounds including sesquiterpenes, alkaloids, biflavonoids, polyacetylenes, phenylpropanoids and acetylenic phenols were identified unambiguously or tentatively according to their retention times and mass behavior with those of authentic standards or literature data. The identification and structural elucidation of chemical constituents may provide important information for quality control and pharmacological research of WLY.
Pharmacokinetic Properties of Arsenic Species after Intravenous and Intragastrical Administration of Arsenic Trioxide Solution in Cynomolgus Macaques Using HPLC-ICP-MS
Authors: Shi Qiaoli , Ju Mingyan , Zhu Xiaoxia , Gan Hui , Gu Ruolan , Wu Zhuona , Meng Zhiyun , Dou Guifang
Published: January 2019

A rapid and sensitive method was established for arsenic (As) speciation based on high performance liquid chromatography coupled to inductively coupled plasma mass spectrometry (HPLC-ICP-MS). This method was validated for the quantification of four arsenic species, including arsenite (AsIII), arsenate (AsV), monomethylarsonic acid (MMAV) and dimethylarsinic acid (DMAV) in cynomolgus macaque plasma. Separation was achieved in just 3.7 min with an alkyl reverse phase column and highly aqueous mobile phase containing 20 mM citric acid and 5 mM sodium hexanesulfonate (pH = 4.3). The calibration curves were linear over the range of 5–500 ng·mL−1 (measured as As), with r > 0.99. The above method was validated for selectivity, precision, accuracy, matrix effect, recovery, carryover effect and stability, and applied in a comparative pharmacokinetic study of arsenic species in cynomolgus macaque samples following intravenous and intragastrical administration of arsenic trioxide solution (0.80 mg·kg−1; 0.61 mg·kg−1 of arsenic); in addition, the absolute oral bioavailability of the active ingredient AsIII of arsenic trioxide in cynomolgus macaque samples was derived as 60.9 ± 16.1%.
Resonance Raman Spectro-Electrochemistry to Illuminate Photo-Induced Molecular Reaction Pathways
Authors: Zedler Linda , Krieck Sven , Kupfer Stephan , Dietzek Benjamin
Published: January 2019

Electron transfer reactions play a key role for artificial solar energy conversion, however, the underlying reaction mechanisms and the interplay with the molecular structure are still poorly understood due to the complexity of the reaction pathways and ultrafast timescales. In order to investigate such light-induced reaction pathways, a new spectroscopic tool has been applied, which combines UV-vis and resonance Raman spectroscopy at multiple excitation wavelengths with electrochemistry in a thin-layer electrochemical cell to study [RuII(tbtpy)2]2+ (tbtpy = tri-tert-butyl-2,2′:6′,2′′-terpyridine) as a model compound for the photo-activated electron donor in structurally related molecular and supramolecular assemblies. The new spectroscopic method substantiates previous suggestions regarding the reduction mechanism of this complex by localizing photo-electrons and identifying structural changes of metastable intermediates along the reaction cascade. This has been realized by monitoring selective enhancement of Raman-active vibrations associated with structural changes upon electronic absorption when tuning the excitation wavelength into new UV-vis absorption bands of intermediate structures. Additional interpretation of shifts in Raman band positions upon reduction with the help of quantum chemical calculations provides a consistent picture of the sequential reduction of the individual terpyridine ligands, i.e., the first reduction results in the monocation [(tbtpy)Ru(tbtpy•)]+, while the second reduction generates [(tbtpy•)Ru(tbtpy•)]0 of triplet multiplicity. Therefore, the combination of this versatile spectro-electrochemical tool allows us to deepen the fundamental understanding of light-induced charge transfer processes in more relevant and complex systems.
Metabolomics Profiling Reveals Rehmanniae Radix Preparata Extract Protects against Glucocorticoid-Induced Osteoporosis Mainly via Intervening Steroid Hormone Biosynthesis
Authors: Xia Tianshuang , Dong Xin , Jiang Yiping , Lin Liuyue , Dong Zhimin , Shen Yi , Xin Hailiang , Zhang Qiaoyan , Qin Luping
Published: January 2019

Rehmanniae Radix Preparata (RR), the dry rhizome of Rehmannia glutinosa Libosch., is a traditional herbal medicine for improving the liver and kidney function. Ample clinical and pharmacological experiments show that RR can prevent post-menopausal osteoporosis and senile osteoporosis. In the present study, in vivo and in vitro experiments, as well as a UHPLC-Q/TOF-MS-based metabolomics study, were used to explore the preventing effect of RR on glucocorticoid-induced osteoporosis (GIOP) and its underlying mechanisms. As a result, RR significantly enhanced bone mineral density (BMD), improved the micro-architecture of trabecular bone, and intervened in biochemical markers of bone metabolism in dexamethasone (DEX)-treated rats. For the in vitro experiment, RR increased the cell proliferation and alkaline phosphatase (ALP) activity, enhanced the extracellular matrix mineralization level, and improved the expression of runt-related transcription factor 2 (RUNX2) and osteopontin (OPN) in DEX-injured osteoblasts. For the metabolomics study, a total of 27 differential metabolites were detected in the DEX group vs. the control group, of which 10 were significantly reversed after RR treatment. These metabolites were majorly involved in steroid hormone biosynthesis, sex steroids regulation, and amino acid metabolism. By metabolic pathway and Western blotting analysis, it was further ascertained that RR protected against DEX-induced bone loss, mainly via interfering steroid hormone biosynthesis, as evidenced by the up-regulation of cytochrome P450 17A1 (CYP17A1) and aromatase (CYP19A1), and the down-regulation of 11β-hydroxysteroid dehydrogenase (HSD11B1). Collectively, these results indicated that RR had a notable preventing effect on GIOP, and the action mechanism might be related to steroid hormone biosynthesis.
Anti-Allergic and Anti-Inflammatory Effects of Kuwanon G and Morusin on MC/9 Mast Cells and HaCaT Keratinocytes
Authors: Jin Seong Eun , Ha Hyekyung , Shin Hyeun-Kyoo , Seo Chang-Seob
Published: January 2019

Atopic dermatitis (AD) is a prevalent chronic inflammatory skin disease. The use of immunomodulatory corticosteroids in AD treatment causes adverse side effects. Therefore, novel natural anti-inflammatory therapeutics are needed. The aim of the present study was to investigate the anti-allergic and anti-inflammatory activities of kuwanon G and morusin. To investigate the effect of kuwanon G and morusin on skin inflammation, enzyme-linked immunosorbent assays (ELISA) to quantitate secreted (RANTES/CCL5), thymus- and activation-regulated chemokine (TARC/CCL17), and macrophage-derived chemokine (MDC/CCL22) were performed, followed by Western blotting to measure the phosphorylation of signal transducer and activator of transcription 1 (STAT1) and nuclear transcription factor-κB (NF-κB) p65 in tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ)-stimulated HaCaT keratinocytes. In order to evaluate the anti-allergic effects, ELISA to quantify histamine and leukotriene C4 (LTC4) production and Western blotting to measure 5-lipoxygenase (5-LO) activation were performed using PMA and A23187-stimulated MC/9 mast cells. Kuwanon G reduced the release of RANTES/CCL5, TARC/CCL17, and MDC/CCL22 via down-regulation of STAT1 and NF-κB p65 signaling in TNF-α and IFN-γ-stimulated HaCaT keratinocytes. Kuwanon G also inhibited histamine production and 5-LO activation in PMA and A23187-stimulated MC/9 mast cells. Morusin inhibited RANTES/CCL5 and TARC/CCL17 secretion via the suppression of STAT1 and NF-κB p65 phosphorylation in TNF-α and IFN-γ-stimulated HaCaT keratinocytes, and the release of histamine and LTC4 by suppressing 5-LO activation in PMA and A23187-stimulated MC/9 mast cells. Kuwanon G and morusin are potential anti-inflammatory mediators for the treatment of allergic and inflammatory skin diseases such as AD.
Ranolazine-Functionalized Copper Nanoparticles as a Colorimetric Sensor for Trace Level Detection of As3+
Authors: Laghari Gul Naz , Nafady Ayman , Al-Saeedi Sameerah I. , Sirajuddin  , Sherazi Syed Tufail H. , Nisar Jan , Shah Muhammad Raza , Abro Mohammad I. , Arain Munazza , Bhargava Suresh K.
Published: January 2019

This study involves environmentally friendly synthesis of copper nanoparticles in aqueous medium without inert gas protection, using ranolazine as a capping material. UV-Visible (UV-Vis) spectrometry showed that ranolazine-derived copper nanoparticles (Rano-Cu NPs) demonstrate a localized surface plasmon resonance (LSPR) band at 573 nm with brick-red color under optimized parameters, including pH, reaction time, and concentrations of copper salt, hydrazine hydrate, and ranolazine. The coating of ranolazine on the surface of Cu NPs was studied via Fourier transform infrared (FTIR) spectroscopy. Scanning electron microscopy (SEM) revealed that Rano-Cu NPs consist of spherical particles. X-ray diffraction (XRD) verified that Rano-Cu NPs are crystalline in nature. Atomic force microscopy (AFM) showed that the average size of Rano-Cu NPs was 40 ± 2 nm in the range of 22–95 nm. Rano-Cu NPs proved to be highly sensitive as a selective colorimetric sensor for As3+ via color change from brick red to dark green, in the linear range of 3.0 × 10−7 to 8.3 × 10−6 M, with an R² value of 0.9979. The developed sensor is simple, cost effective, highly sensitive, and extremely selective for As3+ detection, showing a low detection limit (LDL) of 1.6 × 10−8 M. The developed sensor was effectively tested for detection of As3+ in some water samples.
Laser-Induced Graphene on Additive Manufacturing Parts
Authors: Jiao Lishi , Chua Zhong Yang , Moon Seung Ki , Song Jie , Bi Guijun , Zheng Hongyu , Lee Byunghoon , Koo Jamyeong
Published: January 2019

Additive manufacturing (AM) has become more prominent in leading industries. Recently, there have been intense efforts to achieve a fully functional 3D structural electronic device by integrating conductive structures into AM parts. Here, we introduce a simple approach to creating a conductive layer on a polymer AM part by CO2 laser processing. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), and Raman spectroscopy were employed to analyze laser-induced modifications in surface morphology and surface chemistry. The results suggest that conductive porous graphene was obtained from the AM-produced carbon precursor after the CO2 laser scanning. At a laser power of 4.5 W, the lowest sheet resistance of 15.9 Ω/sq was obtained, indicating the excellent electrical conductivity of the laser-induced graphene (LIG). The conductive graphene on the AM parts could serve as an electrical interconnection and shows a potential for the manufacturing of electronics components. An interdigital electrode capacitor was written on the AM parts to demonstrate the capability of LIG. Cyclic voltammetry, galvanostatic charge-discharge, and cyclability testing demonstrated good electrochemical performance of the LIG capacitor. These findings may create opportunities for the integration of laser direct writing electronic and additive manufacturing.
Acknowledgement to Reviewers of Non-Coding RNA in 2018
Authors:   Non-Coding RNA Editorial Office
Published: January 2019

Rigorous peer-review is the corner-stone of high-quality academic publishing [...]
Quantifying Sweet Taste Liker Phenotypes: Time for Some Consistency in the Classification Criteria
Authors: Iatridi Vasiliki , Hayes John E. , Yeomans Martin R.
Published: January 2019

Taste hedonics is a well-documented driver of food consumption. The role of sweetness in directing ingestive behavior is largely rooted in biology. One can then intuit that individual differences in sweet-liking may constitute an indicator of variations in the susceptibility to diet-related health outcomes. Despite half a century of research on sweet-liking, the best method to identify the distinct responses to sweet taste is still debated. To help resolve this issue, liking and intensity ratings for eight sucrose solutions ranging from 0 to 1 M were collected from 148 young adults (29% men). Hierarchical cluster analysis (HCA) revealed three response patterns: a sweet-liker (SL) phenotype characterized by a rise in liking as concentration increased, an inverted U-shaped phenotype with maximum liking at 0.25 M, and a sweet-disliker (SD) phenotype characterized by a decline in liking as a function of concentration. Based on sensitivity and specificity analyses, present data suggest the clearest discrimination between phenotypes is seen with 1.0 M sucrose, where a liking rating between −15 and +15 on a −50/+50 scale reliably distinguished individuals with an inverted U-shaped response from the SLs and the SDs. If the efficacy of this approach is confirmed in other populations, the discrimination criteria identified here can serve as the basis for a standard method for classifying sweet taste liker phenotypes in adults.
Quantification of Lutein + Zeaxanthin Presence in Human Placenta and Correlations with Blood Levels and Maternal Dietary Intake
Authors: Thoene Melissa , Anderson-Berry Ann , Van Ormer Matthew , Furtado Jeremy , Soliman Ghada A. , Goldner Whitney , Hanson Corrine
Published: January 2019

Lutein + zeaxanthin (L + Z) are carotenoids recognized in eye health, but less is known about their status during pregnancy. While quantified in maternal and umbilical cord blood, they have never been analyzed in placenta. The purpose of this study is to quantify combined L + Z concentrations in human placenta and correlate with levels in maternal dietary intake, maternal serum, and umbilical cord blood. The proportions of combined L + Z were compared within diet, placenta, maternal serum, and umbilical cord blood among additional carotenoids (lycopene, β-cryptoxanthin, α-carotene, and β-carotene). This Institutional Review Boardapproved cross-sectional study enrolled 82 mother-infant pairs. Placenta, maternal serum, and umbilical cord blood samples were analyzed for carotenoids concentrations. Mothers completed a food frequency questionnaire and demographic/birth outcome data were collected. L + Z were present in placenta, median 0.105 micrograms/gram (mcg/g) and were significantly correlated with maternal serum (r = 0.57; p < 0.001), umbilical cord blood levels (r = 0.49; p = 0.001), but not dietary intake (p = 0.110). L + Z were the most prevalent in placenta (49.1%) umbilical cord blood (37.0%), but not maternal serum (18.6%) or dietary intake (19.4%). Rate of transfer was 16.0%, the highest of all carotenoids. Conclusively, L + Z were identified as the two most prevalent in placenta. Results highlight unique roles L + Z may play during pregnancy.