bluuebunny/crossref_metadata_2025 huggingface dataset:
Inferring the Disease-Associated miRNAs Based on Network Representation Learning and Convolutional Neural Networks
Authors: Xuan Ping , Sun Hao , Wang Xiao , Zhang Tiangang , Pan Shuxiang
Published: July 2019

Identification of disease-associated miRNAs (disease miRNAs) are critical for understanding etiology and pathogenesis. Most previous methods focus on integrating similarities and associating information contained in heterogeneous miRNA-disease networks. However, these methods establish only shallow prediction models that fail to capture complex relationships among miRNA similarities, disease similarities, and miRNA-disease associations. We propose a prediction method on the basis of network representation learning and convolutional neural networks to predict disease miRNAs, called CNNMDA. CNNMDA deeply integrates the similarity information of miRNAs and diseases, miRNA-disease associations, and representations of miRNAs and diseases in low-dimensional feature space. The new framework based on deep learning was built to learn the original and global representation of a miRNA-disease pair. First, diverse biological premises about miRNAs and diseases were combined to construct the embedding layer in the left part of the framework, from a biological perspective. Second, the various connection edges in the miRNA-disease network, such as similarity and association connections, were dependent on each other. Therefore, it was necessary to learn the low-dimensional representations of the miRNA and disease nodes based on the entire network. The right part of the framework learnt the low-dimensional representation of each miRNA and disease node based on non-negative matrix factorization, and these representations were used to establish the corresponding embedding layer. Finally, the left and right embedding layers went through convolutional modules to deeply learn the complex and non-linear relationships among the similarities and associations between miRNAs and diseases. Experimental results based on cross validation indicated that CNNMDA yields superior performance compared to several state-of-the-art methods. Furthermore, case studies on lung, breast, and pancreatic neoplasms demonstrated the powerful ability of CNNMDA to discover potential disease miRNAs.
Molecular Characterization of ZosmaNRT2, the Putative Sodium Dependent High-Affinity Nitrate Transporter of Zostera marina L.
Authors: Rubio Lourdes , Díaz-García Jordi , Amorim-Silva Vítor , Macho Alberto P. , Botella Miguel A. , Fernández José A.
Published: July 2019

One of the most important adaptations of seagrasses during sea colonization was the capacity to grow at the low micromolar nitrate concentrations present in the sea. In contrast to terrestrial plants that use H+ symporters for high-affinity NO3− uptake, seagrasses such as Zostera marina L. use a Na+-dependent high-affinity nitrate transporter. Interestingly, in the Z. marina genome, only one gene (Zosma70g00300.1; NRT2.1) is annotated to this function. Analysis of this sequence predicts the presence of 12 transmembrane domains, including the MFS domains of the NNP transporter family and the “nitrate signature” that appears in all members of the NNP family. Phylogenetic analysis shows that this sequence is more related to NRT2.5 than to NRT2.1, sharing a common ancestor with both monocot and dicot plants. Heterologous expression of ZosmaNRT2-GFP together with the high-affinity nitrate transporter accessory protein ZosmaNAR2 (Zosma63g00220.1) in Nicotiana benthamiana leaves displayed four-fold higher fluorescence intensity than single expression of ZosmaNRT2-GFP suggesting the stabilization of NRT2 by NAR2. ZosmaNRT2-GFP signal was present on the Hechtian-strands in the plasmolyzed cells, pointing that ZosmaNRT2 is localized on the plasma membrane and that would be stabilized by ZosmaNAR2. Taken together, these results suggest that Zosma70g00300.1 would encode a high-affinity nitrate transporter located at the plasma membrane, equivalent to NRT2.5 transporters. These molecular data, together with our previous electrophysiological results support that ZosmaNRT2 would have evolved to use Na+ as a driving ion, which might be an essential adaptation of seagrasses to colonize marine environments.
Tumor-Derived Exosomes Mediate the Instability of Cadherins and Promote Tumor Progression
Authors: Wang Bowen , Tan Zengqi , Guan Feng
Published: July 2019

Cadherins, including E-cadherin, N-cadherin, VE-cadherin, etc., are important adhesion molecules mediating intercellular junctions. The abnormal expression of cadherins is often associated with tumor development and progression. Epithelial–mesenchymal transition (EMT) is the most important step in the metastasis cascade and is accompanied by altered expression of cadherins. Recent studies reveal that as a cargo for intercellular communication, exosomes—one type of extracellular vesicles that can be secreted by tumor cells—are involved in a variety of physiological and pathological processes, especially in tumor metastasis. Tumor-derived exosomes play a crucial role in mediating the cadherin instability in recipient cells by transferring bioactive molecules (oncogenic microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), EMT-related proteins, and others), modulating their local and distant microenvironment, and facilitating cancer metastasis. In turn, aberrant expression of cadherins in carcinoma cells can also affect the biogenesis and release of exosomes. Therefore, we summarize the current research on the crosstalk between tumor-derived exosomes and aberrant cadherin signals to reveal the unique role of exosomes in cancer progression.
Integrated Systems Pharmacology, Urinary Metabonomics, and Quantitative Real-Time PCR Analysis to Uncover Targets and Metabolic Pathways of the You-Gui Pill in Treating Kidney-Yang Deficiency Syndrome
Authors: Chen Ruiqun , Wang Jia , Zhan Runhua , Zhang Lei , Wang Xiufeng
Published: July 2019

Kidney-yang deficiency syndrome (KYDS) is a metabolic disease caused by a neuro-endocrine disorder. The You-gui pill (YGP) is a classic traditional Chinese medicine (TCM) formula for the treatment of KYDS and has been widely used to warm and recuperate KYDS clinically for hundreds of years in China. However, it is unknown whetherthe corresponding targets and metabolic pathways can also be found via using metabonomics based on one platform (e.g., 1H NMR) to study different biological samples of KYDS. At the same time, relevant reports on further molecular verification (e.g., RT-qPCR analysis) of these targets associated with biomarkers and metabolic pathways have not yet, to our knowledge, been seen in KYDS’s research. In the present study, a comprehensive strategy integrating systems pharmacology and 1H NMR-based urinary metabonomics analysis was proposed to identify the target proteins and metabolic pathways that YGP acts on KYDS. Thereafter, further validation of target proteins in kidney tissue was performed through quantitative real-time PCR analysis (RT-qPCR). Furthermore, biochemical parameters and histopathological analysis were studied. As a result, seven target proteins (L-serine dehydratase; phosphoenolpyruvate carboxykinase; spermidine synthase; tyrosyl-tRNA synthetase, glutamine synthetase; 3-hydroxyacyl-CoA dehydrogenase; glycine amidinotransferase) in YGP were discovered to play a therapeutic role in KYDS via affecting eight metabolic pathways (glycine, serine and threonine metabolism; butanoate metabolism; TCA cycle, etc.). Importantly, three target proteins (i.e., 3-hydroxyacyl-CoA dehydrogenase; glutamine synthetase; and glycine amidinotransferase) and two metabolic pathways (butanoate metabolism and dicarboxylate metabolism) related to KYDS, to our knowledge, had been newly discovered in our study. The mechanism of action mainly involved energy metabolism, oxidative stress, ammonia metabolism, amino acid metabolism, and fatty acid metabolism. In short, our study demonstrated that targets and metabolic pathways for the treatment of KYDS by YGP can be effectively found via combining with systems pharmacology and urinary metabonomics. In addition to this, common and specific targets and metabolic pathways of KYDS treated by YGP can be found effectively by integration with the analysis of different biological samples (e.g., serum, urine, feces, and tissue). It is; therefore, important that this laid the foundation for deeper mechanism research and drug-targeted therapy of KYDS in future.
Analysis of Chemically Labile Glycation Adducts in Seed Proteins: Case Study of Methylglyoxal-Derived Hydroimidazolone 1 (MG-H1)
Authors: Antonova Kristina , Vikhnina Maria , Soboleva Alena , Mehmood Tahir , Heymich Marie-Louise , Leonova Tatiana , Bankin Mikhail , Lukasheva Elena , Gensberger-Reigl Sabrina , Medvedev Sergei , Smolikova Galina , Pischetsrieder Monika , Frolov Andrej
Published: July 2019

Seeds represent the major source of food protein, impacting on both human nutrition and animal feeding. Therefore, seed quality needs to be appropriately addressed in the context of viability and food safety. Indeed, long-term and inappropriate storage of seeds might result in enhancement of protein glycation, which might affect their quality and longevity. Glycation of seed proteins can be probed by exhaustive acid hydrolysis and quantification of the glycation adduct Nɛ-(carboxymethyl)lysine (CML) by liquid chromatography-mass spectrometry (LC-MS). This approach, however, does not allow analysis of thermally and chemically labile glycation adducts, like glyoxal-, methylglyoxal- and 3-deoxyglucosone-derived hydroimidazolones. Although enzymatic hydrolysis might be a good solution in this context, it requires aqueous conditions, which cannot ensure reconstitution of seed protein isolates. Because of this, the complete profiles of seed advanced glycation end products (AGEs) are not characterized so far. Therefore, here we propose the approach, giving access to quantitative solubilization of seed proteins in presence of sodium dodecyl sulfate (SDS) and their quantitative enzymatic hydrolysis prior to removal of SDS by reversed phase solid phase extraction (RP-SPE). Using methylglyoxal-derived hydroimidazolone 1 (MG-H1) as a case example, we demonstrate the applicability of this method for reliable and sensitive LC-MS-based quantification of chemically labile AGEs and its compatibility with bioassays.
Culture Dependent and Independent Analysis of Potential Probiotic Bacterial Genera and Species Present in the Phyllosphere of Raw Eaten Produce
Authors: Patz Sascha , Witzel Katja , Scherwinski Ann-Christin , Ruppel Silke
Published: July 2019

The plant phyllosphere is colonized by a complex ecosystem of microorganisms. Leaves of raw eaten vegetables and herbs are habitats for bacteria important not only to the host plant, but also to human health when ingested via meals. The aim of the current study was to determine the presence of putative probiotic bacteria in the phyllosphere of raw eaten produce. Quantification of bifidobacteria showed that leaves of Lepidium sativum L., Cichorium endivia L., and Thymus vulgaris L. harbor between 103 and 106 DNA copies per gram fresh weight. Total cultivable bacteria in the phyllosphere of those three plant species ranged from 105 to 108 CFU per gram fresh weight. Specific enrichment of probiotic lactic acid bacteria from C. endivia, T. vulgaris, Trigonella foenum-graecum L., Coriandrum sativum L., and Petroselinum crispum L. led to the isolation of 155 bacterial strains, which were identified as Pediococcus pentosaceus, Enterococcus faecium, and Bacillus species, based on their intact protein pattern. A comprehensive community analysis of the L. sativum leaves by PhyloChip hybridization revealed the presence of genera Bifidobacterium, Lactobacillus, and Streptococcus. Our results demonstrate that the phyllosphere of raw eaten produce has to be considered as a substantial source of probiotic bacteria and point to the development of vegetables and herbs with added probiotic value.
Additive Pharmacological Interaction between Cisplatin (CDDP) and Histone Deacetylase Inhibitors (HDIs) in MDA-MB-231 Triple Negative Breast Cancer (TNBC) Cells with Altered Notch1 Activity—An Isobolographic Analysis
Authors: Wawruszak Anna , Luszczki Jarogniew J. , Kalafut Joanna , Okla Karolina , Halasa Marta , Rivero-Muller Adolfo , Stepulak Andrzej
Published: July 2019

The aim of this study was to investigate the influence of the Notch1 activity level on the pharmacological interaction between cisplatin (CDDP) and two histone deacetylase inhibitors (HDIs)—valproic acid (VPA) and vorinostat (SAHA) in the triple negative breast cancer (TNBC) cells. Stable breast cancer (BC) cell lines with increased and decreased activity of Notch1 were generated using a transfection method. The type of interaction between CDDP and the HDIs was determined by isobolographic analysis of cell proliferation in MDA-MB-231 cells with differential levels of Notch1 activity in vitro. The combination of CDDP/SAHA and CDDP/VPA in the MDA-MB-231 triple negative breast cancer (TNBC) cells with increased activity of Notch1, as well as CDDP/VPA in the MDA-MB-231 cells with decreased activity of Notch1, yielded an additive interaction, whereas additivity with a tendency towards antagonism was observed for the combination of CDDP/SAHA in MDA-MB-231 cells with the decreased activity of Notch1. Our studies demonstrated that SAHA and VPA might be considered as potential therapeutic agents in combination therapy with CDDP against TNBC with altered Notch1 activity.
Asymmetric (ADMA) and Symmetric (SDMA) Dimethylarginines in Chronic Kidney Disease: A Clinical Approach
Authors: Oliva-Damaso Elena , Oliva-Damaso Nestor , Rodriguez-Esparragon Francisco , Payan Juan , Baamonde-Laborda Eduardo , Gonzalez-Cabrera Fayna , Santana-Estupiñan Raquel , Rodriguez-Perez Jose Carlos
Published: July 2019

Asymmetric dimethylarginine (ADMA) and its enantiomer, Symmetric dimethylarginine (SDMA), are naturally occurring amino acids that were first isolated and characterized in human urine in 1970. ADMA is the most potent endogenous inhibitor of nitric oxide synthase (NOS), with higher levels in patients with end-stage renal disease (ESRD). ADMA has shown to be a significant predictor of cardiovascular outcome and mortality among dialysis patients. On the other hand, although initially SDMA was thought to be an innocuous molecule, we now know that it is an outstanding marker of renal function both in human and in animal models, with ESRD patients on dialysis showing the highest SDMA levels. Today, we know that ADMA and SDMA are not only uremic toxins but also independent risk markers for mortality and cardiovascular disease (CVD). In this review, we summarize the role of both ADMA and SDMA in chronic kidney disease along with other cardiovascular risk factors.
Glutathione Metabolism in Renal Cell Carcinoma Progression and Implications for Therapies
Authors: Xiao Yi , Meierhofer David
Published: July 2019

A significantly increased level of the reactive oxygen species (ROS) scavenger glutathione (GSH) has been identified as a hallmark of renal cell carcinoma (RCC). The proposed mechanism for increased GSH levels is to counteract damaging ROS to sustain the viability and growth of the malignancy. Here, we review the current knowledge about the three main RCC subtypes, namely clear cell RCC (ccRCC), papillary RCC (pRCC), and chromophobe RCC (chRCC), at the genetic, transcript, protein, and metabolite level and highlight their mutual influence on GSH metabolism. A further discussion addresses the question of how the manipulation of GSH levels can be exploited as a potential treatment strategy for RCC.
Heme, Heme Oxygenase, and Endoplasmic Reticulum Stress—A New Insight into the Pathophysiology of Vascular Diseases
Authors: Gáll Tamás , Balla György , Balla József
Published: July 2019

The prevalence of vascular disorders continues to rise worldwide. Parallel with that, new pathophysiological pathways have been discovered, providing possible remedies for prevention and therapy in vascular diseases. Growing evidence suggests that endoplasmic reticulum (ER) stress is involved in a number of vasculopathies, including atherosclerosis, vascular brain events, and diabetes. Heme, which is released from hemoglobin or other heme proteins, triggers various pathophysiological consequence, including heme stress as well as ER stress. The potentially toxic free heme is converted by heme oxygenases (HOs) into carbon monoxide (CO), iron, and biliverdin (BV), the latter of which is reduced to bilirubin (BR). Redox-active iron is oxidized and stored by ferritin, an iron sequestering protein which exhibits ferroxidase activity. In recent years, CO, BV, and BR have been shown to control cellular processes such as inflammation, apoptosis, and antioxidant defense. This review covers our current knowledge about how heme induced endoplasmic reticulum stress (HIERS) participates in the pathogenesis of vascular disorders and highlights recent discoveries in the molecular mechanisms of HO-mediated cytoprotection in heme stress and ER stress, as well as crosstalk between ER stress and HO-1. Furthermore, we focus on the translational potential of HIERS and heme oxygenase-1 (HO-1) in atherosclerosis, diabetes mellitus, and brain hemorrhage.
GARP as an Immune Regulatory Molecule in the Tumor Microenvironment of Glioblastoma Multiforme
Authors: Zimmer Niklas , Kim Ella , Schupp Jonathan , Sprang Bettina , Leukel Petra , Khafaji Fatemeh , Ringel Florian , Sommer Clemens , Tuettenberg Jochen , Tuettenberg Andrea
Published: July 2019

Glycoprotein A repetition predominant (GARP), a specific surface molecule of activated regulatory T cells, has been demonstrated to significantly contribute to tolerance in humans by induction of peripheral Treg and regulatory M2-macrophages and by inhibition of (tumorantigen-specific) T effector cells. Previous work identified GARP on Treg, and also GARP on the surface of several malignant tumors, as well as in a soluble form being shedded from their surface, contributing to tumor immune escape. Preliminary results also showed GARP expression on brain metastases of malignant melanoma. On the basis of these findings, we investigated whether GARP is also expressed on primary brain tumors. We showed GARP expression on glioblastoma (GB) cell lines and primary GB tissue, as well as on low-grade glioma, suggesting an important influence on the tumor micromilieu and the regulation of immune responses also in primary cerebral tumors. This was supported by the finding that GB cells led to a reduced, in part GARP-dependent effector T cell function (reduced proliferation and reduced cytokine secretion) in coculture experiments. Interestingly, GARP was localized not only on the cell surface but also in the cytoplasmatic, as well as nuclear compartments in tumor cells. Our findings reveal that GARP, as an immunoregulatory molecule, is located on, as well as in, tumor cells of GB and low-grade glioma, inhibiting effector T cell function, and thus contributing to the immunosuppressive tumor microenvironment of primary brain tumors. As GARP is expressed on activated Treg, as well as on brain tumors, it may be an interesting target for new immunotherapeutic approaches using antibody-based strategies as this indication.
Crowdsourcing the Paldaruo Speech Corpus of Welsh for Speech Technology
Authors: Cooper Sarah , Jones Dewi Bryn , Prys Delyth
Published: July 2019

Collecting speech data for a low-resource language is challenging when funding and resources are limited. This paper describes the process of designing, creating and using the Paldaruo Speech Corpus for developing speech technology for Welsh. Specifically, this paper focuses on the crowdsourcing of data using an app on smartphones and mobile devices, allowing speakers from across Wales to contribute. We discuss the development of reading prompts: isolated words and full sentences, as well as the metadata collected from contributors. We also provide background on the design of the Paldaruo App as well as the main uses for the corpus and its availability and licensing. The corpus was designed for the development of speech recognition for Welsh and has been used to create a number of other resources. These methods can be extended to other languages, and suggestions for other low-resource languages are discussed.
Using Gamma Irradiated Galleria mellonella L. and Plodia interpunctella (Hübner) Larvae to Optimize Mass Rearing of Parasitoid Habrobracon hebetor (Say) (Hymenoptera: Braconidae)
Authors: Hasan Md. Mahbub , Yeasmin Lubna , Athanassiou Christos G. , Bari Md. Abdul , Islam Md. Saiful
Published: July 2019

We evaluated possible improvements to the mass rearing of the larval parasitoid Habrobracon hebetor (Say) (Hymenoptera: Braconidae) on irradiated host wax moth Galleria mellonella L. and Indian meal moth Plodia interpunctella (Hübner) (Lepidoptera: Pyralidae) larvae. The use of irradiated G. mellonella and P. interpunctella larvae at the dose of 150 Gy proved useful for enhancing the parasitism and adult emergence of H. hebetor due to the absence of negative repercussions on parasitoid development. Overall, parasitism was increased as the host larvae was irradiated with higher doses, while significantly higher parasitism was recorded at 150 and 300 Gy compared to lower doses. The female parasitoids preferred the irradiated larvae and significantly higher numbers of larvae were parasitized compared with non-irradiated larvae. The results also showed that irradiated larvae of G. mellonella served better as hosts for H. hebetor as compared with irradiated larvae of P. interpunctella. The implementation of these findings would be helpful for improving the mass production of parasitoids and the effectiveness of releases of biocontrol agents for the control of stored product pests.
Dynamics of Aboveground Natural Enemies of Grasshoppers, and Biodiversity after Application of Paranosema locustae in Rangeland
Authors: Shi Wang-Peng , Wang Xiao-Yu , Yin Yue , Zhang Yu-Xing , Rizvi Um-e-Hani , Tan Shu-Qian , Cao Chuan , Yu Hong-Yan , Ji Rong
Published: July 2019

Substantial harm to ecosystems from the use of chemical pesticides has led to an increasing interest in the use of biopesticides to control grasshoppers in rangelands, including China. One such potential biopesticide for control of grasshoppers is the fungus Paranosema locustae. In this study, the dynamics of aboveground natural enemies of grasshoppers and arthropod diversity 0–9 years after application of P. locustae were investigated in rangeland in Qinghai Plateau, China. We found that the number of species and of individuals of aboveground natural enemies increased by 17–250% and 40–126%, respectively, after spraying P. locustae, and that the main natural enemies showed three peaks after treatment. The conventional indices of species diversity (H’) and evenness (J’) increased by 11–267% and 13–171%, respectively, after treatment with P. locustae. The results showed the positive effects of P. locustae on aboveground natural enemies and biodiversity in an arthropod community in Chinese rangeland. Paranosema locustae is thought to be a safe biological control agent for grasshopper management in Northwestern China.
The Mediating Effects of Affect on Associations between Impulsivity or Resilience and Internet Gaming Disorder
Authors: Shin Daun , Choi A , Lee Jiyoon , Chung Sun , Kim Bomi , Park Minkyung , Jung Myung , Kim Dai , Choi Jung-Seok
Published: July 2019

Internet gaming disorder (IGD) is a new disease proposed by the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5), and has been studied extensively in relation to depression and impulsivity. The relationship between resilience and disease has been found in a variety of addictive disorders, but studies on IGD are lacking. In this study, 71 IGD patients and 78 healthy controls (HCs) were recruited. Impulsivity, resilience, affects, and the degree of internet game addiction were measured using formal tools. The measured values were analyzed by mediation analysis to evaluate the mediating role of affects on resilience and impulsivity related to IGD symptoms. The IGD group showed higher impulsivity, lower resilience, lower positive affect, and higher negative affect than the HC group. The mediation analysis showed that a positive affect was a mediator between impulsivity and the severity of addiction in both groups. Negative affect mediated impulsivity/resilience and the severity of addiction only in the IGD group. Although the results of this study are based on a narrow category of subjects, who are young male adults around 25 years of age, the results suggest that positive affect can be strengthened to prevent the IGD illness, and that illness symptoms may be alleviated by reducing negative affect.
Total Intravenous Anesthesia Maintained the Degree of Pre-Existing Mitral Regurgitation Better than Isoflurane Anesthesia in Cardiac Surgery: A Randomized Controlled Trial
Authors: Ahn Jin Hee , Ahn Hyun Joo , Yi Jae-Woo
Published: July 2019

Accurate assessment of mitral regurgitation (MR) is critical during mitral valve repair surgery. However, anesthesia may influence the degree of mitral regurgitation by changing pre- and after-load or cardiac contractility. Therefore, we compared changes in mitral regurgitation by total intravenous anesthesia (TIVA) and inhalation anesthesia in patients with pre-existing mitral regurgitation. This was a double-blind randomized controlled study conducted at a tertiary care center in 2018. Fifty-four mitral regurgitation patents undergoing elective cardiac surgery were randomly assigned to receive TIVA or isoflurane. Primary endpoint was change of regurgitation volume by anesthesia. The reduction of regurgitation volume by anesthesia was greater in the isoflurane group than in the TIVA group (mean (95% confidence interval CI): −0.20 (−6.15, 5.75) vs. −9.66 (−15.77, −3.56), mL·beat−1, p = 0.0266) and this phenomenon was more prominent with severe mitral regurgitation (grade 3 or 4) (mean (95% CI): −0.33 (−9.10, 8.44) vs. −16.20 (−24.22, −8.18), mL·beat−1, p = 0.0079). Among patients with MR grade 3 or 4, 94% remained the same with TIVA during anesthesia compared to 56% with isoflurane. In conclusion, TIVA maintained the pre-anesthetic state of mitral regurgitation relatively well, while the severity of mitral regurgitation tended to decrease with isoflurane anesthesia.
Decreased Level of Blood MicroRNA-133b in Men with Opioid Use Disorder on Methadone Maintenance Therapy
Authors: Hsu Chih-Wei , Huang Tiao-Lai , Tsai Meng-Chang
Published: July 2019

Although previous animal studies have indicated that certain micro ribonucleic acids (microRNAs) play a part in the pathway of opioid addiction, whether such findings extend to human models is yet unknown. This study aims to investigate the important microRNA expressions in patients with opioid use disorder (OUD) on methadone maintenance treatment (MMT) compared to healthy controls and analyze the correlation between microRNAs and opioid characteristics among the patients. We recruited 50 patients and 25 controls, and both groups were matched regarding gender, age, and body mass index. Serum microRNAs (miR-133b, miR-23b, miR-190, miR-206, miR-210, and miR-21) were measured. The age of OUD onset, duration of MMT participation, and recent daily methadone dosage were considered the opioid characteristics. We adopted the t-test to compare the difference between patients and controls and Pearson’s correlation to evaluate the association between microRNAs and opioid profiles. Only the level of miR-133b in OUD patients on MMT was significantly lower than that in healthy controls. We did not detect differences of any other microRNA expressions between the two groups. Furthermore, we found no evidence to support the association between microRNAs and opioid characteristics. This study indicates that miR-133b values may be decreased in OUD patients on MMT.
Association between Thyroid-Stimulating Hormone Level after Total Thyroidectomy and Hypercholesterolemia in Female Patients with Differentiated Thyroid Cancer: A Retrospective Study
Authors: Lee Young Ki , Lee Hokyou , Han Seunghee , Jung Hyein , Shin Dong Yeob , Nam Kee-Hyun , Chung Woong Youn , Lee Eun Jig
Published: July 2019

Less-intense TSH suppression strategies can be used for differentiated thyroid cancer (DTC) patients with a low recurrence risk, but their metabolic outcomes are not well known. We aimed to evaluate changes in the serum cholesterol levels and the risk of hypercholesterolemia according to postoperative TSH levels in 1092 female DTC patients receiving levothyroxine after total thyroidectomy. The preoperative-to-follow-up change in total cholesterol (TC) levels in the TSH level <0.03, 0.03–0.3, 0.3–2, and 2–5 mIU/L groups was −3.69 mg/dL (p = 0.006), +0.13 mg/dL (p = 0.926), +12.46 mg/dL (p < 0.001), and +16.46 mg/dL (p < 0.001), respectively. When compared with TSH levels of 0.03–0.3 mIU/L, those of 0.3–2 mIU/L were found to be associated with hypercholesterolemia (adjusted odds ratio (AOR) = 1.86 and 5.08 for TC 200–240 and ≥240 vs. <200 mg/dL) and hyper-low-density lipoprotein (LDL)-cholesterolemia (AOR = 2.76 for LDL-cholesterol ≥160 vs. <130 mg/dL). Additionally, TSH levels of 2–5 mIU/dL were associated with hypercholesterolemia (AOR = 2.85 and 6.95 for TC 200–240 and ≥240 vs. <200 mg/dL) and hyper-LDL-cholesterolemia (AOR = 2.08 and 4.17 for LDL-cholesterol 130–159 and ≥160 mg/dL vs. <130 mg/dL). In patients with normal TSH level maintenance following thyroidectomy, TC levels markedly increased, resulting in an increased hypercholesterolemia prevalence. Metabolic derangement risk due to insufficient levothyroxine replacement should be considered in the adoption of less-intense TSH suppression strategies, postoperatively, in DTC patients.
Emerging and Novel Treatments for Pituitary Tumors
Authors: Ilie Mirela Diana , Lasolle Hélène , Raverot Gérald
Published: July 2019

A subset of pituitary neuroendocrine tumors (PitNETs) have an aggressive behavior, showing resistance to treatment and/or multiple recurrences in spite of the optimal use of standard therapies (surgery, conventional medical treatments, and radiotherapy). To date, for aggressive PitNETs, temozolomide (TMZ) has been the most used therapeutic option, and has resulted in an improvement in the five-year survival rate in responders. However, given the fact that roughly only one third of patients showed a partial or complete radiological response on the first course of TMZ, and even fewer patients responded to a second course of TMZ, other treatment options are urgently needed. Emerging therapies consist predominantly of peptide receptor radionuclide therapy (20 cases), vascular endothelial growth factor receptor-targeted therapy (12 cases), tyrosine kinase inhibitors (10 cases), mammalian target of rapamycin (mTOR) inhibitors (six cases), and more recently, immune checkpoint inhibitors (one case). Here, we present the available clinical cases published in the literature for each of these treatments. The therapies that currently show the most promise (based on the achievement of partial radiological response in a certain number of cases) are immune checkpoint inhibitors, peptide receptor radionuclide therapy, and vascular endothelial growth factor receptor-targeted therapy. In the future, further improvement of these therapies and the development of other novel therapies, their use in personalized medicine, and a better understanding of combination therapies, will hopefully result in better outcomes for patients bearing aggressive PitNETs.
Short-Term Proton Pump Inhibitor Use and Hepatic Encephalopathy Risk in Patients with Decompensated Cirrhosis
Authors: Kuan Yi-Chun , Huang Kuang-Wei , Lin Cheng-Li , Luo Jiing-Chyuan , Kao Chia-Hung
Published: July 2019

Objective: A window period of approximately 3–6 months is usually adopted in studies that evaluate hepatic encephalopathy (HE) risk in proton pump inhibitor (PPI) users. However, HE risk after short-term PPI exposure remains unclear. We explored the effect of short-term PPI exposure using a case-crossover study design. Design: Records of patients with decompensated cirrhosis who had received an HE diagnosis were retrieved from the National Health Insurance Research Database. PPI use rates were compared for case and control with window periods of 7, 14, and 28 days. The adjusted self-matched odds ratio (OR) and 95% confidence interval (CI) from a conditional logistic regression model were used to determine the association between PPI use and HE risk. Results: Overall, 13 195 patients were analyzed. The adjusted OR for HE risk after PPI exposure was 3.13 (95% CI = 2.33–4.20) for the 7-day window, 4.77 (95% CI = 3.81–5.98) for the 14-day window, and 5.60 (95% CI = 4.63–6.78) for the 28-day window. All PPI categories, except omeprazole and pantoprazole, were associated with an increased HE risk. Irrespective of other precipitating factors, such as recent gastrointestinal bleeding or infection, PPI significantly increased HE risk. Conclusion: Short-term PPI use is significantly associated with HE in patients with decompensated cirrhosis. Physicians should use PPI in these patients for appropriate indications, and carefully monitor signs of HE even after short-term exposure. Owing to the limitations of retrospective design in the current study, further study is warranted to confirm our findings.
Inflammation as a Therapeutic Target in Atherosclerosis
Authors: Nguyen Mau , Fernando Sanuja , Schwarz Nisha , Tan Joanne , Bursill Christina , Psaltis Peter
Published: July 2019

Atherosclerotic coronary artery disease (CAD) results from build-up of cholesterol-rich plaques in the walls of the coronary arteries and is a leading cause of death. Inflammation is central to atherosclerosis. Uncontrolled inflammation makes coronary plaques “unstable” and vulnerable to rupture or erosion, leading to thrombosis and myocardial infarction (MI). As multiple inflamed plaques often co-exist in the coronary system, patients are at risk of repeated atherothrombotic cardiovascular events after MI, with rates of 10–12% at one year and 18–20% at three years. This is largely because current therapies for CAD, such as lipid-lowering statins, do not adequately control plaque inflammation. New anti-atherosclerotic agents are therefore needed, especially those that better target inflammation. The recent positive results for the anti-interleukin-1-beta (IL-1β) monoclonal antibody, Canakinumab, in the Canakinumab Anti-inflammatory Thrombosis Outcome Study (CANTOS) clinical trial has provided a major stimulant to the field. It highlights that not only is inflammation important from a pathogenic and risk prediction perspective in CAD, but that reducing inflammation can be beneficial. The challenge is now to find the best strategies to achieve this in real-world practice. This review outlines the role that inflammation plays in atherosclerosis and provides an update on anti-inflammatory therapies currently being investigated to target atherosclerosis.
Serum Alkaline Phosphatase as a Predictor of Cardiac and Cerebrovascular Complications after Lumbar Spinal Fusion Surgery in Elderly: A Retrospective Study
Authors: You Ann Hee , Han Dong Woo , Ham Sung Yeon , Lim Wonsik , Song Young
Published: July 2019

We retrospectively enrolled 1395 patients aged > 65 years undergoing posterior lumbar spinal fusion surgery and classified them into tertiles based on serum Alkaline Phosphatase (ALP) levels (<63, 63–79, >79 IU/L). The primary outcome was the incidence of 30-day major adverse cardiac and cerebrovascular events (MACCE; composite endpoint defined as the occurrence of ≥1 of the following events: new-onset myocardial infarction, stroke, or cardiovascular mortality). The incidence of the composite endpoint was the highest in the third serum ALP tertile (0.4% vs. 0.2% vs. 2.2% in the first, second, and third tertile, respectively, p = 0.003). Multivariate analysis showed that the third serum ALP tertile was an independent predictor of the composite endpoint of MACCE (odds ratio 4.507, 95% confidence interval 1.378–14.739, p = 0.013). The optimal cut-off value of preoperative serum ALP showing the best discriminatory capacity to predict postoperative MACCE (measured by receiver-operating characteristic curve analysis) was 83 IU/L (area under curve 0.694, 95% confidence interval 0.574–0.813, p = 0.016). Preoperative serum ALP levels were independently associated with the composite endpoint of postoperative 30-days MACCE. We suggest that serum ALP can be used as a biomarker to predict cardiac and cerebrovascular complications following lumbar spinal fusion surgery in elderly patients.
Holographic Three-Dimensional Imaging of Terra-Cotta Warrior Model Using Fractional Fourier Transform
Authors: Gao Zhi-Fang , Zheng Hua-Dong , Yu Ying-Jie
Published: July 2019

Holographic three-dimensional (3D) imaging of Terra-Cotta Warrior model using Fractional Fourier Transform is introduced in this paper. Phase holograms of Terra-Cotta Warrior model are calculated from 60 horizontal viewing-angles by the use of fractional Fourier transform (FRT). Multiple phase holograms are calculated for each angle by adding proper pseudorandom phase to reduce the speckle noise of a reconstructed image. Experimental system based on high-resolution phase-only spatial light modulator (SLM) is built for 3D image reconstruction from the calculated phase holograms. The texture of the Terra-Cotta Warrior model is rough. The calculation of rough texture is optimized in order to show better model details. The effects of computing distance and layer thickness on imaging quality are analyzed finally.
Editorial for Special Issue: “Livelihood and Landscape Change in Africa: Future Trajectories for Improved Well-Being under a Changing Climate”
Authors: Shackleton Sheona , Masterson Vanessa , Hebinck Paul , Speranza Chinwe Ifejika , Spear Dian , Tengö Maria
Published: July 2019

Rural people’s livelihoods are intimately linked to the landscapes in which they live and are particularly vulnerable to changes in these landscapes (Suich et al [...]
Using Eye-Movements to Track Bilingual Activation
Authors: Martínez-García María Teresa
Published: July 2019

Recent research found that the languages of bilingual listeners are active and interact, such that both lexical representations are activated by the spoken input with which they are compatible. However, the time course of bilingual activation and whether suprasegmental information further modulates this cross-language competition are still not well understood. This study investigates the effect of stress placement on the processing of English–Spanish cognates by beginner-to-intermediate Spanish-speaking second-language (L2) learners of English and intermediate-to-advanced English-speaking L2 learners of Spanish using the visual-world eye-tracking paradigm. In each trial, participants saw a target (asado, ‘roast’), one of two competitors (stress match: asados, ‘roast (pl)’; stress mismatch: asador, ‘rotisserie’), and two unrelated distracters, while hearing the target word. The experiment included a non-cognate condition (asado-asados-asador) and a cognate condition, where the stress pattern of the English word corresponding to the Spanish competitor in the stress-mismatch condition (inventor) instead matched that of the Spanish target (invento, ‘invent’). Growth-curve analyses revealed cognate-status and stress-mismatch effects for Spanish-speaking L2 learners of English, and cognate-status and stress-mismatch effects, and an interaction for English-speaking L2 learners of Spanish. This suggests that both groups use stress for word recognition, but the English stress pattern only affects the processing of Spanish words in the English-speaking L2 learners of Spanish.
New Applications of High-Resolution Analytical Methods to Study Trace Organic Compounds in Extraterrestrial Materials
Authors: Naraoka Hiroshi , Hashiguchi Minako , Sato Yu , Hamase Kenji
Published: July 2019

Organic compounds are present as complex mixtures in extraterrestrial materials including meteorites, which may have played important roles in the origin of life on the primitive Earth. However, the distribution and formation mechanisms of meteoritic organic compounds are not well understood, because conventional analytical methods have limited resolution and sensitivity to resolve their molecular complexity. In this study, advanced instrumental development and analyses are proposed in order to study the trace organic compounds of extraterrestrial materials: (1) a clean room environment to avoid organic contamination during analysis; (2) high-mass-resolution analysis (up to ~150,000 m/Δm) coupled with high-performance liquid chromatography (HPLC) in order to determine the elemental composition using exact mass for inferring the chemical structure; (3) superior chromatographic separation using a two-dimensional system in order to determine the structural and optical isomers of amino acids; and (4) in situ organic compound analysis and molecular imaging of the sample surface. This approach revealed a higher complexity of organic compounds with a heterogeneous distribution in meteorites. These new methods can be applied to study the chemical evolution of meteoritic organic compounds as well as the molecular occurrence in very-low-mass extraterrestrial materials such as asteroid-returned samples.
Improvement of the Tribological Characteristics of AISI 8620, 8640 and 52100 Steels through Thermo-Reactive Treatments
Authors: Triani Rafael Magalhães , Mariani Fábio Edson , Gomes Lucas Fuscaldi De Assis , De Oliveira Pedro Gabriel Bonella , Totten George Edward , Casteletti Luiz Carlos
Published: July 2019

The production of vanadium and niobium carbides (VC and NbC) layers on AISI 8620, 8640, and 52100 steels may increase hardness and wear resistance of substrates. Thermochemical treatments were performed at 1000 °C for 2 and 4 h. The characterization of the treated samples was carried out by means of Knoop microhardness tests, “calotest” type microadhesive wear test, layer adhesion test according to VDI 3198 standard, and X-ray diffraction. Compact and uniform layers of VC and NbC were obtained in all treatments, with hardness up to 2500 HK and microadhesive wear resistance far superior to that of the substrates, indicating the great efficiency of these treatments for tribological applications.
Experimental Research on Uniaxial Compression Constitutive Model of Hybrid Fiber-Reinforced Cementitious Composites
Authors: Cui Tao , He Haoxiang , Yan Weiming
Published: July 2019

In order to establish accurate compressive constitutive model of Hybrid Fiber-Reinforced Concrete (HFRC), 10 groups of HFRC specimens containing polyvinyl alcohol (PVA), polypropylene (PP), and steel fibers are designed and compressive testing is conducted. On the basis of summarizing and comparing the existing research, accuracy of various stress-strain constitutive model is compared and the method of calculating fitting parameters is put forward, peak stress, peak strain, and elastic modulus of specimens with different fiber proportion are analyzed, the calculation expressions of each fitting parameter are given. The results show that, under the condition that the volume of the hybrid fiber is 2% with the proportion of the steel fiber increase, the strength of the specimen increases, the peak strain decreases slightly, and the elastic modulus increases significantly. In specimens mixed with PVA-PP hybrid fiber, with the increase of PVA fiber proportion, the peak stress and elastic modulus of the material are improved, and the peak strain are decreased. The existing stress-strain expressions agree well with the tests. Accuracy of exponential model proposed in this paper is the highest, which can be applied in engineering and nonlinear finite element analysis of components.
A Nondestructive Indirect Approach to Long-Term Wood Moisture Monitoring Based on Electrical Methods
Authors: Slávik Richard , Čekon Miroslav , Štefaňák Jan
Published: July 2019

Wood has a long tradition of use as a building material due its properties and availability. However, it is very sensitive to moisture. Wood components of building structures basically require a certain level of moisture protection, and thus moisture monitoring to ensure the serviceability of such components during their whole lifespan while integrated within buildings is relevant to this area. The aim of this study is to investigate two moisture monitoring techniques promoting moisture safety in wood-based buildings (i.e., new structures, as well as renovated and protected buildings). The study is focused on the comparison of two electrical methods that can be employed for the nondestructive moisture monitoring of wood components integrated in the structures of buildings. The main principle of the two presented methods of the moisture measurement by electric resistance is based on a simple resistor–capacitor (RC) circuit system improved with ICM7555 chip and integrator circuit using TLC71 amplifier. The RC-circuit is easier to implement thanks to the digital signals of the used chip, whilst the newly presented integration method allows faster measurement at lower moisture contents. A comparative experimental campaign utilizing spruce wood samples is conducted in this relation. Based on the results obtained, both methods can be successfully applied to wood components in buildings for moisture contents above 8%.
Biological Scaffolds for Abdominal Wall Repair: Future in Clinical Application?
Authors: Costa Alessandra , Adamo Sergio , Gossetti Francesco , D’Amore Linda , Ceci Francesca , Negro Paolo , Bruzzone Paolo
Published: July 2019

Millions of abdominal wall repair procedures are performed each year for primary and incisional hernias both in the European Union and in the United States with extremely high costs. Synthetic meshes approved for augmenting abdominal wall repair provide adequate mechanical support but have significant drawbacks (seroma formation, adhesion to viscera, stiffness of abdominal wall, and infection). Biologic scaffolds (i.e., derived from naturally occurring materials) represent an alternative to synthetic surgical meshes and are less sensitive to infection. Among biologic scaffolds, extracellular matrix scaffolds promote stem/progenitor cell recruitment in models of tissue remodeling and, in the specific application of abdominal wall repair, have enough mechanical strength to support the repair. However, many concerns remain about the use of these scaffolds in the clinic due to their higher cost of production compared with synthetic meshes, despite having the same recurrence rate. The present review aims to highlight the pros and cons of using biologic scaffolds as surgical devices for abdominal wall repair and present possible improvements to widen their use in clinical practice.
MnO2@Corncob Carbon Composite Electrode and All-Solid-State Supercapacitor with Improved Electrochemical Performance
Authors: Li Xin-Sheng , Xu Man-Man , Yang Yang , Huang Quan-Bo , Wang Xiao-Ying , Ren Jun-Li , Wang Xiao-Hui
Published: July 2019

Two corncob-derived carbon electrode materials mainly composed of micropores (activated carbon, AC) and mesopores/macropores (corncob carbon, CC) were prepared and studied after the anodic electrodeposition of MnO2. The capacity of the MnO2/activated carbon composite (MnO2@AC) electrode did not noticeably increase after MnO2 electrodeposition, while that of the MnO2/corncob carbon composite (MnO2@CC) electrode increased up to 9 times reaching 4475 mF cm−2. An asymmetric all-solid-state supercapacitor (ASC) was fabricated using AC as the anode, MnO2@CC as the cathode, and polyvinyl alcohol (PVA)/LiCl gel as the electrolyte. An ultrahigh specific capacitance of 3455.6 mF cm−2 at 1 mA cm−2, a maximum energy density of 1.56 mW h cm−2, and a long lifetime of 10,000 cycles can be achieved. This work provides insights in understanding the function of MnO2 in biomass-derived electrode materials, and a green path to prepare an ASC from waste biomass with excellent electrochemical performance.