bluuebunny/crossref_metadata_2025 huggingface dataset:
The Diagnostic Value of Mir-133a in ST Elevation and Non-ST Elevation Myocardial Infarction: A Meta-Analysis
Authors: Wexler Yehuda , Nussinovitch Udi
Published: April 2020

Numerous studies have reported correlations between plasma microRNA signatures and cardiovascular disease. MicroRNA-133a (Mir-133a) has been researched extensively for its diagnostic value in acute myocardial infarction (AMI). While initial results seemed promising, more recent studies cast doubt on the diagnostic utility of Mir-133a, calling its clinical prospects into question. Here, the diagnostic potential of Mir-133a was analyzed using data from multiple papers. Medline, Embase, and Web of Science were systematically searched for publications containing “Cardiovascular Disease”, “MicroRNA”, “Mir-133a” and their synonyms. Diagnostic performance was assessed using area under the summary receiver operator characteristic curve (AUC), while examining the impact of age, sex, final diagnosis, and time. Of the 753 identified publications, 9 were included in the quantitative analysis. The pooled AUC for Mir-133a was 0.73. Analyses performed separately on studies using healthy vs. symptomatic controls yielded pooled AUCs of 0.89 and 0.68, respectively. Age and sex were not found to significantly affect diagnostic performance. Our findings indicate that control characteristics and methodological inconsistencies are likely the causes of incongruent reports, and that Mir-133a may have limited use in distinguishing symptomatic patients from those suffering AMI. Lastly, we hypothesized that Mir-133a may find a new use as a risk stratification biomarker in patients with specific subsets of non-ST elevation myocardial infarction (NSTEMI).
Circulating Small Noncoding RNAs Have Specific Expression Patterns in Plasma and Extracellular Vesicles in Myelodysplastic Syndromes and Are Predictive of Patient Outcome
Authors: Hrustincova Andrea , Krejcik Zdenek , Kundrat David , Szikszai Katarina , Belickova Monika , Pecherkova Pavla , Klema Jiri , Vesela Jitka , Hruba Monika , Cermak Jaroslav , Hrdinova Tereza , Krijt Matyas , Valka Jan , Jonasova Anna , Dostalova Merkerova Michaela
Published: April 2020

Myelodysplastic syndromes (MDS) are hematopoietic stem cell disorders with large heterogeneity at the clinical and molecular levels. As diagnostic procedures shift from bone marrow biopsies towards less invasive techniques, circulating small noncoding RNAs (sncRNAs) have become of particular interest as potential novel noninvasive biomarkers of the disease. We aimed to characterize the expression profiles of circulating sncRNAs of MDS patients and to search for specific RNAs applicable as potential biomarkers. We performed small RNA-seq in paired samples of total plasma and plasma-derived extracellular vesicles (EVs) obtained from 42 patients and 17 healthy controls and analyzed the data with respect to the stage of the disease, patient survival, response to azacitidine, mutational status, and RNA editing. Significantly higher amounts of RNA material and a striking imbalance in RNA content between plasma and EVs (more than 400 significantly deregulated sncRNAs) were found in MDS patients compared to healthy controls. Moreover, the RNA content of EV cargo was more homogeneous than that of total plasma, and different RNAs were deregulated in these two types of material. Differential expression analyses identified that many hematopoiesis-related miRNAs (e.g., miR-34a, miR-125a, and miR-150) were significantly increased in MDS and that miRNAs clustered on 14q32 were specifically increased in early MDS. Only low numbers of circulating sncRNAs were significantly associated with somatic mutations in the SF3B1 or DNMT3A genes. Survival analysis defined a signature of four sncRNAs (miR-1237-3p, U33, hsa_piR_019420, and miR-548av-5p measured in EVs) as the most significantly associated with overall survival (HR = 5.866, p < 0.001). In total plasma, we identified five circulating miRNAs (miR-423-5p, miR-126-3p, miR-151a-3p, miR-125a-5p, and miR-199a-3p) whose combined expression levels could predict the response to azacitidine treatment. In conclusion, our data demonstrate that circulating sncRNAs show specific patterns in MDS and that their expression changes during disease progression, providing a rationale for the potential clinical usefulness of circulating sncRNAs in MDS prognosis. However, monitoring sncRNA levels in total plasma or in the EV fraction does not reflect one another, instead, they seem to represent distinctive snapshots of the disease and the data should be interpreted circumspectly with respect to the type of material analyzed.
Salivary Histatin 1 and 2 Are Targeted to Mitochondria and Endoplasmic Reticulum in Human Cells
Authors: Ma Dandan , Sun Wei , Nazmi Kamran , Veerman Enno C. I. , Bikker Floris J. , Jaspers Richard T. , Bolscher Jan G. M. , Wu Gang
Published: April 2020

Human salivary histatin 1 (Hst1) and Hst2 exhibit a series of cell-activating properties (e.g., promoting adhesion, spreading, migration and metabolic activity of mammalian cells). In contrast, Hst5 shows an anti-fungal property but no cell-activating properties. Previous findings suggest that their uptake and association with subcellular targets may play a determinant role in their functions. In this study, we studied the uptake dynamics and subcellular targets of Hst1, Hst2 and Hst5 in epithelial cells (HO1N1 human buccal carcinoma epithelial cell line). Confocal laser scanning microscopy (CLSM) revealed that fluorescently labeled Hst1 (F-Hst1) was taken up into the intracellular space of epithelial cells. Then, 60 min post-incubation, the total fluorescence of cell-associated F-Hst1, as measured using flow cytometry, was significantly higher compared to those of F-Hst2 and F-Hst5. In contrast, virtually no association occurred using the negative control—scrambled F-Hst1 (F-Hstscr). CLSM images revealed that F-Hst1, 2 and 5 co-localized with mitotrackerTM-labeled mitochondria. In addition, F-Hst1 and F-Hst2 but neither F-Hst5 nor F-Hst1scr co-localized with the ER-trackerTM-labeled endoplasmic reticulum. No co-localization of Hst1, 2 and 5 with lysosomes or the Golgi apparatus was observed. Furthermore, Hst1 and Hst2 but not Hst5 or Hst1scr significantly promoted the metabolic activity of both human epithelial cell lines, HaCaT human keratinocytes and primary human gingival fibroblasts.
TNFa and IL2 Encoding Oncolytic Adenovirus Activates Pathogen and Danger-Associated Immunological Signaling
Authors: Heiniö Camilla , Havunen Riikka , Santos Joao , de Lint Klaas , Cervera-Carrascon Victor , Kanerva Anna , Hemminki Akseli
Published: April 2020

In order to break tumor resistance towards traditional treatments, we investigate the response of tumor and immune cells to a novel, cytokine-armed oncolytic adenovirus: Ad5/3-d24-E2F-hTNFa-IRES-hIL2 (also known as TILT-123 and OAd.TNFa-IL2). There are several pattern recognition receptors (PRR) that might mediate adenovirus-infection recognition. However, the role and specific effects of each PRR on the tumor microenvironment and treatment outcome remain unclear. Hence, the aim of this study was to investigate the effects of OAd.TNFa-IL2 infection on PRR-mediated danger- and pathogen-associated molecular pattern (DAMP and PAMP, respectively) signaling. In addition, we wanted to see which PRRs mediate an antitumor response and are therefore relevant for optimizing this virotherapy. We determined that OAd.TNFa-IL2 induced DAMP and PAMP release and consequent tumor microenvironment modulation. We show that the AIM2 inflammasome is activated during OAd.TNFa-IL2 virotherapy, thus creating an immunostimulatory antitumor microenvironment.
A Regulatory Noncoding RNA, nc886, Suppresses Esophageal Cancer by Inhibiting the AKT Pathway and Cell Cycle Progression
Authors: Im Wonkyun Ronny , Lee Hyun-Sung , Lee Yeon-Su , Lee Ju-Seog , Jang Hee-Jin , Kim Seon-Young , Park Jong-Lyul , Lee Yeontaek , Kim Moon Soo , Lee Jong Mog , Kim In-Hoo , Jeon Sung Ho , Lee Yong Sun
Published: April 2020

nc886 is a regulatory non-coding RNA (ncRNA) whose expression is frequently silenced in malignancies. In the case of esophageal squamous cell carcinoma (ESCC), nc886 silencing is associated with shorter survival of patients, suggesting nc886’s tumor suppressor role in ESCC. However, this observation has not been complemented by an in-detail study about nc886’s impact on gene expression and cellular phenotypes. Here we have shown that nc886 inhibits AKT, a key protein in a renowned pro-survival pathway in cancer. nc886-silenced cells (nc886− cells) have activated AKT and altered expression of cell cycle genes. nc886− cells tend to have lower expression of CDKN2A and CDKN2C, both of which are inhibitors for cyclin-dependent kinase (CDK), and higher expression of CDK4 than nc886-expressing cells. As a result, nc886− cells are hyperactive in the progression of the G1 to S cell cycle phase, proliferate faster, and are more sensitive to palbociclib, which is a cancer therapeutic drug that targets CDK4/6. Experimentally by nc886 expression and knockdown, we have determined the AKT target genes and cell cycle genes that are controlled by nc886 (nc886-associated gene sets). These gene sets, in combination with pathologic staging and nc886 expression levels, are a vastly superior predictor for the survival of 108 ESCC patients. In summary, our study has elucidated in ESCC how nc886 inhibits cell proliferation to explain its tumor suppressor role and identified gene sets that are of future clinical utility, by predicting patient survival and responsiveness to a therapeutic drug.
Insulin Signaling in Intestinal Stem and Progenitor Cells as an Important Determinant of Physiological and Metabolic Traits in Drosophila
Authors: Strilbytska Olha M. , Semaniuk Uliana V. , Storey Kenneth B. , Yurkevych Ihor S. , Lushchak Oleh
Published: April 2020

The insulin–IGF-1 signaling (IIS) pathway is conserved throughout multicellular organisms and regulates many traits, including aging, reproduction, feeding, metabolism, stress resistance, and growth. Here, we present evidence of a survival-sustaining role for IIS in a subset of gut cells in Drosophila melanogaster, namely the intestinal stem cells (ISCs) and progenitor cells. Using RNAi to knockdown the insulin receptor, we found that inhibition of IIS in ISCs statistically shortened the lifespan of experimental flies compared with non-knockdown controls, and also shortened their survival under starvation or malnutrition conditions. These flies also showed decreased reproduction and feeding, and had lower amounts of glycogen and glucose in the body. In addition, increased expression was observed for the Drosophila transcripts for the insulin-like peptides dilp2, dilp5, and dilp6. This may reflect increased insulin signaling in peripheral tissues supported by up-regulation of the target of the brain insulin gene (tobi). In contrast, activation of IIS (via knockdown of the insulin pathway inhibitor PTEN) in intestinal stem and progenitor cells decreased fly resistance to malnutrition, potentially by affecting adipokinetic hormone signaling. Finally, Pten knockdown to enhance IIS also activated JAK–STAT signaling in gut tissue by up-regulation of upd2, upd3, and soc36 genes, as well as genes encoding the EGF receptor ligands spitz and vein. These results clearly demonstrate that manipulating insulin levels may be used to modulate various fly traits, which are important determinants of organismal survival.
Why Should Growth Hormone (GH) Be Considered a Promising Therapeutic Agent for Arteriogenesis? Insights from the GHAS Trial
Authors: Caicedo Diego , Devesa Pablo , Alvarez Clara V. , Devesa Jesús
Published: April 2020

Despite the important role that the growth hormone (GH)/IGF-I axis plays in vascular homeostasis, these kind of growth factors barely appear in articles addressing the neovascularization process. Currently, the vascular endothelium is considered as an authentic gland of internal secretion due to the wide variety of released factors and functions with local effects, including the paracrine/autocrine production of GH or IGF-I, for which the endothelium has specific receptors. In this comprehensive review, the evidence involving these proangiogenic hormones in arteriogenesis dealing with the arterial occlusion and making of them a potential therapy is described. All the elements that trigger the local and systemic production of GH/IGF-I, as well as their possible roles both in physiological and pathological conditions are analyzed. All of the evidence is combined with important data from the GHAS trial, in which GH or a placebo were administrated to patients suffering from critical limb ischemia with no option for revascularization. We postulate that GH, alone or in combination, should be considered as a promising therapeutic agent for helping in the approach of ischemic disease.
NeuroHeal Treatment Alleviates Neuropathic Pain and Enhances Sensory Axon Regeneration
Authors: Romeo-Guitart David , Casas Caty
Published: April 2020

Peripheral nerve injury (PNI) leads to the loss of motor, sensory, and autonomic functions, and often triggers neuropathic pain. During the last years, many efforts have focused on finding new therapies to increase axonal regeneration or to alleviate painful conditions. Still only a few of them have targeted both phenomena. Incipient or aberrant sensory axon regeneration is related to abnormal unpleasant sensations, such as hyperalgesia or allodynia. We recently have discovered NeuroHeal, a combination of two repurposed drugs; Acamprosate and Ribavirin. NeuroHeal is a neuroprotective agent that also enhances motor axon regeneration after PNI. In this work, we investigated its effect on sensory fiber regeneration and PNI-induced painful sensations in a rat model of spare nerve injury and nerve crush. The follow up of the animals showed that NeuroHeal treatment reduced the signs of neuropathic pain in both models. Besides, the treatment favored sensory axon regeneration, as observed in dorsal root ganglion explants. Mechanistically, the effects observed in vivo may improve the resolution of cell-protective autophagy. Additionally, NeuroHeal treatment modulated the P2X4-BDNF-KCC2 axis, which is an essential driver of neuropathic pain. These data open a new therapeutic avenue based on autophagic modulation to foster endogenous regenerative mechanisms and reduce the appearance of neuropathic pain in PNI.
Myelin Fat Facts: An Overview of Lipids and Fatty Acid Metabolism
Authors: Poitelon Yannick , Kopec Ashley M. , Belin Sophie
Published: April 2020

Myelin is critical for the proper function of the nervous system and one of the most complex cell–cell interactions of the body. Myelination allows for the rapid conduction of action potentials along axonal fibers and provides physical and trophic support to neurons. Myelin contains a high content of lipids, and the formation of the myelin sheath requires high levels of fatty acid and lipid synthesis, together with uptake of extracellular fatty acids. Recent studies have further advanced our understanding of the metabolism and functions of myelin fatty acids and lipids. In this review, we present an overview of the basic biology of myelin lipids and recent insights on the regulation of fatty acid metabolism and functions in myelinating cells. In addition, this review may serve to provide a foundation for future research characterizing the role of fatty acids and lipids in myelin biology and metabolic disorders affecting the central and peripheral nervous system.
Loss of Endothelial Glycocalyx Hyaluronan Impairs Endothelial Stability and Adaptive Vascular Remodeling after Arterial Ischemia
Authors: Wang Gangqi , de Vries Margreet R. , Sol Wendy M. P. J. , van Oeveren-Rietdijk Annemarie M. , de Boer Hetty C. , van Zonneveld Anton Jan , Quax Paul H. A. , Rabelink Ton J. , van den Berg Bernard M.
Published: April 2020

We recently reported that loss of hyaluronan (HA) from the endothelial glycocalyx leads to loss of vessel stability in specific microcirculatory vascular beds. Here we hypothesized that such derangements in the glycocalyx may also impair the adaptive response to vascular ischemia. Endothelial specific conditional hyaluronan synthase 2-KO (Has2-cKO) mice revealed reduced endothelial HA expression and lower hindlimb perfusion at baseline compared to control mice. After a single ligation of the common femoral artery in these mice, we observed dysregulated angiogenesis in the gastrocnemius muscle which did not restore capillary perfusion. Mechanistically, decreased endothelial binding of the pericyte-derived molecule angiopoietin1 (Ang1) could be observed in the Has2-cKO mouse. In vitro angiogenesis assays with an endothelial cell-pericyte coculture confirmed such disturbed Ang1-TIE2 signaling resulting in excessive angiogenesis upon loss of HA. These data could be of relevance to diabetes patients, where we confirm loss of endothelial HA in the microcirculation of muscle tissue, indicating that this may contribute to the known disturbed adaptation to ischemia in these patients. In summary, loss of endothelial HA results in impaired microvascular perfusion and endothelial stability in ischemic gastrocnemius muscle. Endothelial HA is a potential target to improve angiogenic therapy in diabetic patients with critical limb ischemia.
Combinatorial Therapies in Thyroid Cancer: An Overview of Preclinical and Clinical Progresses
Authors: Laetitia Gheysen , Sven Saussez , Fabrice Journe
Published: April 2020

Accounting for about 2% of cancers diagnosed worldwide, thyroid cancer has caused about 41,000 deaths in 2018. Despite significant progresses made in recent decades in the treatment of thyroid cancer, many resistances to current monotherapies are observed. In our complete review, we report all treatments that were tested in combination against thyroid cancer. Many preclinical studies investigating the effects of inhibitors of the MAPK and PI3K pathways highlighted the importance of mutations in such signaling pathways and their impacts on the subsequent efficacy of targeted therapies, thus reinforcing the need of more personalized therapeutic strategies. Our review also points out the multiple possibilities of combinatory strategies, particularly using therapies targeting proliferation, survival, angiogenesis, and in combination with conventional treatments such as chemotherapies. In any case, resistances to anticancer therapies always develop through the activation of alternative signaling pathways. Combinatory treatments aim to blockade such mechanisms, which are gradually decrypted, thus offering new perspectives for the future. The preclinical and clinical aspects of our review allow us to have a global opinion of the different therapeutic options currently evaluated in combination and to be aware about new perspectives of treatment of thyroid cancer.
Cholangiocarcinoma Disease Modelling Through Patients Derived Organoids
Authors: Amato Francesco , Rae Colin , Prete Maria Giuseppina , Braconi Chiara
Published: April 2020

Cancer organoids are 3D phenotypic cultures that can be established from resected or biopsy tumour samples and can be grown as mini tumours in the dish. Flourishing evidence supports the feasibility of patient derived organoids (PDO) from a number of solid tumours. Evidence for cholangiocarcinoma (CCA) PDO is still sparse but growing. CCA PDO lines have been established from resected early stage disease, advanced cancers and highly chemorefractory tumours. Cancer PDO was shown to recapitulate the 3D morphology, genomic landscape and transcriptomic profile of the source counterpart. They proved to be a valued model for drug discovery and sensitivity testing, and they showed to mimic the drug response observed in vivo in the patients. However, PDO lack representation of the intratumour heterogeneity and the tumour-stroma interaction. The efficiency rate of CCA PDO within the three different subtypes, intrahepatic, perihilar and distal, is still to be explored. In this manuscript we will review evidence for CCA PDO highlighting advantages and limitations of this novel disease model.
Sex-Specific Regulation of miR-29b in the Myocardium Under Pressure Overload is Associated with Differential Molecular, Structural and Functional Remodeling Patterns in Mice and Patients with Aortic Stenosis
Authors: García Raquel , Salido-Medina Ana B. , Gil Aritz , Merino David , Gómez Jenny , Villar Ana V. , González-Vílchez Francisco , Hurlé María A. , Nistal J. Francisco
Published: April 2020

Pressure overload in patients with aortic stenosis (AS) induces an adverse remodeling of the left ventricle (LV) in a sex-specific manner. We assessed whether a sex-specific miR-29b dysregulation underlies this sex-biased remodeling pattern, as has been described in liver fibrosis. We studied mice with transverse aortic constriction (TAC) and patients with AS. miR-29b was determined in the LV (mice, patients) and plasma (patients). Expression of remodeling-related markers and histological fibrosis were determined in mouse LV. Echocardiographic morpho-functional parameters were evaluated at baseline and post-TAC in mice, and preoperatively and 1 year after aortic valve replacement (AVR) in patients with AS. In mice, miR-29b LV regulation was opposite in TAC-males (down-regulation) and TAC-females (up-regulation). The subsequent changes in miR-29b targets (collagens and GSK-3β) revealed a remodeling pattern that was more fibrotic in males but more hypertrophic in females. Both systolic and diastolic cardiac functions deteriorated more in TAC-females, thus suggesting a detrimental role of miR-29b in females, but was protective in the LV under pressure overload in males. Clinically, miR-29b in controls and patients with AS reproduced most of the sexually dimorphic features observed in mice. In women with AS, the preoperative plasma expression of miR-29b paralleled the severity of hypertrophy and was a significant negative predictor of reverse remodeling after AVR; therefore, it may have potential value as a prognostic biomarker.
Characterization of Sialic Acid-Binding Immunoglobulin-Type Lectins in Fish Reveals Teleost-Specific Structures and Expression Patterns
Authors: Bornhöfft Kim F. , Martorell Ribera Joan , Viergutz Torsten , Venuto Marzia T. , Gimsa Ulrike , Galuska Sebastian P. , Rebl Alexander
Published: April 2020

The cellular glycocalyx of vertebrates is frequently decorated with sialic acid residues. These sialylated structures are recognized by sialic acid-binding immunoglobulin-type lectins (Siglecs) of immune cells, which modulate their responsiveness. Fifteen Siglecs are known to be expressed in humans, but only four Siglecs are regularly present in fish: Siglec1, CD22, myelin-associated glycoprotein (MAG), and Siglec15. While several studies have dealt with the physiological roles of these four Siglecs in mammals, little is known about Siglecs in fish. In the present manuscript, the expression landscapes of these Siglecs were determined in the two salmonid species Oncorhynchus mykiss and Coregonus maraena and in the percid fish Sander lucioperca. This gene-expression profiling revealed that the expression of MAG is not restricted to neuronal cells but is detectable in all analyzed blood cells, including erythrocytes. The teleostean MAG contains the inhibitory motif ITIM; therefore, an additional immunomodulatory function of MAG is likely to be present in fish. Besides MAG, Siglec1, CD22, and Siglec15 were also expressed in all analyzed blood cell populations. Interestingly, the expression profiles of genes encoding Siglecs and particular associated enzymes changed in a gene- and tissue-specific manner when Coregonus maraena was exposed to handling stress. Thus, the obtained data indicate once more that stress directly affects immune-associated processes.
The Transcription Factor OVOL2 Represses ID2 and Drives Differentiation of Trophoblast Stem Cells and Placental Development in Mice
Authors: Jeyarajah Mariyan J. , Jaju Bhattad Gargi , Hillier Dendra M. , Renaud Stephen J.
Published: April 2020

Trophoblasts are the first cell type to be specified during embryogenesis, and they are essential for placental morphogenesis and function. Trophoblast stem (TS) cells are the progenitor cells for all trophoblast lineages; control of TS cell differentiation into distinct trophoblast subtypes is not well understood. Mice lacking the transcription factor OVO-like 2 (OVOL2) fail to produce a functioning placenta, and die around embryonic day 10.5, suggesting that OVOL2 may be critical for trophoblast development. Therefore, our objective was to determine the role of OVOL2 in mouse TS cell fate. We found that OVOL2 was highly expressed in mouse placenta and differentiating TS cells. Placentas and TS cells lacking OVOL2 showed poor trophoblast differentiation potential, including increased expression of stem-state associated genes (Eomes, Esrrb, Id2) and decreased levels of differentiation-associated transcripts (Gcm1, Tpbpa, Prl3b1, Syna). Ectopic OVOL2 expression in TS cells elicited precocious differentiation. OVOL2 bound proximate to the gene encoding inhibitor of differentiation 2 (ID2), a dominant negative helix-loop-helix protein, and directly repressed its activity. Overexpression of ID2 was sufficient to reinforce the TS cell stem state. Our findings reveal a critical role of OVOL2 as a regulator of TS cell differentiation and placental development, in-part by coordinating repression of ID2.
The Impact of Immunomodulatory Treatment on Kappa Free Light Chains as Biomarker in Neuroinflammation
Authors: Konen Franz Felix , Wurster Ulrich , Witte Torsten , Jendretzky Konstantin Fritz , Gingele Stefan , Tumani Hayrettin , Sühs Kurt-Wolfram , Stangel Martin , Schwenkenbecher Philipp , Skripuletz Thomas
Published: April 2020

Background: Kappa free light chains (KFLC) are a promising new biomarker to detect neuroinflammation. Still, the impact of pre-analytical effects on KFLC concentrations was not investigated. Methods: KFLC concentrations were measured in serum and cerebrospinal fluid (CSF) of patients with a newly diagnosed multiple sclerosis (MS) or clinically isolated syndrome (CIS) before (n = 42) or after therapy with high-dose methylprednisolone (n = 65). In prospective experiments, KFLC concentrations were analyzed in the same patients in serum before and after treatment with high-dose methylprednisolone (n = 16), plasma exchange (n = 12), immunoadsorption (n = 10), or intravenous immunoglobulins (n = 10). In addition, the influence of storage time, sample method, and contamination of CSF with blood were investigated. Results: Patients diagnosed with MS/CIS and treated with methylprednisolone showed significantly lower KFLC concentrations in serum as untreated patients. Repeated longitudinal investigations revealed that serum KFLC concentrations continuously decreased after each application of methylprednisolone. In contrast, other immune therapies and further pre-analytical conditions did not influence KFLC concentrations. Conclusion: Our results show prominent effects of steroids on KFLC concentrations. In contrast, various other pre-analytical conditions did not influence KFLC concentrations, indicating the stability of this biomarker.
The Cuprizone Model: Dos and Do Nots
Authors: Zhan Jiangshan , Mann Teresa , Joost Sarah , Behrangi Newshan , Frank Marcus , Kipp Markus
Published: April 2020

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. Various pre-clinical models with different specific features of the disease are available to study MS pathogenesis and to develop new therapeutic options. During the last decade, the model of toxic demyelination induced by cuprizone has become more and more popular, and it has contributed substantially to our understanding of distinct yet important aspects of the MS pathology. Here, we aim to provide a practical guide on how to use the cuprizone model and which pitfalls should be avoided.
Superhydrophobic Coatings Based on Siloxane Resin and Calcium Hydroxide Nanoparticles for Marble Protection
Authors: Chatzigrigoriou Aikaterini , Karapanagiotis Ioannis , Poulios Ioannis
Published: April 2020

Calcium hydroxide (Ca(OH2)) nanoparticles are produced following an easy, ion exchange process. The produced nanoparticles are characterized using transmission electron microscopy (TEM) and Fourier- transform infrared spectroscopy (FTIR) and are then dispersed in an aqueous emulsion of silanes/siloxanes. The dispersions are sprayed on marble and the surface structures of the deposited coatings are revealed using scanning electron microscopy (SEM). By adjusting the nanoparticle concentration, the coated marble obtains superhydrophobic and water repellent properties, as evidenced by the high static contact angles of water drops (> 150°) and the low sliding angles (< 10°). Because Ca(OH)2 is chemically compatible with limestone-like rocks, which are the most common stones found in buildings and objects of the cultural heritage, the produced composite coatings have the potential to be used for conservation purposes. For comparison, the wetting properties of another superhydrophobic and water repellent coating composed of the same siloxane material and silica (SiO2) nanoparticles, which were commonly used in several previously published reports, were investigated. The suggested siloxane+Ca(OH)2 composite coating offers good protection against water penetration by capillarity and has a small effect on the aesthetic appearance of marble, according to colorimetric measurements.
Ambient-Processed, Additive-Assisted CsPbBr3 Perovskite Light-Emitting Diodes with Colloidal NiOx Nanoparticles for Efficient Hole Transporting
Authors: Huang Chun-Yuan , Chang Sheng-Po , Ansay Arjun G. , Wang Zi-Hao , Yang Chih-Chiang
Published: April 2020

In this study, the electrically driven perovskite light-emitting diodes (PeLEDs) were investigated by hybridizing the organic polyethylene oxide, 1,3,5-tris (N-phenylbenzimiazole-2-yl) benzene (TPBi), and bis(3,5-difluoro-2-(2-pyridyl)phenyl-(2-carboxypyridyl) iridium III (FIrpic) with CsPbBr3 in the emission layer and adopting the colloidal NiOx nanoparticle (NP) hole transport layer. The synthesized NiOx NPs, having an average size of ~5 nm, can be spin-coated to become a smooth and close-packed film on the indium–tin–oxide anode. The NiOx NP layer possesses an overall transmittance of ~80% at 520 nm, which is about the peak position of electroluminescence (EL) spectra of CsPbBr3 emission layer. The coating procedures of NiOx NP and CsPbBr3 layers were carried out in ambient air. The novel PeLED turned on at 2.4 V and emitted bright EL of 4456 cd/m2 at 7 V, indicating the remarkable nonradiative-related defect elimination by organic additive addition and significant charge balance achieved by the NiOx NP layer.
Zinc/Silver Particle (Zn/AgP) Composite Coatings: Evaluation of Corrosion in Physiological Environments and Antibacterial Activity against P. aeruginosa
Authors: Castro-Rodríguez Berenice , Terán-López Arnulfo , Reyes-Vidal Yolanda , Bácame-Valenzuela Francisco J. , Flores José G. , Ortega Raúl , Mojica José , Acosta-Smith Erika , Vázquez-Arenas Jorge , Lara René H. , Trejo Gabriel
Published: April 2020

In this work, zinc/silver particle (Zn/AgP) composite coatings were manufactured by electrodeposition to investigate their antibacterial capacity and corrosion rate in physiological environments. The morphology and composition of the coatings were analysed by glow-discharge optical emission spectroscopy and scanning electron microscopy coupled to an energy dispersive spectrometer. The results showed the formation of Zn/AgP composite coatings with a homogeneous distribution of Ag throughout the coating surface and depth. Additionally, the Ag content in the coatings increased with increasing concentrations of AgP in the electrolytic solution. The Zn/AgP composite coatings with 0.30 wt.% Ag on the surface (0.30 wt.% Agsurf) showed efficiencies close to 100% growth inhibition of the bacteria Pseudomonas aeruginosa after 10 min of contact. The corrosion rate of the Zn and the Zn/AgP (0.30 wt.% Agsurf) coatings in Hank’s, Ringer’s and Phosphate buffered saline (PBS) solutions was evaluated by polarization curves and by immersion tests over different time periods (7, 30, and 40 days). The corrosion rate of the Zn/AgP (0.30 wt.% Agsurf) coatings was on the order of tenths of microns per year and the amount of zinc mass dissolving per day was in the range of 0.15 to 0.7 mg cm−2. Additionally, the surface of the coatings was analysed by X-ray diffraction (XRD) after 40 days of immersion. These results showed the formation of ZnO, as the main corrosion product, in the samples immersed in Hank’s and Ringer’s solutions. In the samples immersed in PBS, the formation of a passivating film of Zn2(PO4)3·2H2O was detected.
Environmentally Friendly Water-Based Self-Crosslinking Acrylate Dispersion Containing Magnesium Nanoparticles and Their Films Exhibiting Antimicrobial Properties
Authors: Steinerová Denisa , Kalendová Andréa , Machotová Jana , Pejchalová Marcela
Published: April 2020

A water-based polymeric acrylate dispersion (latex) containing MgO nanoparticles, which had been added at a concentration of 1.5% (with respect to the monomers) during the preparation procedure, was investigated as an environmentally friendly binder for sanitary interior paints. The properties of this new latex were compared to those of a reference system free of the magnesium nanoparticles, synthesized by the same route, i.e., by semi-continuous emulsion polymerization. Tests were made in order to ascertain the mechanical and chemical properties, flash corrosion resistance and antimicrobial effect of the latex films. The results revealed that the new latex containing magnesium nanoparticles provided solvent-resistant coating films having pronounced antimicrobial activity against all the tested bacterial and fungal strains. The desirable antimicrobial properties can be ascribed to the sharp-edged character of magnesium nanoparticles, the peroxidation of lipids and the formation of reactive oxygen species. Moreover, no flash corrosion was formed beneath coating films containing magnesium nanoparticles, which can be attributed to the alkaline action due to the dissolution of a fraction of MgO in latex medium. The results of all of the tests provided evidence of the superiority of the polymeric dispersion with the magnesium nanoparticles to the reference system containing no nanoparticles.
Fabrication of Large Area Ag Gas Diffusion Electrode via Electrodeposition for Electrochemical CO2 Reduction
Authors: Oh Seonhwa , Park Hyanjoo , Kim Hoyoung , Park Young Sang , Ha Min Gwan , Jang Jong Hyun , Kim Soo-Kil
Published: April 2020

For the improvement for the commercialization of electrochemical carbon dioxide (CO2) conversion technology, it is important to develop a large area Ag gas diffusion electrode (GDE), that exhibits a high electrochemical CO2 conversion efficiency and high cell performance in a membrane electrode assembly (MEA)-type CO2 electrolyzer. In this study, the electrodeposition of Ag on a carbon-paper gas diffusion layer was performed to fabricate a large area (25.5 and 136 cm2) Ag GDE for application to an MEA-type CO2 electrolyzer. To achieve uniformity throughout this large area, an optimization of the electrodeposition variables, such as the electrodes system, electrodes arrangement, deposition current and deposition time was performed with respect to the total electrolysis current, CO production current, Faradaic efficiency (FE), and deposition morphology. The optimal conditions, that is, galvanostatic deposition at 0.83 mA/cm2 for 50 min in a horizontal, two-electrode system with a working-counter electrode distance of 4 cm, did ensure a uniform performance throughout the electrode. The position-averaged CO current densities of 2.72 and 2.76 mA/cm2 and FEs of 83.78% (with a variation of 3.25%) and 82.78% (with a variation of 8.68%) were obtained for 25.5 and 136 cm2 Ag GDEs, respectively. The fabricated 136 cm2 Ag GDE was further used in MEA-type CO2 electrolyzers having an active geometric area of 107.44 cm2, giving potential-dependent CO conversion efficiencies of 41.99%–57.75% at Vcell = 2.2–2.6 V.
Stakeholders’ Perspectives for the Development of a Point-of-Care Diagnostics Curriculum in Rural Primary Clinics in South Africa—Nominal Group Technique
Authors: Chamane Nkosinothando , Kuupiel Desmond , Mashamba-Thompson Tivani Phosa
Published: April 2020

Poor knowledge and adherence to point-of-care (POC) HIV testing standards have been reported in rural KwaZulu-Natal (KZN), a high HIV prevalent setting. Improving compliance to HIV testing standards is critical, particularly during the gradual phasing out of lay counsellor providers and the shifting of HIV testing and counselling duties to professional nurses. The main objective of this study was to identify priority areas for development of POC diagnostics curriculum to improve competence and adherence to POC diagnostics quality standards for primary healthcare (PHC) nurses in rural South Africa. Method: PHC clinic stakeholders were invited to participate in a co-creation workshop. Participants were purposely sampled from each of the 11 KwaZulu-Natal Districts. Through the Nominal Group Technique (NGT), participants identified training related challenges concerning delivery of quality point of care diagnostics and ranked them from highest to lowest priority. An importance ranking score (scale 1–5) was calculated for each of the identified challenges. Results: Study participants included three PHC professional nurses, one TB professional nurse, one HIV lay councilor, one TB assistant and three POC diagnostics researchers, aged 23–50. Participants identified ten POC diagnostics related challenges. Amongst the highest ranked challenges were the following:absence of POC testing Curriculum for nurses, absence of training of staff on HIV testing and counselling as lay counsellor providers are gradually being phased out,. absence of Continuous Professional Development opportunities and lack of Staff involvement in POC Management programs. Conclusion: Key stakeholders perceived training of PHC nurses as the highest priority for the delivery of quality POC diagnostic testing at PHC level. We recommend continual collaboration among all POC diagnostics stakeholders in the development of an accessible curriculum to improve providers’ competence and ensure sustainable quality delivery of POC diagnostic services in rural PHC clinics.
Automatic Annotation of Narrative Radiology Reports
Authors: Krsnik Ivan , Glavaš Goran , Krsnik Marina , Miletić Damir , Štajduhar Ivan
Published: April 2020

Narrative texts in electronic health records can be efficiently utilized for building decision support systems in the clinic, only if they are correctly interpreted automatically in accordance with a specified standard. This paper tackles the problem of developing an automated method of labeling free-form radiology reports, as a precursor for building query-capable report databases in hospitals. The analyzed dataset consists of 1295 radiology reports concerning the condition of a knee, retrospectively gathered at the Clinical Hospital Centre Rijeka, Croatia. Reports were manually labeled with one or more labels from a set of 10 most commonly occurring clinical conditions. After primary preprocessing of the texts, two sets of text classification methods were compared: (1) traditional classification models—Naive Bayes (NB), Logistic Regression (LR), Support Vector Machine (SVM), and Random Forests (RF)—coupled with Bag-of-Words (BoW) features (i.e., symbolic text representation) and (2) Convolutional Neural Network (CNN) coupled with dense word vectors (i.e., word embeddings as a semantic text representation) as input features. We resorted to nested 10-fold cross-validation to evaluate the performance of competing methods using accuracy, precision, recall, and F 1 score. The CNN with semantic word representations as input yielded the overall best performance, having a micro-averaged F 1 score of 86.7 % . The CNN classifier yielded particularly encouraging results for the most represented conditions: degenerative disease ( 95.9 % ), arthrosis ( 93.3 % ), and injury ( 89.2 % ). As a data-hungry deep learning model, the CNN, however, performed notably worse than the competing models on underrepresented classes with fewer training instances such as multicausal disease or metabolic disease. LR, RF, and SVM performed comparably well, with the obtained micro-averaged F 1 scores of 84.6 % , 82.2 % , and 82.1 % , respectively.
Increased Circulating Levels of Tissue-Type Plasminogen Activator Are Associated with the Risk of Spontaneous Abortion During the First Trimester of Pregnancy
Authors: Monteiro Lara J. , Varas-Godoy Manuel , Acuña-Gallardo Stephanie , Correa Paula , Passalacqua Gianluca , Monckeberg Max , Rice Gregory E. , Illanes Sebastián E.
Published: April 2020

Spontaneous abortion is a common complication in early pregnancy, with an incidence of around 20%. Ultrasound scan and measurement of human chorionic gonadotropin are used to identify patients at risk of spontaneous abortion; however, there is a clinical need to find new biomarkers to prospectively identify patients before the onset of clinical symptoms. Here, we aim to investigate potential biomarkers of spontaneous abortion taken in the first clinical appointment of pregnancy. A case–control study was conducted based on a prospectively collected cohort in which cases and controls were retrospectively stratified based on pregnancy outcome: normal healthy pregnancies (controls = 33) and pregnancies that ended in spontaneous abortion (cases = 10). We evaluated extracellular vesicles isolated by precipitation with ExoQuick™ and protein concentrations of tissue plasminogen activator, leptin, and adiponectin measured by ELISA. The extracellular vesicles showed the typical morphology and membrane proteins: CD63, Alix, and Flotilin-1. The size distributions of the isolated extracellular vesicles were 112 ± 27 and 118 ± 28 nm in diameter for controls and spontaneous abortion, respectively, and the total amount of extracellular vesicles did not show any difference between controls and the spontaneous abortion group. The tissue plasminogen activator showed a significant difference (p = 0.0004) between both groups, although neither adiponectin nor leptin revealed significant changes, indicating that women who had spontaneous abortions have significantly higher levels of tissue plasminogen activator than women who had normal pregnancies.
Semi-Supervised FaceGAN for Face-Age Progression and Regression with Synthesized Paired Images
Authors: Pham Quang T. M. , Yang Janghoon , Shin Jitae
Published: April 2020

The performance of existing face age progression or regression methods is often limited by the lack of sufficient data to train the model. To deal with this problem, we introduce a novel framework that exploits synthesized images to improve the performance. A conditional generative adversarial network (GAN) is first developed to generate facial images with targeted ages. The semi-supervised GAN, called SS-FaceGAN, is proposed. This approach considers synthesized images with a target age and the face images from the real data so that age and identity features can be explicitly utilized in the objective function of the network. We analyze the performance of our method over previous studies qualitatively and quantitatively. The experimental results show that the SS-FaceGAN model can produce realistic human faces in terms of both identity preservation and age preservation with the quantitative results of a decent face detection rate of 97% and similarity score of 0.30 on average.
Causes of Decline in the Korean Fir Based on Spatial Distribution in the Mt. Halla Region in Korea: A Meta-Analysis
Authors: Ahn Ung San , Yun Young Seok
Published: April 2020

Research Highlights: Technology advances have allowed for a new approach to research the decline of the Korean fir (Abies koreana E.H.Wilson). This study provides insights into the exact causes leading to this decline. Background and Objectives: Various factors could lead to the decline of fir trees around Mt. Halla, Korea, but these have not yet been verified. Here, the Korean fir across Mt. Halla were classified as dead or living and mapped using high-resolution orthorectified aerial images and three-dimensional (3D) stereoplotting. Materials and Methods: Aerial photographs were used to map spatial distribution and analyze the distribution patterns and mortality of the Korean fir. The electronic stereoplotting program (Geo3Di-PRO) enabled the creation of 3D images from aerial photographs. General, altitudinal, and topographical distribution was assessed. Results: Their accumulated percent mortality rate (APMR) showed positive correlations with altitude and tree density, a negative correlation with terrain slope, and no consistent correlation with solar radiation. The results indicate that increases in the density of Korean firs are related to decreased growth in areas at high altitude, on gentle slopes, and with high solar radiation. Consistent positive correlations between density and APMR indicate that fir mortality can be attributed to environmental deterioration and the establishment of unfavorable growth conditions. Areas with high APMR and density had gentle slopes, thus high soil moisture, or relatively high annual precipitation owing to high altitude. Conclusion: Fir mortality on Mt. Halla can be attributed to long-term persistently high rainfall and subsequent excess soil moisture.
Retrieval of Forest Structural Parameters from Terrestrial Laser Scanning: A Romanian Case Study
Authors: Pascu Ionuț-Silviu , Dobre Alexandru-Claudiu , Badea Ovidiu , Tanase Mihai Andrei
Published: April 2020

Research Highlights: The present study case investigates the differences occurring when tree’s biophysical parameters are extracted through single and multiple scans. Scan sessions covered mountainous and hill regions of the Carpathian forests. Background and Objectives: We focused on analyzing stems, as a function of diameter at breast height (DBH) and the total height (H), at sample plot level for natural forests, with the purpose of assessing the potential for transitioning available methodology to field work in Romania. Materials and Methods: We performed single and multiple scans using a FARO Focus 3D X130 phase shift terrestrial laser scanner at 122 kpts and 0.3:0.15 mm noise compression ratio, resulting in an average point density of 6pts at 10m. The point cloud we obtained underpinned the DBH and heights analysis. In order to reach values similar to those measured in the field, we used both the original and the segmented point clouds, postprocessed in subsamples of different radii. Results: Pearson’s correlation coefficient above 0.8 for diameters showed high correlation with the field measurements. Diameter averages displayed differences within tolerances (0.02 m) for 10 out of 12 plots. Height analysis led to poorer results. For both acquisition methods, the values of the correlation coefficient peaked at 0.6. The initial hypothesis that trees positioned at a distance equivalent to their height can be measured more precise, was not valid; no increase in correlation strength was visible for either heights or diameters as the distance from scanner varied (r = 0.52). Conclusions: With regard to tree biophysical parameters extraction, the acquisition method has no major influence upon visible trees. We emphasize the term “visible”, as an increase in the number of acquisitions led to an increased number of detected trees (16% in old stands and 29% in young stands).