bluuebunny/crossref_metadata_2025 huggingface dataset:
Random Forest Classification of Alcohol Use Disorder Using EEG Source Functional Connectivity, Neuropsychological Functioning, and Impulsivity Measures
Authors: Kamarajan Chella , Ardekani Babak A. , Pandey Ashwini K. , Chorlian David B. , Kinreich Sivan , Pandey Gayathri , Meyers Jacquelyn L. , Zhang Jian , Kuang Weipeng , Stimus Arthur T. , Porjesz Bernice
Published: March 2020

Individuals with alcohol use disorder (AUD) manifest a variety of impairments that can be attributed to alterations in specific brain networks. The current study aims to identify features of EEG-based functional connectivity, neuropsychological performance, and impulsivity that can classify individuals with AUD (N = 30) from unaffected controls (CTL, N = 30) using random forest classification. The features included were: (i) EEG source functional connectivity (FC) of the default mode network (DMN) derived using eLORETA algorithm, (ii) neuropsychological scores from the Tower of London test (TOLT) and the visual span test (VST), and (iii) impulsivity factors from the Barratt impulsiveness scale (BIS). The random forest model achieved a classification accuracy of 80% and identified 29 FC connections (among 66 connections per frequency band), 3 neuropsychological variables from VST (total number of correctly performed trials in forward and backward sequences and average time for correct trials in forward sequence) and all four impulsivity scores (motor, non-planning, attentional, and total) as significantly contributing to classifying individuals as either AUD or CTL. Although there was a significant age difference between the groups, most of the top variables that contributed to the classification were not significantly correlated with age. The AUD group showed a predominant pattern of hyperconnectivity among 25 of 29 significant connections, indicating aberrant network functioning during resting state suggestive of neural hyperexcitability and impulsivity. Further, parahippocampal hyperconnectivity with other DMN regions was identified as a major hub region dysregulated in AUD (13 connections overall), possibly due to neural damage from chronic drinking, which may give rise to cognitive impairments, including memory deficits and blackouts. Furthermore, hypoconnectivity observed in four connections (prefrontal nodes connecting posterior right-hemispheric regions) may indicate a weaker or fractured prefrontal connectivity with other regions, which may be related to impaired higher cognitive functions. The AUD group also showed poorer memory performance on the VST task and increased impulsivity in all factors compared to controls. Features from all three domains had significant associations with one another. These results indicate that dysregulated neural connectivity across the DMN regions, especially relating to hyperconnected parahippocampal hub as well as hypoconnected prefrontal hub, may potentially represent neurophysiological biomarkers of AUD, while poor visual memory performance and heightened impulsivity may serve as cognitive-behavioral indices of AUD.
Multi-Objective Optimizing Curvilinear Steel Bar Structures of Hyperbolic Paraboloid Canopy Roofs
Authors: Dzwierzynska Jolanta
Published: March 2020

The paper concerns shaping curvilinear steel bar structures that are hyperbolic paraboloid canopy roofs by means of parametric design software Rhinoceros/Grasshopper and Karamba 3D. Hyperbolic paraboloid shape has found applications in various solutions of building roofs, mainly as reinforced concrete or steel coverings made of bent sheets. The hyperbolic paraboloid as a ruled surface can be a good base surface for forming bar grids. However, there are few studies on the effect of its division and the obtained topology of bar structures on their load-bearing capacity. In order to fill this gap, the aim of the presented research was to compare the effectiveness of various curvilinear steel bar structures of hyperbolic paraboloid canopy roofs covering the same plane, as well as defining both the most effective pattern of their structural grids and the optimal supporting system. This analysis was carried out thanks to the application of genetic algorithms enabling the free flow of information between geometrical and structural models, as well as thanks to the obtained result of multi-objective optimizations of the shaped structures for given boundary conditions. Minimal mass of the structure as well as minimal deflection of the structural members were assumed as the optimization criteria.
Autophagic Inhibition via Lysosomal Integrity Dysfunction Leads to Antitumor Activity in Glioma Treatment
Authors: Hwang Hui-Yun , Cho Yoon Sun , Kim Jin Young , Yun Ki Na , Yoo Jong Shin , Lee Eunhyeong , Kim Injune , Kwon Ho Jeong
Published: March 2020

Manipulating autophagy is a promising strategy for treating cancer as several autophagy inhibitors are shown to induce autophagic cell death. One of these, autophagonizer (APZ), induces apoptosis-independent cell death by binding an unknown target via an unknown mechanism. To identify APZ targets, we used a label-free drug affinity responsive target stability (DARTS) approach with a liquid chromatography/tandem mass spectrometry (LC–MS/MS) readout. Of 35 protein interactors, we identified Hsp70 as a key target protein of unmodified APZ in autophagy. Either APZ treatment or Hsp70 inhibition attenuates integrity of lysosomes, which leads to autophagic cell death exhibiting an excellent synergism with a clinical drug, temozolomide, in vitro, in vivo, and orthotropic glioma xenograft model. These findings demonstrate the potential of APZ to induce autophagic cell death and its development to combinational chemotherapeutic agent for glioma treatment. Collectively, our study demonstrated that APZ, a new autophagy inhibitor, can be used as a potent antitumor drug candidate to get over unassailable glioma and revealed a novel function of Hsp70 in lysosomal integrity regulation of autophagy.
Precision Medicine Tumor Boards: Clinical Applicability of Personalized Treatment Concepts in Ovarian Cancer
Authors: Aust Stefanie , Schwameis Richard , Gagic Tamara , Müllauer Leonhard , Langthaler Eva , Prager Gerald , Grech Christina , Reinthaller Alexander , Krainer Michael , Pils Dietmar , Grimm Christoph , Polterauer Stephan
Published: March 2020

Background: Treating cancer according to its molecular alterations (i.e., targeted treatment, TT) is the goal of precision medicine tumor boards (PTBs). Their clinical applicability has been evaluated for ovarian cancer patients in this analysis. Methods: All consecutive ovarian cancer patients discussed in a PTB at the Medical University of Vienna, Austria, from April 2015 to April 2019 were included (n = 44). Results: In 38/44 (86%) cases, at least one mutation, deletion or amplification was detected. The most frequently altered genes were p53 (64%), PI3K pathway (18%), KRAS (14%), BRCA1 (11%) and BRCA2 (2%). In 31 patients (70%) a TT was recommended. A total of 12/31 patients (39%) received the recommended therapy. Median time from indication for PTB to TT start was 65 days (15–216). Median time to treatment failure was 2.7 months (0.2–13.2). Clinical benefit rate (CBR) was 42%. Reasons for treatment discontinuation were disease progression (42%), poor performance status (PS > 2; 25%), death (17%) or treatment related side effects (8%). In 61% the TT was not administered—mainly due to PS > 2. Conclusion: Even though a TT recommendation can be derived frequently, clinical applicability remains limited due to poor patients’ general condition after exploitation of standard treatment. However, we observed antitumor activity in a substantial number of heavily pretreated patients.
The Clinicopathological Features and Genetic Mutations in Gastric Cancer Patients According to EMAST and MSI Status
Authors: Fang Wen-Liang , Chen Ming-Huang , Huang Kuo-Hung , Chang Shih-Ching , Lin Chien-Hsing , Chao Yee , Lo Su-Shun , Li Anna Fen-Yau , Wu Chew-Wun , Shyr Yi-Ming
Published: March 2020

Background: There has been no report regarding the clinicopathological features and genetic mutations regarding elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) in gastric cancer (GC). Methods: The correlation among EMAST status, microsatellite instability (MSI) status, mutations of common GC-related genes and 16 DNA repair-associated genes, and the clinicopathological features were analyzed. Results: Among the 360 GC patients enrolled, there were 76 (21.1%) with EMAST+ tumors and 284 with EMAST− tumors, and 59 (16.4%) were MSI-high (MSI-H) tumors, and 301 were microsatellite stable (MSS) tumors. Patients with EMAST+ tumors exhibited an earlier pathological T category and had more genetic mutations in the PI3K/AKT pathway, ARID1A and DNA repair-associated genes than those with EMAST− tumors. Patients with MSI-H tumors have more genetic mutations in the PI3K/AKT pathway and DNA repair-associated genes than those with MSS tumors. In the subgroup analysis for MSI-H GC, EMAST+ tumors were associated with earlier pathological T and N categories, earlier TNM stages, higher frequency of DNA-repair-associated genetic mutations, and a better survival rate than EMAST− tumors. Conclusions: PI3K/AKT pathway mutations may play an important role in EMAST+ and/or MSI-H GC. EMAST+/MSI-H tumors seem to represent a different subtype of gastric cancer from EMAST−/MSI-H tumors.
The Role of Carcinogenesis-Related Biomarkers in the Wnt Pathway and Their Effects on Epithelial–Mesenchymal Transition (EMT) in Oral Squamous Cell Carcinoma
Authors: Bai Yunpeng , Sha Jingjing , Kanno Takahiro
Published: March 2020

As oral squamous cell carcinoma (OSCC) can develop from potentially malignant disorders (PMDs), it is critical to develop methods for early detection to improve the prognosis of patients. Epithelial–mesenchymal transition (EMT) plays an important role during tumor progression and metastasis. The Wnt signaling pathway is an intercellular pathway in animals that also plays a fundamental role in cell proliferation and regeneration, and in the function of many cell or tissue types. Specific components of master regulators such as epithelial cadherin (E-cadherin), Vimentin, adenomatous polyposis coli (APC), Snail, and neural cadherin (N-cadherin), which are known to control the EMT process, have also been implicated in the Wnt cascade. Here, we review recent findings on the Wnt signaling pathway and the expression mechanism. These regulators are known to play roles in EMT and tumor progression, especially in OSCC. Characterizing the mechanisms through which both EMT and the Wnt pathway play a role in these cellular pathways could increase our understanding of the tumor genesis process and may allow for the development of improved therapeutics for OSCC.
Detection of Glioblastoma Subclinical Recurrence Using Serial Diffusion Tensor Imaging
Authors: Jin Yan , Randall James W. , Elhalawani Hesham , Al Feghali Karine A. , Elliott Andrew M. , Anderson Brian M. , Lacerda Lara , Tran Benjamin L. , Mohamed Abdallah S. , Brock Kristy K. , Fuller Clifton D. , Chung Caroline
Published: March 2020

Glioblastoma is an aggressive brain tumor with a propensity for intracranial recurrence. We hypothesized that tumors can be visualized with diffusion tensor imaging (DTI) before they are detected on anatomical magnetic resonance (MR) images. We retrospectively analyzed serial MR images from 30 patients, including the DTI and T1-weighted images at recurrence, at 2 months and 4 months before recurrence, and at 1 month after radiation therapy. The diffusion maps and T1 images were deformably registered longitudinally. The recurrent tumor was manually segmented on the T1-weighted image and then applied to the diffusion maps at each time point to collect mean FA, diffusivities, and neurite density index (NDI) values, respectively. Group analysis of variance showed significant changes in FA (p = 0.01) and NDI (p = 0.0015) over time. Pairwise t tests also revealed that FA and NDI at 2 months before recurrence were 11.2% and 6.4% lower than those at 1 month after radiation therapy (p < 0.05), respectively. Changes in FA and NDI were observed 2 months before recurrence, suggesting that progressive microstructural changes and neurite density loss may be detectable before tumor detection in anatomical MR images. FA and NDI may serve as non-contrast MR-based biomarkers for detecting subclinical tumors.
Diversity of Clinically Relevant Outcomes Resulting from Hypofractionated Radiation in Human Glioma Stem Cells Mirrors Distinct Patterns of Transcriptomic Changes
Authors: Kalasauskas Darius , Sorokin Maxim , Sprang Bettina , Elmasri Alhassan , Viehweg Sina , Salinas Gabriela , Opitz Lennart , Rave-Fraenk Margret , Schulz-Schaeffer Walter , Kantelhardt Sven Reiner , Giese Alf , Buzdin Anton , Kim Ella L.
Published: March 2020

Hypofractionated radiotherapy is the mainstay of the current treatment for glioblastoma. However, the efficacy of radiotherapy is hindered by the high degree of radioresistance associated with glioma stem cells comprising a heterogeneous compartment of cell lineages differing in their phenotypic characteristics, molecular signatures, and biological responses to external signals. Reconstruction of radiation responses in glioma stem cells is necessary for understanding the biological and molecular determinants of glioblastoma radioresistance. To date, there is a paucity of information on the longitudinal outcomes of hypofractionated radiation in glioma stem cells. This study addresses long-term outcomes of hypofractionated radiation in human glioma stem cells by using a combinatorial approach integrating parallel assessments of the tumor-propagating capacity, stemness-associated properties, and array-based profiling of gene expression. The study reveals a broad spectrum of changes in the tumor-propagating capacity of glioma stem cells after radiation and finds association with proliferative changes at the onset of differentiation. Evidence is provided that parallel transcriptomic patterns and a cumulative impact of pathways involved in the regulation of apoptosis, neural differentiation, and cell proliferation underly similarities in tumorigenicity changes after radiation.
NUDT7 Loss Promotes KrasG12D CRC Development
Authors: Song Jinsoo , Park Sujeong , Oh Jinjoo , Kim Deokha , Ryu Ji Hyun , Park Won Cheol , Baek In-Jeoung , Cheng Xi , Lu Xin , Jin Eun-Jung
Published: March 2020

Studies have suggested that dysregulation of peroxisomal lipid metabolism might play an important role in colorectal cancer (CRC) development. Here, we found that KrasG12D-driven CRC tumors demonstrate dysfunctional peroxisomal β-oxidation and identified Nudt7 (peroxisomal coenzyme A diphosphatase NUDT7) as one of responsible peroxisomal genes. In KrasG12D-driven CRC tumors, the expression level of Nudt7 was significantly decreased. Treatment of azoxymethane/dextran sulfate sodium (AOM/DSS) into Nudt7 knockout (Nudt7−/−) mice significantly induced lipid accumulation and the expression levels of CRC-related genes whereas xenografting of Nudt7-overexpressed LS-174T cells into mice significantly reduced lipid accumulation and the expression levels of CRC-related genes. Ingenuity pathway analysis of microarray using the colon of Nudt7−/− and Nudt7+/+ mice treated with AOM/DSS suggested Wnt signaling as one of activated signaling pathways in Nudt7−/− colons. Upregulated levels of β-catenin were observed in the colons of KrasG12D and AOM/DSS-treated Nudt7−/− mice and downstream targets of β-catenin such as Myc, Ccdn1, and Nos2, were also significantly increased in the colon of Nudt7−/− mice. We observed an increased level of palmitic acid in the colon of Nudt7−/− mice and attachment of palmitic acid-conjugated chitosan patch into the colon of mice induced the expression levels of β-catenin and CRC-related genes. Overall, our data reveal a novel role for peroxisomal NUDT7 in KrasG12D-driven CRC development.
Glioma Grading via Analysis of Digital Pathology Images Using Machine Learning
Authors: Rathore Saima , Niazi Tamim , Iftikhar Muhammad Aksam , Chaddad Ahmad
Published: March 2020

Cancer pathology reflects disease progression (or regression) and associated molecular characteristics, and provides rich phenotypic information that is predictive of cancer grade and has potential implications in treatment planning and prognosis. According to the remarkable performance of computational approaches in the digital pathology domain, we hypothesized that machine learning can help to distinguish low-grade gliomas (LGG) from high-grade gliomas (HGG) by exploiting the rich phenotypic information that reflects the microvascular proliferation level, mitotic activity, presence of necrosis, and nuclear atypia present in digital pathology images. A set of 735 whole-slide digital pathology images of glioma patients (median age: 49.65 years, male: 427, female: 308, median survival: 761.26 days) were obtained from TCGA. Sub-images that contained a viable tumor area, showing sufficient histologic characteristics, and that did not have any staining artifact were extracted. Several clinical measures and imaging features, including conventional (intensity, morphology) and advanced textures features (gray-level co-occurrence matrix and gray-level run-length matrix), extracted from the sub-images were further used for training the support vector machine model with linear configuration. We sought to evaluate the combined effect of conventional imaging, clinical, and texture features by assessing the predictive value of each feature type and their combinations through a predictive classifier. The texture features were successfully validated on the glioma patients in 10-fold cross-validation (accuracy = 75.12%, AUC = 0.652). The addition of texture features to clinical and conventional imaging features improved grade prediction compared to the models trained on clinical and conventional imaging features alone (p = 0.045 and p = 0.032 for conventional imaging features and texture features, respectively). The integration of imaging, texture, and clinical features yielded a significant improvement in accuracy, supporting the synergistic value of these features in the predictive model. The findings suggest that the texture features, when combined with conventional imaging and clinical markers, may provide an objective, accurate, and integrated prediction of glioma grades. The proposed digital pathology imaging-based marker may help to (i) stratify patients into clinical trials, (ii) select patients for targeted therapies, and (iii) personalize treatment planning on an individual person basis.
The Effect of Temperature and Time of the Hydrothermal Treatment in the SBA-15 Synthesis Process on the Structure and Textural Properties and the Ability to Reduce the Evolution of Tars in Tobacco Smoking
Authors: Juárez-Serrano Nerea , Asensio Javier , Martínez-Castellanos Isabel , Beltrán Maribel , Marcilla Antonio
Published: March 2020

Different SBA-15 (SBA, Santa Barbara Amorphous) materials were synthetized at different temperature and time during of the hydrothermal treatment. The obtained SBA-15 were characterized by N2 adsorption isotherms, scanning electron microscopy (SEM), X-ray diffraction (DRX), and density in order to establish the influence of these variables on their properties. Mixtures of the obtained catalysts with 3R4F tobacco were prepared and smoked under the ISO 3308 conditions. Temperature of the hydrothermal treatment slightly affects the tars that evolved in the smoking process of the corresponding catalyst tobacco mixtures. Contrarily, the time of the hydrothermal treatment has a marked effect on the reductions of toxic compounds in the smoke. Developed porosity has a positive correlation with the observed tar reduction, whereas the apparent density has a negative correlation with the reduction in toxicity. Moreover, the removal of the supernatant liquors during the hydrothermal treatment does not strongly modify the properties of the materials and may represent an interesting simplification of the process.
Ultrasonication-Assisted Synthesis of ZnxCd1−xS for Enhanced Visible-Light Photocatalytic Activity
Authors: Yang Lei , Zhang Maolin , Liu Mingzhu , Fan You , Ben Haijie , Li Longfeng , Fu Xianliang , Chen Shifu
Published: March 2020

ZnxCd1−xS as a solid solution photocatalyst has attracted widespread attention for its unique adjustable band gap structure and good and stable performance. A novel synthesis approach for ZnxCd1−xS is still required to further improve its performance. In this study, we synthesized a series of ZnxCd1−xS (x = 0−1) solid solutions via an ultrasonication-assisted hydrothermal route. In comparison with conventional methods of preparation, the sample prepared by our innovative method showed enhanced photocatalytic activity for the degradation of a methyl orange (MO) solution under visible light due to its high crystallinity and small crystallite size. Furthermore, the composition and bandgap of ZnxCd1−xS can be tuned by adjusting the mole ratio of Zn2+/Cd2+. Zn0.3Cd0.7S shows the highest level of activity and stability for the degradation of MO with k = 0.85 h−1, which is 2.2 times higher than that of CdS. The balance between band gap structure-directed redox capacity and light absorption of Zn0.3Cd0.7S accounts for its high photocatalytic performance, both of which are determined by the composition of the solid solution. Also, a degradation mechanism of MO over the sample is tentatively proposed. This study demonstrates a new strategy to synthesize highly efficient sulfide photocatalysts.
Light-Mediated Control over TRPC3-Mediated NFAT Signaling
Authors: Graziani Annarita , Bacsa Bernadett , Krivic Denis , Wiedner Patrick , Curcic Sanja , Schindl Rainer , Tiapko Oleksandra , Groschner Klaus
Published: March 2020

Canonical transient receptor potential (TRPC) channels were identified as key players in maladaptive remodeling, with nuclear factor of activated T-cells (NFAT) transcription factors serving as downstream targets of TRPC-triggered Ca2+ entry in these pathological processes. Strikingly, the reconstitution of TRPC-NFAT signaling by heterologous expression yielded controversial results. Specifically, nuclear translocation of NFAT1 was found barely responsive to recombinant TRPC3, presumably based on the requirement of certain spatiotemporal signaling features. Here, we report efficient control of NFAT1 nuclear translocation in human embryonic kidney 293 (HEK293) cells by light, using a new photochromic TRPC benzimidazole activator (OptoBI-1) and a TRPC3 mutant with modified activator sensitivity. NFAT1 nuclear translocation was measured along with an all-optical protocol to record local and global Ca2+ pattern generated during light-mediated activation/deactivation cycling of TRPC3. Our results unveil the ability of wild-type TRPC3 to produce constitutive NFAT nuclear translocation. Moreover, we demonstrate that TRPC3 mutant that lacks basal activity enables spatiotemporally precise control over NFAT1 activity by photopharmacology. Our results suggest tight linkage between TRPC3 activity and NFAT1 nuclear translocation based on global cellular Ca2+ signals.
Cross-Presenting XCR1+ Dendritic Cells as Targets for Cancer Immunotherapy
Authors: Audsley Katherine M. , McDonnell Alison M. , Waithman Jason
Published: March 2020

The use of dendritic cells (DCs) to generate effective anti-tumor T cell immunity has garnered much attention over the last thirty-plus years. Despite this, limited clinical benefit has been demonstrated thus far. There has been a revival of interest in DC-based treatment strategies following the remarkable patient responses observed with novel checkpoint blockade therapies, due to the potential for synergistic treatment. Cross-presenting DCs are recognized for their ability to prime CD8+ T cell responses to directly induce tumor death. Consequently, they are an attractive target for next-generation DC-based strategies. In this review, we define the universal classification system for cross-presenting DCs, and the vital role of this subset in mediating anti-tumor immunity. Furthermore, we will detail methods of targeting these DCs both ex vivo and in vivo to boost their function and drive effective anti-tumor responses.
Mitochondrial Structure and Function in the Metabolic Myopathy Accompanying Patients with Critical Limb Ischemia
Authors: Groennebaek Thomas , Billeskov Tine Borum , Schytz Camilla Tvede , Jespersen Nichlas Riise , Bøtker Hans Erik , Olsen Rikke Kathrine Jentoft , Eldrup Nikolaj , Nielsen Joachim , Farup Jean , de Paoli Frank Vincenzo , Vissing Kristian
Published: March 2020

Mitochondrial dysfunction has been implicated as a central mechanism in the metabolic myopathy accompanying critical limb ischemia (CLI). However, whether mitochondrial dysfunction is directly related to lower extremity ischemia and the structural and molecular mechanisms underpinning mitochondrial dysfunction in CLI patients is not understood. Here, we aimed to study whether mitochondrial dysfunction is a distinctive characteristic of CLI myopathy by assessing mitochondrial respiration in gastrocnemius muscle from 14 CLI patients (65.3 ± 7.8 y) and 15 matched control patients (CON) with a similar comorbidity risk profile and medication regimen but without peripheral ischemia (67.4 ± 7.4 y). Furthermore, we studied potential structural and molecular mechanisms of mitochondrial dysfunction by measuring total, sub-population, and fiber-type-specific mitochondrial volumetric content and cristae density with transmission electron microscopy and by assessing mitophagy and fission/fusion-related protein expression. Finally, we asked whether commonly used biomarkers of mitochondrial content are valid in patients with cardiovascular disease. CLI patients exhibited inferior mitochondrial respiration compared to CON. This respiratory deficit was not related to lower whole-muscle mitochondrial content or cristae density. However, stratification for fiber types revealed ultrastructural mitochondrial alterations in CLI patients compared to CON. CLI patients exhibited an altered expression of mitophagy-related proteins but not fission/fusion-related proteins compared to CON. Citrate synthase, cytochrome c oxidase subunit IV (COXIV), and 3-hydroxyacyl-CoA dehydrogenase (β-HAD) could not predict mitochondrial content. Mitochondrial dysfunction is a distinctive characteristic of CLI myopathy and is not related to altered organelle content or cristae density. Our results link this intrinsic mitochondrial deficit to dysregulation of the mitochondrial quality control system, which has implications for the development of therapeutic strategies.
From Synthesis to Utilization: The Ins and Outs of Mitochondrial Heme
Authors: Swenson Samantha A. , Moore Courtney M. , Marcero Jason R. , Medlock Amy E. , Reddi Amit R. , Khalimonchuk Oleh
Published: March 2020

Heme is a ubiquitous and essential iron containing metallo-organic cofactor required for virtually all aerobic life. Heme synthesis is initiated and completed in mitochondria, followed by certain covalent modifications and/or its delivery to apo-hemoproteins residing throughout the cell. While the biochemical aspects of heme biosynthetic reactions are well understood, the trafficking of newly synthesized heme—a highly reactive and inherently toxic compound—and its subsequent delivery to target proteins remain far from clear. In this review, we summarize current knowledge about heme biosynthesis and trafficking within and outside of the mitochondria.
Electronegative LDL Promotes Inflammation and Triglyceride Accumulation in Macrophages
Authors: Puig Núria , Montolio Lara , Camps-Renom Pol , Navarra Laia , Jiménez-Altayó Francesc , Jiménez-Xarrié Elena , Sánchez-Quesada Jose Luis , Benitez Sonia
Published: March 2020

Electronegative low-density lipoprotein (LDL) (LDL(−)), a modified LDL that is present in blood and exerts atherogenic effects on endothelial cells and monocytes. This study aimed to determine the action of LDL(−) on monocytes differentiated into macrophages. LDL(−) and in vitro-modified LDLs (oxidized, aggregated, and acetylated) were added to macrophages derived from THP1 monocytes over-expressing CD14 (THP1-CD14). Then, cytokine release, cell differentiation, lipid accumulation, and gene expression were measured by ELISA, flow cytometry, thin-layer chromatography, and real-time PCR, respectively. LDL(−) induced more cytokine release in THP1-CD14 macrophages than other modified LDLs. LDL(−) also promoted morphological changes ascribed to differentiated macrophages. The addition of high-density lipoprotein (HDL) and anti-TLR4 counteracted these effects. LDL(−) was highly internalized by macrophages, and it was the major inductor of intracellular lipid accumulation in triglyceride-enriched lipid droplets. In contrast to inflammation, the addition of anti-TLR4 had no effect on lipid accumulation, thus suggesting an uptake pathway alternative to TLR4. In this regard, LDL(−) upregulated the expression of the scavenger receptors CD36 and LOX-1, as well as several genes involved in triglyceride (TG) accumulation. The importance and novelty of the current study is that LDL(−), a physiologically modified LDL, exerted atherogenic effects in macrophages by promoting differentiation, inflammation, and triglyceride-enriched lipid droplets formation in THP1-CD14 macrophages, probably through different receptors.
Signaling Pathways and Key Genes Involved in Regulation of foam Cell Formation in Atherosclerosis
Authors: Poznyak Anastasia V. , Wu Wei-Kai , Melnichenko Alexandra A. , Wetzker Reinhard , Sukhorukov Vasily , Markin Alexander M. , Khotina Victoria A. , Orekhov Alexander N.
Published: March 2020

Atherosclerosis is associated with acute cardiovascular conditions, such as ischemic heart disease, myocardial infarction, and stroke, and is the leading cause of morbidity and mortality worldwide. Our understanding of atherosclerosis and the processes triggering its initiation is constantly improving, and, during the last few decades, many pathological processes related to this disease have been investigated in detail. For example, atherosclerosis has been considered to be a chronic inflammation triggered by the injury of the arterial wall. However, recent works showed that atherogenesis is a more complex process involving not only the immune system, but also resident cells of the vessel wall, genetic factors, altered hemodynamics, and changes in lipid metabolism. In this review, we focus on foam cells that are crucial for atherosclerosis lesion formation. It has been demonstrated that the formation of foam cells is induced by modified low-density lipoprotein (LDL). The beneficial effects of the majority of therapeutic strategies with generalized action, such as the use of anti-inflammatory drugs or antioxidants, were not confirmed by clinical studies. However, the experimental therapies targeting certain stages of atherosclerosis, among which are lipid accumulation, were shown to be more effective. This emphasizes the relevance of future detailed investigation of atherogenesis and the importance of new therapies development.
The Potential of Computational Modeling to Predict Disease Course and Treatment Response in Patients with Relapsing Multiple Sclerosis
Authors: Pappalardo Francesco , Russo Giulia , Pennisi Marzio , Parasiliti Palumbo Giuseppe Alessandro , Sgroi Giuseppe , Motta Santo , Maimone Davide
Published: March 2020

As of today, 20 disease-modifying drugs (DMDs) have been approved for the treatment of relapsing multiple sclerosis (MS) and, based on their efficacy, they can be grouped into moderate-efficacy DMDs and high-efficacy DMDs. The choice of the drug mostly relies on the judgment and experience of neurologists and the evaluation of the therapeutic response can only be obtained by monitoring the clinical and magnetic resonance imaging (MRI) status during follow up. In an era where therapies are focused on personalization, this study aims to develop a modeling infrastructure to predict the evolution of relapsing MS and the response to treatments. We built a computational modeling infrastructure named Universal Immune System Simulator (UISS), which can simulate the main features and dynamics of the immune system activities. We extended UISS to simulate all the underlying MS pathogenesis and its interaction with the host immune system. This simulator is a multi-scale, multi-organ, agent-based simulator with an attached module capable of simulating the dynamics of specific biological pathways at the molecular level. We simulated six MS patients with different relapsing–remitting courses. These patients were characterized based on their age, sex, presence of oligoclonal bands, therapy, and MRI lesion load at the onset. The simulator framework is made freely available and can be used following the links provided in the availability section. Even though the model can be further personalized employing immunological parameters and genetic information, we generated a few simulation scenarios for each patient based on the available data. Among these simulations, it was possible to find the scenarios that realistically matched the real clinical and MRI history. Moreover, for two patients, the simulator anticipated the timing of subsequent relapses, which occurred, suggesting that UISS may have the potential to assist MS specialists in predicting the course of the disease and the response to treatment.
Vertically Coupling ZnO Nanorods onto MoS2 Flakes for Optical Gas Sensing
Authors: Faglia Guido , Ferroni Matteo , Dang Thi Thanh Le , Donarelli Maurizio , Rigoni Federica , Baratto Camilla
Published: March 2020

Hybrid structures composed of layered one-dimensional (1D) and two-dimensional (2D) materials opened new perspectives and opportunities through the build-up of hetero-junctions with versatile layered structures and led to fascinating fundamental phenomena and advanced devices. We succeeded in depositing by magnetron sputtering vertically aligned 1D ZnO nanorods on 2D MoS2 flakes obtained by exfoliation, preserving the structure of the 2D materials. The photoluminescence (PL) optical properties of the hybrid structure were assessed towards developing a contactless optical chemical sensor.
Reliability, Consistency and Temporal Stability of Alberta Infant Motor Scale in Serbian Infants
Authors: Lackovic Milan , Nikolic Dejan , Filimonovic Dejan , Petronic Ivana , Mihajlovic Sladjana , Golubovic Zoran , Pavicevic Polina , Cirovic Dragana
Published: March 2020

Our study aimed to analyze the reliability, consistency, and temporal stability of the Alberta Infant Motor Scale (AIMS) in Serbian infants. Additionally, we aimed to present a percentile distribution of AIMS in the tested population. The prospective study included 60 infants that were divided into three age groups: 0–3 months, 4–7 months, and 8–14 months. The Serbian version of AIMS was tested by two raters on two different occasions (test/retest) with a five day period between tests. The observed inter-rater reliability (intraclass correlation coefficient (ICC)) was more than 0.75 for all AIMS scores, except for standing (ICC 0.655 = moderate) in the age group of 4–7 months on retest between raters. The observed intra-rater reliability (ICC) was more than 0.75 for all AIMS scores except standing (ICC 0.655 = moderate) in the age group 4–7 months in test–retest for Rater One, and for sitting (ICC 0.671 = moderate) and standing (ICC 0.725 = moderate) in the age group between 0–3 months on test–retest for Rater Two. The Serbian version of AIMS was shown to have high consistency and high reliability with good to high temporal stability. Thus, it can be used in the evaluation of infants’ motor development in Serbia.
Effect of Ultrafine Grains on the Coating Reaction and Anticorrosion Performance of Anodized Pure Aluminum
Authors: Wang Guowei , Song Dan , Zhou Zhikai , Klu Edwin Eyram , Liu Yi , Liang Ningning , Jiang Jinghua , Sun Jiapeng , Ma Aibin
Published: March 2020

This work analyzes the effects of ultrafine aluminum (Al) grains on the anodizing coating reaction and anticorrosion performance of anodized industrial pure Al. Equal-channel angular pressing (ECAP) was applied to cast pure Al continuously for 16 passes at room temperature, and its average grain size was dramatically refined to about 1.5 μm. The ultrafine-grain (UFG) pure Al was further anodized with a cast sample via a parallel anodizing circuit at a constant total input current. Benefited by the higher volume fraction of grain boundaries and higher internal energy of the UFG substrate, the anodizing process of the ECAP-processed pure Al was significantly accelerated, showing a more intense initial anodizing reaction, a faster initial coating thickening, and much earlier porous-layer formation compared to the cast sample. As the anodizing reaction continued, the newly formed thicker coating of the ECAP-coated sample significantly hindered the diffusion process, weakening the thermodynamic advantage and decreasing the anodizing current of the ECAP-processed sample. During the entire anodizing duration, the ECAP-processed pure Al experienced gradually decreased anodizing current, while the cast sample experienced increased anodizing current. Because of the more total reaction, the ECAP-coated sample always maintained a relatively thicker coating and better anticorrosion performance during the entire anodizing duration.
Friction Reduction in Unidirectional Lubricated Sliding Due to Disc Surface Texturing
Authors: Wos Slawomir , Koszela Waldemar , Dzierwa Andrzej , Pawlus Pawel
Published: March 2020

Surface texturing is an option of surface engineering resulting in reduction of friction due to the creation of isolated dimples or grooves on sliding surfaces. The purpose of this work is to find the effect of the groove bottom profiles on the reduction of the friction force. Investigations were conducted using an Optimol SRV5 tribotester equipped with a pin-on-disc module. A disc made of 42CrMo4 steel, with a 100 mm diameter acted as a sample. A counter-sample was made of the same material, however, its diameter was 20 mm. The sliding conditions were selected to be similar to those of a sliding crankpin bearing pad operating in a high-performance internal combustion engine. Surface texturing was found to be beneficial for a reduction in the friction coefficient up to 55% in comparison to the untextured disc. Tribological performances of discs with spiral groove patterns were better than those with a radial layout. In most cases the convergent profile of the groove bottom was superior to the dam shape.
Preparation of Plasmonic Au-TiO2 Thin Films on a Transparent Polymer Substrate
Authors: Rodrigues Marco S. , Meira Diana I. , Lopes Cláudia , Borges Joel , Vaz Filipe
Published: March 2020

In this work, plasmonic thin films composed of Au nanoparticles embedded in a TiO2 matrix were prepared in a transparent polymer substrate of poly(dimethylsiloxane) (PDMS). The thin films were deposited by reactive DC magnetron sputtering, and then subjected to heat treatment up to 150 °C in order to promote the growth of the Au nanoparticles throughout the TiO2 matrix. The transmittance spectrum of the thin films was monitored in situ during the heat treatment, and the minimum time required to have a defined localized surface plasmon resonance (LSPR) band was about 10 min. The average size of Au nanoparticles was estimated to be about 21 nm—the majority of them are sized in the range 10–40 nm, but also extend to larger sizes, with irregular shapes. The refractive index sensitivity of the films was estimated by using two test fluids (H2O and DMSO), and the average value reached in the assays was 37.3 ± 1.5 nm/RIU, resulting from an average shift of 5.4 ± 0.2 nm. The results show that it is possible to produce sensitive plasmonic Au-TiO2 thin films in transparent polymer substrates such as PDMS, the base material to develop microfluidic channels to be incorporated in LSPR sensing systems.
The Expansion of Cholangioscopy: Established and Investigational Uses of SpyGlass in Biliary and Pancreatic Disorders
Authors: Yodice Michael , Choma Joseph , Tadros Micheal
Published: March 2020

Direct visualization of bile and pancreatic duct pathology is proving to be beneficial in patients where previous techniques have failed. Recent advancements in technology and the development of the SpyGlass system have led to an increased use of cholangioscopy. It is already known that SpyGlass is beneficial in patients with difficult bile duct stones and indeterminate biliary lesions through the use of targeted lithotripsy and visually guided biopsy. Cholangioscopy allows the visualization of hidden stone and guide wire placement across difficult strictures and selective cannulation of the intrahepatic and cystic ducts. It is also demonstrating its utility in investigational applications such as post-liver transplant and primary sclerosing cholangitis stricture treatment, evaluation of hemobilia, and guided radiofrequency ablation of ductal tumors. In addition to having clinical utility, cholangioscopy may also be cost-effective by limiting the number of repeat procedures. Cholangioscopy overall has similar complication rates compared to other standard endoscopic retrograde cholangioscopy (ERCP) techniques, but there may be higher rates of cholangitis. This could be mitigated with prophylactic antibiotic use, and overall, cholangioscopy has similar complication rates compared to other techniques.
Applying the Bell’s Test to Chinese Texts
Authors: Bessmertny Igor A. , Huang Xiaoxi , Platonov Aleksei V. , Yu Chuqiao , Koroleva Julia A.
Published: March 2020

Search engines are able to find documents containing patterns from a query. This approach can be used for alphabetic languages such as English. However, Chinese is highly dependent on context. The significant problem of Chinese text processing is the missing blanks between words, so it is necessary to segment the text to words before any other action. Algorithms for Chinese text segmentation should consider context; that is, the word segmentation process depends on other ideograms. As the existing segmentation algorithms are imperfect, we have considered an approach to build the context from all possible n-grams surrounding the query words. This paper proposes a quantum-inspired approach to rank Chinese text documents by their relevancy to the query. Particularly, this approach uses Bell’s test, which measures the quantum entanglement of two words within the context. The contexts of words are built using the hyperspace analogue to language (HAL) algorithm. Experiments fulfilled in three domains demonstrated that the proposed approach provides acceptable results.
Traveling-Wave Convection with Periodic Source Defects in Binary Fluid Mixtures with Strong Soret Effect
Authors: Zheng Laiyun , Zhao Bingxin , Yang Jianqing , Tian Zhenfu , Ye Ming
Published: March 2020

This paper studied the Rayleigh–Bénard convection in binary fluid mixtures with a strong Soret effect (separation ratio ψ = − 0.6 ) in a rectangular container heated uniformly from below. We used a high-accuracy compact finite difference method to solve the hydrodynamic equations used to describe the Rayleigh–Bénard convection. A stable traveling-wave convective state with periodic source defects (PSD-TW) is obtained and its properties are discussed in detail. Our numerical results show that the novel PSD-TW state is maintained by the Eckhaus instability and the difference between the creation and annihilation frequencies of convective rolls at the left and right boundaries of the container. In the range of Rayleigh number in which the PSD-TW state is stable, the period of defect occurrence increases first and then decreases with increasing Rayleigh number. At the upper bound of this range, the system transitions from PSD-TW state to another type of traveling-wave state with aperiodic and more dislocated defects. Moreover, we consider the problem with the Prandtl number P r ranging from 0.1 to 20 and the Lewis number L e from 0.001 to 1, and discuss the stabilities of the PSD-TW states and present the results as phase diagrams.
IMMIGRATE: A Margin-Based Feature Selection Method with Interaction Terms
Authors: Zhao Ruzhang , Hong Pengyu , Liu Jun S.
Published: March 2020

Traditional hypothesis-margin researches focus on obtaining large margins and feature selection. In this work, we show that the robustness of margins is also critical and can be measured using entropy. In addition, our approach provides clear mathematical formulations and explanations to uncover feature interactions, which is often lack in large hypothesis-margin based approaches. We design an algorithm, termed IMMIGRATE (Iterative max-min entropy margin-maximization with interaction terms), for training the weights associated with the interaction terms. IMMIGRATE simultaneously utilizes both local and global information and can be used as a base learner in Boosting. We evaluate IMMIGRATE in a wide range of tasks, in which it demonstrates exceptional robustness and achieves the state-of-the-art results with high interpretability.
Knowledge, Attitude and Perception of Risk and Preventive Behaviors toward Premarital Sexual Practice among In-School Adolescents
Authors: YAU Shamsudeen , Wongsawat Pramote , Songthap Archin
Published: March 2020

Premarital Sexual Practice (PSP) among adolescents usually involves sexually risky behaviors, such as multiple sexual partners and inconsistent or non-condom use. These behaviors, in combination with other underlining factors, undermine the overall outcomes of Adolescent Sexual and Reproductive Health (ASRH). To assess the adolescents’ knowledge, attitudes and perception of risk and preventive behaviors towards PSP, a school-based analytical cross-sectional study was conducted among a sample of 423 students aged 15 through 19 years. A well-validated anonymous self-administered questionnaire was used for collecting the data, which were analyzed using mean (SD), frequency (%), t-test, ANOVA and multiple regression methods. Participants’ knowledge of risk and preventive behaviors was average, as only 53% of knowledge items were correctly answered. Being a female, of high-income status, in the second study year, perceived susceptibility and perceived severity were significant determinants of knowledge. All measures of perception except perceived self-efficacy were positive determinants of attitude. Being female, in the third study year and of high-income status were determinants of perception as measured by perceived self-efficacy. Therefore, our results suggest that tailored educational programs, with special emphasis on financially disadvantaged male adolescents, are needed to effectively increase adolescents’ knowledge, attitude and perception of risk and protective behaviors towards PSP.
Electrochem: An International Scientific Open Access Journal to Publish All Faces of Electrochemistry, Electrodeposition, Electrochemical Analysis, Electrochemical Sensing and Other Aspects about Electrochemical Reaction
Authors: Sone Masato
Published: March 2020

Our aim of journal Electrochem is to provide reviews, regular research papers, and communications in all areas of electrochemistry including methodologies, techniques, and instrumentation in both fundamental and applied fields. In this Editorial, the various technological demands for electrochemistry from academic and industrial fields are discussed and some problems to be solved in electrochemistry are proposed for next-generation science and technology. Under these technological demands, open access journals such as Electrochem will provide the solutions and new technology in electrochemistry to the world.