bluuebunny/crossref_metadata_2025 huggingface dataset:
Retinal Molecular Changes Are Associated with Neuroinflammation and Loss of RGCs in an Experimental Model of Glaucoma
Authors: Fernández-Albarral José A. , Salazar Juan J. , de Hoz Rosa , Marco Eva M. , Martín-Sánchez Beatriz , Flores-Salguero Elena , Salobrar-García Elena , López-Cuenca Inés , Barrios-Sabador Vicente , Avilés-Trigueros Marcelino , Valiente-Soriano Francisco J. , Miralles de Imperial-Ollero Juan A. , Vidal-Sanz Manuel , Triviño Alberto , Ramírez José M. , López-Gallardo Meritxell , Ramírez Ana I.
Published: February 2021

Signaling mediated by cytokines and chemokines is involved in glaucoma-associated neuroinflammation and in the damage of retinal ganglion cells (RGCs). Using multiplexed immunoassay and immunohistochemical techniques in a glaucoma mouse model at different time points after ocular hypertension (OHT), we analyzed (i) the expression of pro-inflammatory cytokines, anti-inflammatory cytokines, BDNF, VEGF, and fractalkine; and (ii) the number of Brn3a+ RGCs. In OHT eyes, there was an upregulation of (i) IFN-γ at days 3, 5, and 15; (ii) IL-4 at days 1, 3, 5, and 7 and IL-10 at days 3 and 5 (coinciding with downregulation of IL1-β at days 1, 5, and 7); (iii) IL-6 at days 1, 3, and 5; (iv) fractalkine and VEGF at day 1; and (v) BDNF at days 1, 3, 7, and 15. In contralateral eyes, there were (i) an upregulation of IL-1β at days 1 and 3 and a downregulation at day 7, coinciding with the downregulation of IL4 at days 3 and 5 and the upregulation at day 7; (ii) an upregulation of IL-6 at days 1, 5, and 7 and a downregulation at 15 days; (iii) an upregulation of IL-10 at days 3 and 7; and (iv) an upregulation of IL-17 at day 15. In OHT eyes, there was a reduction in the Brn3a+ RGCs number at days 3, 5, 7, and 15. OHT changes cytokine levels in both OHT and contralateral eyes at different time points after OHT induction, confirming the immune system involvement in glaucomatous neurodegeneration.
Therapeutic Targeting of the Tumour Microenvironment in Metastatic Colorectal Cancer
Authors: Dmello Rhynelle S. , To Sarah Q. , Chand Ashwini L.
Published: February 2021

Liver metastasis is the primary contributor to the death of patients with colorectal cancer. Despite the overall success of current treatments including targeted therapy, chemotherapy, and immunotherapy combinations in colorectal cancer patients, the prognosis of patients with liver metastasis remains poor. Recent studies have highlighted the importance of the tumour microenvironment and the crosstalk within that determines the fate of circulating tumour cells in distant organs. Understanding the interactions between liver resident cells and tumour cells colonising the liver opens new therapeutic windows for the successful treatment of metastatic colorectal cancer. Here we discuss critical cellular interactions within the tumour microenvironment in primary tumours and in liver metastases that highlight potential therapeutic targets. We also discuss recent therapeutic advances for the treatment of metastatic colorectal cancer.
AdipoRon Treatment Induces a Dose-Dependent Response in Adult Hippocampal Neurogenesis
Authors: Lee Thomas H. , Christie Brian R. , van Praag Henriette , Lin Kangguang , Siu Parco Ming-Fai , Xu Aimin , So Kwok-Fai , Yau Suk-yu
Published: February 2021

AdipoRon, an adiponectin receptor agonist, elicits similar antidiabetic, anti-atherogenic, and anti-inflammatory effects on mouse models as adiponectin does. Since AdipoRon can cross the blood-brain barrier, its chronic effects on regulating hippocampal function are yet to be examined. This study investigated whether AdipoRon treatment promotes hippocampal neurogenesis and spatial recognition memory in a dose-dependent manner. Adolescent male C57BL/6J mice received continuous treatment of either 20 mg/kg (low dose) or 50 mg/kg (high dose) AdipoRon or vehicle intraperitoneally for 14 days, followed by the open field test to examine anxiety and locomotor activity, and the Y maze test to examine hippocampal-dependent spatial recognition memory. Immunopositive cell markers of neural progenitor cells, immature neurons, and newborn cells in the hippocampal dentate gyrus were quantified. Immunosorbent assays were used to measure the serum levels of factors that can regulate hippocampal neurogenesis, including adiponectin, brain-derived neurotrophic factor (BDNF), and corticosterone. Our results showed that 20 mg/kg AdipoRon treatment significantly promoted hippocampal cell proliferation and increased serum levels of adiponectin and BDNF, though there were no effects on spatial recognition memory and locomotor activity. On the contrary, 50 mg/kg AdipoRon treatment impaired spatial recognition memory, suppressed cell proliferation, neuronal differentiation, and cell survival associated with reduced serum levels of BDNF and adiponectin. The results suggest that a low-dose AdipoRon treatment promotes hippocampal cell proliferation, while a high-dose AdipoRon treatment is detrimental to the hippocampus function.
Cardioprotective Effects of a Nonsteroidal Mineralocorticoid Receptor Blocker, Esaxerenone, in Dahl Salt-Sensitive Hypertensive Rats
Authors: Rahman Asadur , Sawano Tatsuya , Sen Anupoma , Hossain Akram , Jahan Nourin , Kobara Hideki , Masaki Tsutomu , Kosaka Shinji , Kitada Kento , Nakano Daisuke , Imamura Takeshi , Ohsaki Hiroyuki , Nishiyama Akira
Published: February 2021

We investigated the effects of esaxerenone, a novel, nonsteroidal, and selective mineralocorticoid receptor blocker, on cardiac function in Dahl salt-sensitive (DSS) rats. We provided 6-week-old DSS rats a high-salt diet (HSD, 8% NaCl). Following six weeks of HSD feeding (establishment of cardiac hypertrophy), we divided the animals into the following two groups: HSD or HSD + esaxerenone (0.001%, w/w). In survival study, all HSD-fed animals died by 24 weeks of age, whereas the esaxerenone-treated HSD-fed animals showed significantly improved survival. We used the same protocol with a separate set of animals to evaluate the cardiac function by echocardiography after four weeks of treatment. The results showed that HSD-fed animals developed cardiac dysfunction as evidenced by reduced stroke volume, ejection fraction, and cardiac output. Importantly, esaxerenone treatment decreased the worsening of cardiac dysfunction concomitant with a significantly reduced level of systolic blood pressure. In addition, treatment with esaxerenone in HSD-fed DSS rats caused a reduced level of cardiac remodeling as well as fibrosis. Furthermore, inflammation and oxidative stress were significantly reduced. These data indicate that esaxerenone has the potential to mitigate cardiac dysfunction in salt-induced myocardial injury in rats.
Statin-Induced Myopathy: Translational Studies from Preclinical to Clinical Evidence
Authors: Camerino Giulia Maria , Tarantino Nancy , Canfora Ileana , De Bellis Michela , Musumeci Olimpia , Pierno Sabata
Published: February 2021

Statins are the most prescribed and effective drugs to treat cardiovascular diseases (CVD). Nevertheless, these drugs can be responsible for skeletal muscle toxicity which leads to reduced compliance. The discontinuation of therapy increases the incidence of CVD. Thus, it is essential to assess the risk. In fact, many studies have been performed at preclinical and clinical level to investigate pathophysiological mechanisms and clinical implications of statin myotoxicity. Consequently, new toxicological aspects and new biomarkers have arisen. Indeed, these drugs may affect gene transcription and ion transport and contribute to muscle function impairment. Identifying a marker of toxicity is important to prevent or to cure statin induced myopathy while assuring the right therapy for hypercholesterolemia and counteracting CVD. In this review we focused on the mechanisms of muscle damage discovered in preclinical and clinical studies and highlighted the pathological situations in which statin therapy should be avoided. In this context, preventive or substitutive therapies should also be evaluated.
Ex uno, plures–From One Tissue to Many Cells: A Review of Single-Cell Transcriptomics in Cardiovascular Biology
Authors: Forte Elvira , McLellan Micheal A. , Skelly Daniel A. , Rosenthal Nadia A.
Published: February 2021

Recent technological advances have revolutionized the study of tissue biology and garnered a greater appreciation for tissue complexity. In order to understand cardiac development, heart tissue homeostasis, and the effects of stress and injury on the cardiovascular system, it is essential to characterize the heart at high cellular resolution. Single-cell profiling provides a more precise definition of tissue composition, cell differentiation trajectories, and intercellular communication, compared to classical bulk approaches. Here, we aim to review how recent single-cell multi-omic studies have changed our understanding of cell dynamics during cardiac development, and in the healthy and diseased adult myocardium.
Repetitive Elements in Humans
Authors: Liehr Thomas
Published: February 2021

Repetitive DNA in humans is still widely considered to be meaningless, and variations within this part of the genome are generally considered to be harmless to the carrier. In contrast, for euchromatic variation, one becomes more careful in classifying inter-individual differences as meaningless and rather tends to see them as possible influencers of the so-called ‘genetic background’, being able to at least potentially influence disease susceptibilities. Here, the known ‘bad boys’ among repetitive DNAs are reviewed. Variable numbers of tandem repeats (VNTRs = micro- and minisatellites), small-scale repetitive elements (SSREs) and even chromosomal heteromorphisms (CHs) may therefore have direct or indirect influences on human diseases and susceptibilities. Summarizing this specific aspect here for the first time should contribute to stimulating more research on human repetitive DNA. It should also become clear that these kinds of studies must be done at all available levels of resolution, i.e., from the base pair to chromosomal level and, importantly, the epigenetic level, as well.
Fargesin Inhibits EGF-Induced Cell Transformation and Colon Cancer Cell Growth by Suppression of CDK2/Cyclin E Signaling Pathway
Authors: Lee Ga-Eun , Lee Cheol-Jung , An Hyun-Jung , Kang Han Chang , Lee Hye Suk , Lee Joo Young , Oh Sei-Ryang , Cho Sung-Jun , Kim Dae Joon , Cho Yong-Yeon
Published: February 2021

Although the lignan compound fargesin is a major ingredient in Shin-Yi, the roles of fargesin in carcinogenesis and cancer cell growth have not been elucidated. In this study, we observed that fargesin inhibited cell proliferation and transformation by suppression of epidermal growth factor (EGF)-stimulated G1/S-phase cell cycle transition in premalignant JB6 Cl41 and HaCaT cells. Unexpectedly, we found that signaling pathway analyses showed different regulation patterns in which fargesin inhibited phosphatidylinositol 3-kinase/AKT signaling without an alteration of or increase in mitogen activated protein kinase (MAPK) in JB6 Cl41 and HaCaT cells, while both signaling pathways were abrogated by fargesin treatment in colon cancer cells. We further found that fargesin-induced colony growth inhibition of colon cancer cells was mediated by suppression of the cyclin dependent kinase 2 (CDK2)/cyclin E signaling axis by upregulation of p21WAF1/Cip1, resulting in G1-phase cell cycle accumulation in a dose-dependent manner. Simultaneously, the suppression of CDK2/cyclin E and induction of p21WAF1/Cip1 were correlated with Rb phosphorylation and c-Myc suppression. Taken together, we conclude that fargesin-mediated c-Myc suppression inhibits EGF-induced cell transformation and colon cancer cell colony growth by the suppression of retinoblastoma (Rb)-E2F and CDK/cyclin signaling pathways, which are mainly regulated by MAPK and PKB signaling pathways.
Changes in Apoptotic Pathways in MOLM-13 Cell Lines after Induction of Resistance to Hypomethylating Agents
Authors: Janotka Ľuboš , Messingerová Lucia , Šimoničová Kristína , Kavcová Helena , Elefantová Katarína , Sulová Zdena , Breier Albert
Published: February 2021

We established the following two variants of the MOLM-13 human acute myeloid leukemia (AML) cell line: (i) MOLM-13/DAC cells are resistant to 5-aza-2′-deoxycytidine (DAC), and (ii) MOLM-13/AZA are resistant to 5-azacytidine (AZA). Both cell variants were obtained through a six-month selection/adaptation procedure with a stepwise increase in the concentration of either DAC or AZA. MOLM-13/DAC cells are resistant to DAC, and MOLM-13/AZA cells are resistant to AZA (approximately 50-fold and 20-fold, respectively), but cross-resistance of MOLM-13/DAC to AZA and of MOLM-13/AZA to DAC was not detected. By measuring the cell retention of fluorescein-linked annexin V and propidium iodide, we showed an apoptotic mode of death for MOLM-13 cells after treatment with either DAC or AZA, for MOLM-13/DAC cells after treatment with AZA, and for MOLM-13/AZA cells after treatment with DAC. When cells progressed to apoptosis, via JC-1 (5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethyl-imidacarbocyanine iodide) assay, we detected a reduction in the mitochondrial membrane potential. Furthermore, we characterized promoter methylation levels for some genes encoding proteins regulating apoptosis and the relation of this methylation to the expression of the respective genes. In addition, we focused on determining the expression levels and activity of intrinsic and extrinsic apoptosis pathway proteins.
How Is the Fidelity of Proteins Ensured in Terms of Both Quality and Quantity at the Endoplasmic Reticulum? Mechanistic Insights into E3 Ubiquitin Ligases
Authors: Kang Ji An , Jeon Young Joo
Published: February 2021

The endoplasmic reticulum (ER) is an interconnected organelle that plays fundamental roles in the biosynthesis, folding, stabilization, maturation, and trafficking of secretory and transmembrane proteins. It is the largest organelle and critically modulates nearly all aspects of life. Therefore, in the endoplasmic reticulum, an enormous investment of resources, including chaperones and protein folding facilitators, is dedicated to adequate protein maturation and delivery to final destinations. Unfortunately, the folding and assembly of proteins can be quite error-prone, which leads to the generation of misfolded proteins. Notably, protein homeostasis, referred to as proteostasis, is constantly exposed to danger by flows of misfolded proteins and subsequent protein aggregates. To maintain proteostasis, the ER triages and eliminates terminally misfolded proteins by delivering substrates to the ubiquitin–proteasome system (UPS) or to the lysosome, which is termed ER-associated degradation (ERAD) or ER-phagy, respectively. ERAD not only eliminates misfolded or unassembled proteins via protein quality control but also fine-tunes correctly folded proteins via protein quantity control. Intriguingly, the diversity and distinctive nature of E3 ubiquitin ligases determine efficiency, complexity, and specificity of ubiquitination during ERAD. ER-phagy utilizes the core autophagy machinery and eliminates ERAD-resistant misfolded proteins. Here, we conceptually outline not only ubiquitination machinery but also catalytic mechanisms of E3 ubiquitin ligases. Further, we discuss the mechanistic insights into E3 ubiquitin ligases involved in the two guardian pathways in the ER, ERAD and ER-phagy. Finally, we provide the molecular mechanisms by which ERAD and ER-phagy conduct not only protein quality control but also protein quantity control to ensure proteostasis and subsequent organismal homeostasis.
Potassium Channels Kv1.3 and Kir2.1 But Not Kv1.5 Contribute to BV2 Cell Line and Primary Microglial Migration
Authors: Anton Ruxandra , Ghenghea Mihail , Ristoiu Violeta , Gattlen Christophe , Suter Marc-Rene , Cojocaru Petre Alexandru , Popa-Wagner Aurel , Catalin Bogdan , Deftu Alexandru-Florian
Published: February 2021

(1) Background: As membrane channels contribute to different cell functions, understanding the underlying mechanisms becomes extremely important. A large number of neuronal channels have been investigated, however, less studied are the channels expressed in the glia population, particularly in microglia. In the present study, we focused on the function of the Kv1.3, Kv1.5 and Kir2.1 potassium channels expressed in both BV2 cells and primary microglia cultures, which may impact the cellular migration process. (2) Methods: Using an immunocytochemical approach, we were able to show the presence of the investigated channels in BV2 microglial cells, record their currents using a patch clamp and their role in cell migration using the scratch assay. The migration of the primary microglial cells in culture was assessed using cell culture inserts. (3) Results: By blocking each potassium channel, we showed that Kv1.3 and Kir2.1 but not Kv1.5 are essential for BV2 cell migration. Further, primary microglial cultures were obtained from a line of transgenic CX3CR1-eGFP mice that express fluorescent labeled microglia. The mice were subjected to a spared nerve injury model of pain and we found that microglia motility in an 8 µm insert was reduced 2 days after spared nerve injury (SNI) compared with sham conditions. Additional investigations showed a further impact on cell motility by specifically blocking Kv1.3 and Kir2.1 but not Kv1.5; (4) Conclusions: Our study highlights the importance of the Kv1.3 and Kir2.1 but not Kv1.5 potassium channels on microglia migration both in BV2 and primary cell cultures.
Titanium Dioxide, but Not Zinc Oxide, Nanoparticles Cause Severe Transcriptomic Alterations in T98G Human Glioblastoma Cells
Authors: Fuster Encarnación , Candela Héctor , Estévez Jorge , Vilanova Eugenio , Sogorb Miguel A.
Published: February 2021

Titanium dioxide and zinc oxide are two of the most widely used nanomaterials. We assessed the effects of noncytotoxic doses of both nanomaterials on T98G human glioblastoma cells by omic approaches. Surprisingly, no effects on the transcriptome of T98G cells was detected after exposure to 5 µg/mL of zinc oxide nanoparticles during 72 h. Conversely, the transcriptome of the cells exposed to 20 µg/mL of titanium dioxide nanoparticles during 72 h revealed alterations in lots of biological processes and molecular pathways. Alterations to the transcriptome suggests that exposure to titanium dioxide nanoparticles might, potentially, compromise the integrity of the blood brain barrier integrity and cause neuroinflammation. The latter issue was further confirmed phenotypically with a proteomic analysis and by recording the release of interleukin 8. Titanium dioxide also caused autophagy, which was demonstrated through the increase in the expression of the autophagy-related 3 and microtubule associated protein 1 light chain 3 alpha genes. The proteomic analysis revealed that titanium dioxide nanoparticles might have anticancerigen properties by downregulating genes involved in the detoxication of anthracyclines. A risk assessment resulting from titanium dioxide exposure, focusing on the central nervous system as a potential target of toxicity, is necessary.
De Novo Transcriptome Assembly of Two Microsorum Fern Species Identifies Enzymes Required for Two Upstream Pathways of Phytoecdysteroids
Authors: Sripinyowanich Siriporn , Kil Eui-Joon , Petchsri Sahanat , Jo Yeonhwa , Choi Hoseong , Cho Won Kyong , Lee Sukchan
Published: February 2021

Microsorum species produce a high amount of phytoecdysteroids (PEs), which are widely used in traditional medicine in the Pacific islands. The PEs in two different Microsorum species, M. punctatum (MP) and M. scolopendria (MS), were examined using high-performance liquid chromatography (HPLC). In particular, MS produces a high amount of 20-hydroxyecdysone, which is the main active compound in PEs. To identify genes for PE biosynthesis, we generated reference transcriptomes from sterile frond tissues using the NovaSeq 6000 system. De novo transcriptome assembly after deleting contaminants resulted in 57,252 and 54,618 clean transcripts for MP and MS, respectively. The clean Microsorum transcripts for each species were annotated according to gene ontology terms, UniProt pathways, and the clusters of the orthologous group protein database using the MEGAN6 and Sma3s programs. In total, 1852 and 1980 transcription factors were identified for MP and MS, respectively. We obtained transcripts encoding for 38 and 32 enzymes for MP and MS, respectively, potentially involved in mevalonate and sterol biosynthetic pathways, which produce precursors for PE biosynthesis. Phylogenetic analyses revealed many redundant and unique enzymes between the two species. Overall, this study provides two Microsorum reference transcriptomes that might be useful for further studies regarding PE biosynthesis in Microsorum species.
Fine Mapping and Identification of BnaC06.FtsH1, a Lethal Gene That Regulates the PSII Repair Cycle in Brassica napus
Authors: Xu Kai , Wu Yujin , Song Jurong , Hu Kaining , Wu Zengxiang , Wen Jing , Yi Bin , Ma Chaozhi , Shen Jinxiong , Fu Tingdong , Tu Jinxing
Published: February 2021

Photosystem II (PSII) is an important component of the chloroplast. The PSII repair cycle is crucial for the relief of photoinhibition and may be advantageous when improving stress resistance and photosynthetic efficiency. Lethal genes are widely used in the efficiency detection and method improvement of gene editing. In the present study, we identified the naturally occurring lethal mutant 7-521Y with etiolated cotyledons in Brassica napus, controlled by double-recessive genes (named cyd1 and cyd2). By combining whole-genome resequencing and map-based cloning, CYD1 was fine-mapped to a 29 kb genomic region using 15,167 etiolated individuals. Through cosegregation analysis and functional verification of the transgene, BnaC06.FtsH1 was determined to be the target gene; it encodes an filamentation temperature sensitive protein H 1 (FtsH1) hydrolase that degrades damaged PSII D1 in Arabidopsis thaliana. The expression of BnaC06.FtsH1 was high in the cotyledons, leaves, and flowers of B. napus, and localized in the chloroplasts. In addition, the expression of EngA (upstream regulation gene of FtsH) increased and D1 decreased in 7-521Y. Double mutants of FtsH1 and FtsH5 were lethal in A. thaliana. Through phylogenetic analysis, the loss of FtsH5 was identified in Brassica, and the remaining FtsH1 was required for PSII repair cycle. CYD2 may be a homologous gene of FtsH1 on chromosome A07 of B. napus. Our study provides new insights into lethal mutants, the findings may help improve the efficiency of the PSII repair cycle and biomass accumulation in oilseed rape.
Autosomal Dominant Gyrate Atrophy-Like Choroidal Dystrophy Revisited: 45 Years Follow-Up and Association with a Novel C1QTNF5 Missense Variant
Authors: Kellner Ulrich , Weisschuh Nicole , Weinitz Silke , Farmand Ghazaleh , Deutsch Sebastian , Kortüm Friederike , Mazzola Pascale , Schäferhoff Karin , Marino Valerio , Dell’Orco Daniele
Published: February 2021

We present a long-term follow-up in autosomal dominant gyrate atrophy-like choroidal dystrophy (adGALCD) and propose a possible genotype/phenotype correlation. Ophthalmic examination of six patients from two families revealed confluent areas of choroidal atrophy resembling gyrate atrophy, starting in the second decade of life. Progression continued centrally, reaching the fovea at about 60 years of age. Subretinal deposits, retinal pigmentation or choroidal neovascularization as seen in late-onset retinal degeneration (LORD) were not observed. Whole genome sequencing revealed a novel missense variant in the C1QTNF5 gene (p.(Q180E)) which was found in heterozygous state in all affected subjects. Haplotype analysis showed that this variant found in both families is identical by descent. Three-dimensional modeling of the possible supramolecular assemblies of C1QTNF5 revealed that the p.(Q180E) variant led to the destabilization of protein tertiary and quaternary structures, affecting both the stability of the single protomer and the entire globular head, thus exerting detrimental effects on the formation of C1QTNF5 trimeric globular domains and their interaction. In conclusion, we propose that the p.(Q180E) variant causes a specific phenotype, adGALCD, that differs in multiple clinical aspects from LORD. Disruption of optimal cell-adhesion mechanisms is expected when analyzing the effects of the point mutation at the protein level.
Ablative Radiotherapy Reprograms the Tumor Microenvironment of a Pancreatic Tumor in Favoring the Immune Checkpoint Blockade Therapy
Authors: Lee Yu-Hung , Yu Ching-Fang , Yang Ying-Chieh , Hong Ji-Hong , Chiang Chi-Shiun
Published: February 2021

The low overall survival rate of patients with pancreatic cancer has driven research to seek a new therapeutic protocol. Radiotherapy (RT) is frequently an option in the neoadjuvant or palliative settings for pancreatic cancer treatment. This study explored the effect of RT protocols on the tumor microenvironment (TME) and their consequent impact on anti-programmed cell death ligand-1 (PD-L1) therapy. Using a murine orthotopic pancreatic tumor model, UN-KC-6141, RT-disturbed TME was examined by immunohistochemical staining. The results showed that ablative RT is more effective than fractionated RT at recruiting T cells. On the other hand, fractionated RT induces more myeloid-derived suppressor cell infiltration than ablative RT. The RT-disturbed TME presents a higher perfusion rate per vessel. The increase in vessel perfusion is associated with a higher amount of anti-PD-L1 antibody being delivered to the tumor. Animal survival is increased by anti-PD-L1 therapy after ablative RT, with 67% of treated animals surviving more than 30 days after tumor inoculation compared to a median survival time of 16.5 days for the control group. Splenocytes isolated from surviving animals were specifically cytotoxic for UN-KC-6141 cells. We conclude that the ablative RT-induced TME is more suited than conventional RT-induced TME to combination therapy with immune checkpoint blockade.
Monitoring People’s Emotions and Symptoms from Arabic Tweets during the COVID-19 Pandemic
Authors: Al-Laith Ali , Alenezi Mamdouh
Published: February 2021

Coronavirus-19 (COVID-19) started from Wuhan, China, in late December 2019. It swept most of the world’s countries with confirmed cases and deaths. The World Health Organization (WHO) declared the virus a pandemic on 11 March 2020 due to its widespread transmission. A public health crisis was declared in specific regions and nation-wide by governments all around the world. Citizens have gone through a wide range of emotions, such as fear of shortage of food, anger at the performance of governments and health authorities in facing the virus, sadness over the deaths of friends or relatives, etc. We present a monitoring system of citizens’ concerns using emotion detection in Twitter data. We also track public emotions and link these emotions with COVID-19 symptoms. We aim to show the effect of emotion monitoring on improving people’s daily health behavior and reduce the spread of negative emotions that affect the mental health of citizens. We collected and annotated 5.5 million tweets in the period from January to August 2020. A hybrid approach combined rule-based and neural network techniques to annotate the collected tweets. The rule-based technique was used to classify 300,000 tweets relying on Arabic emotion and COVID-19 symptom lexicons while the neural network was used to expand the sample tweets that were annotated using the rule-based technique. We used long short-term memory (LSTM) deep learning to classify all of the tweets into six emotion classes and two types (symptom and non-symptom tweets). The monitoring system shows that most of the tweets were posted in March 2020. The anger and fear emotions have the highest number of tweets and user interactions after the joy emotion. The results of user interaction monitoring show that people use likes and replies to interact with non-symptom tweets while they use re-tweets to propagate tweets that mention any of COVID-19 symptoms. Our study should help governments and decision-makers to dispel people’s fears and discover new symptoms associated with the symptoms that were declared by the WHO. It can also help in the understanding of people’s mental and emotional issues to address them before the impact of disease anxiety becomes harmful in itself.
A New Experimental Investigation for Improving Bridge Management Systems and Road Operation Sustainability
Authors: Giuffrè Tullio , Fossetti Marinella , Siciliano Alfio Francesco
Published: February 2021

Generally, during maintenance operations on bridges and motorway viaducts, the circulation of vehicles is limited or suspended. This causes significant economic losses due to the increase in the costs of transport: delays, increased fuel consumption, higher emissions of pollutants into the atmosphere, increased risk of accidents, etc. However, few studies have analyzed the influence of bridge vibrations on the final mechanical properties of the cement mortar placing during ordinary bridge service. As such, interest is increasing in repair techniques that could achieve high structural performance without reducing road service levels. This paper provides the results obtained through an innovative laboratory trials campaign that evaluated the influence of vibrations on the mechanical properties of high-performance mortar used for repairing bridge decks. The results of 24 cubic and prismatic specimens showed the relationship between the traffic-induced vibrations and the mechanical characteristics of the studied mortar. The findings can be considered as the first methodologic step that is necessary to address further field studies, drawing a detailed link between the repair techniques and transportation user costs. Based on the obtained results, a synthetic bridge management system framework was developed that merges the road function into the structural issue with the goals of increasing the resilience of road networks and optimizing the maintenance resources budget.
Unexpected Effects of Local Management and Landscape Composition on Predatory Mites and Their Food Resources in Vineyards
Authors: Möth Stefan , Walzer Andreas , Redl Markus , Petrović Božana , Hoffmann Christoph , Winter Silvia
Published: February 2021

Viticultural practices and landscape composition are the main drivers influencing biological pest control in vineyards. Predatory mites, mainly phytoseiid (Phytoseiidae) and tydeoid mites (Tydeidae), are important to control phytophagous mites (Tetranychidae and Eriophyidae) on vines. In the absence of arthropod prey, pollen is an important food source for predatory mites. In 32 paired vineyards located in Burgenland/Austria, we examined the effect of landscape composition, management type (organic/integrated), pesticide use, and cover crop diversity of the inter-row on the densities of phytoseiid, tydeoid, and phytophagous mites. In addition, we sampled pollen on vine leaves. Typhlodromus pyri Scheuten was the main phytoseiid mite species and Tydeus goetzi Schruft the main tydeoid species. Interestingly, the area-related acute pesticide toxicity loading was higher in organic than in integrated vineyards. The densities of phytoseiid and tydeoid mites was higher in integrated vineyards and in vineyards with spontaneous vegetation. Their population also profited from an increased viticultural area at the landscape scale. Eriophyoid mite densities were extremely low across all vineyards and spider mites were absent. Biological pest control of phytophagous mites benefits from less intensive pesticide use and spontaneous vegetation cover in vineyard inter-rows, which should be considered in agri-environmental schemes.
Acknowledgment to Reviewers of Journal of Clinical Medicine in 2020
Authors:   Journal of Clinical Medicine Editorial Office
Published: February 2021

Peer review is the driving force of journal development, and reviewers are gatekeepers who ensure that Journal of Clinical Medicine maintains its standards for the high quality of its published papers [...]
Associations of MDM2 and MDM4 Polymorphisms with Early-Stage Breast Cancer
Authors: Bartnykaitė Agnė , Savukaitytė Aistė , Ugenskienė Rasa , Daukšaitė Monika , Korobeinikova Erika , Gudaitienė Jurgita , Juozaitytė Elona
Published: February 2021

Breast cancer is one of the most common cancers worldwide. Single nucleotide polymorphisms (SNPs) in MDM2 and MDM4 have been associated with various cancers. However, the influence on clinical characteristics of breast cancer has not been sufficiently investigated yet. Thus, this study aimed to investigate the relationship between SNPs in MDM2 (rs2279744, rs937283, rs937282) and MDM4 (rs1380576, rs4245739) and I–II stage breast cancer. For analysis, the genomic DNA was extracted from 100 unrelated women peripheral blood. Polymorphisms were analyzed with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. The study showed that MDM2 rs937283 and rs937282 were significantly associated with estrogen receptor status and human epidermal growth factor receptor 2 (HER2) status. SNPs rs1380576 and rs4245739, located in MDM4, were significantly associated with status of estrogen and progesterone receptors. Our findings suggest that rs937283 AG, rs937282 CG, rs1380576 CC, and rs4245739 AA genotypes were linked to hormonal receptor positive breast cancer and may be useful genetic markers for disease assessment.
Aberrant Expression of TLR2, TLR7, TLR9, Splicing Variants of TLR4 and MYD88 in Chronic Lymphocytic Leukemia Patients
Authors: Skorka Katarzyna , Wlasiuk Paulina , Karczmarczyk Agnieszka , Giannopoulos Krzysztof
Published: February 2021

Functional toll-like receptors (TLRs) could modulate anti-tumor effects by activating inflammatory cytokines and the cytotoxic T-cells response. However, excessive TLR expression could promote tumor progression, since TLR-induced inflammation might stimulate cancer cells expansion into the microenvironment. Myd88 is involved in activation NF-κB through TLRs downstream signaling, hence in the current study we provided, for the first time, a complex characterization of expression of TLR2, TLR4, TLR7, TLR9, and MYD88 as well as their splicing forms in two distinct compartments of the microenvironment of chronic lymphocytic leukemia (CLL): peripheral blood and bone marrow. We found correlations between MYD88 and TLRs expressions in both compartments, indicating their relevant cooperation in CLL. The MYD88 expression was higher in CLL patients compared to healthy volunteers (HVs) (0.1780 vs. 0.128, p < 0.0001). The TLRs expression was aberrant in CLL compared to HVs. Analysis of survival curves revealed a shorter time to first treatment in the group of patients with low level of TLR4(3) expression compared to high level of TLR4(3) expression in bone marrow (13 months vs. 48 months, p = 0.0207). We suggest that TLRs expression is differentially regulated in CLL but is similarly shared between two distinct compartments of the microenvironment.
Level III Reliability Design of an Armor Block of Rubble Mound Breakwater Using Probabilistic Model of Wave Height Optimized for the Korean Sea Wave Conditions and Non-Gaussian Wave Slope Distribution
Authors: Cho Yong Jun
Published: February 2021

In this study, a Level III reliability design of an armor block of rubble mound breakwater was developed using the optimized probabilistic wave height model for the Korean marine environment and Van der Meer equation. To demonstrate what distinguishes this study from the others, numerical simulation was first carried out, assuming that wave slope follows Gaussian distribution recommended by PIANC. Numerical results showed that Gaussian wave slope distribution overpredicted the failure probability of armor block, longer and shorter waves, and on the contrary, underpredicted waves of the medium period. After noting the limitations of Gaussian distribution, some efforts were made to develop an alternative for Gaussian distribution. As a result, non-Gaussian wave slope distribution was analytically derived from the joint distribution of wave amplitude and period by Longuet–Higgins using the random variables transformation technique. Numerical results showed that non-Gaussian distribution could effectively address the limitations of Gaussian distribution due to its capability to account for the nonlinear resonant wave–wave interaction and its effects on the wave slope distribution that significantly influences the armor block’s stability. Therefore, the non-Gaussian wave slope distribution presented in this study could play an indispensable role in addressing controversial issues such as whether or not enormous armor blocks like a Tetrapod of 100 t frequently mentioned in developing countermeasures against rough seas due to climate change is too conservatively designed.
A Coupled Macroscopic and Mesoscopic Creep Model of Soft Marine Soil Using a Directional Probability Entropy Approach
Authors: Zhou Cuiying , Cui Guangjun , Liang Wanyi , Liu Zhen , Zhang Lihai
Published: February 2021

To mitigate the risk of structural failure in coastal engineering caused by soft marine soil creep, this study presents a coupled macroscopic and mesoscopic creep model of soft marine soil to predict long-term deformation behavior of the soil. First, the mesoscopic characteristics of soft marine soil (e.g., pore, particle, and morphological characteristics) under different external pressures were obtained using a scanning electron microscope. Then, both the mesoscopic and macroscopic characteristics of soil were quantified using directional probability entropy and then used as inputs to develop the model. The model predictions agree with the experimental data. In addition, the experimental results indicate linear negative correlations between porosity and pore ratio with stress—the relationships between the fractal dimension of pore distribution and probability entropy of particle orientation under stress are generally nonlinear. Further, results of sensitivity analysis indicate that the probability entropy of particle orientation is one of the most critical parameters governing long-term creep deformation behavior of soft marine soil.
Underwater Image Enhancement Based on Local Contrast Correction and Multi-Scale Fusion
Authors: Gao Farong , Wang Kai , Yang Zhangyi , Wang Yejian , Zhang Qizhong
Published: February 2021

In this study, an underwater image enhancement method based on local contrast correction (LCC) and multi-scale fusion is proposed to resolve low contrast and color distortion of underwater images. First, the original image is compensated using the red channel, and the compensated image is processed with a white balance. Second, LCC and image sharpening are carried out to generate two different image versions. Finally, the local contrast corrected images are fused with sharpened images by the multi-scale fusion method. The results show that the proposed method can be applied to water degradation images in different environments without resorting to an image formation model. It can effectively solve color distortion, low contrast, and unobvious details of underwater images.
Examining the Impact of Financial Development on Energy Production in Emerging Economies
Authors: Wilmot Neil A. , Taivan Ariuna
Published: February 2021

Global energy production has been on the rise for many years, and reliance on traditional sources of energy remains strong. The extraction and production of energy can serve as an important avenue of growth, particularly for developing economies. To undertake such capital intensive project requires significant investment, and, intuitively, a well-functioning domestic financial system would be expected to aid in the growth of such industries. We investigate the relationship between financial development and energy production for 15 emerging countries, over the period of 1995–2017. After establishing the presence of a unit root, based upon panel data methods, a cointegrating relationship between financial development and energy production is confirmed. The results of the fully modified ordinary least squares (FMOLS) estimation establish a long run relationship in 11 of 15 countries in the sample. Panel Granger causality results provide a link between energy production and foreign direct investment (FDI), while such a link is absent for domestic credit. Policymakers should understand that development of the energy sector can provide an incentive for foreign firms to invest in emerging economics.
Key Disaster-Causing Factors Chains on Urban Flood Risk Based on Bayesian Network
Authors: Huang Shanqing , Wang Huimin , Xu Yejun , She Jingwen , Huang Jing
Published: February 2021

Drivers of urban flood disaster risk may be related to many factors from nature and society. However, it is unclear how these factors affect each other and how they ultimately affect the risk. From the perspective of risk uncertainty, flood inundation risk is considered to be the probability of inundation consequences under the influence of various factors. In this paper, urban flood inundation risk assessment model is established based on Bayesian network, and then key disaster-causing factors chains are explored through influence strength analysis. Jingdezhen City is selected as study area, where the flood inundation probability is calculated, and the paths of these influential factors are found. The results show that the probability of inundation in most areas is low. Risk greater than 0.8 account for about 9%, and most of these areas are located in the middle and southern section of the city. The influencing factors interact with each other in the form of factor chain and, finally, affect the flood inundation. Rainfall directly affects inundation, while river is the key factor on inundation which is influenced by elevation and slope. In addition, in the chain of socio-economic factors, the population will determine the pipe density through affecting gross domestic product (GDP), and lead to the inundation. The approach proposed in this study can be used to find key disaster-causing factors chains, which not only quantitatively reveal the formation of risks but also provide reference for early warning.
Mechanisms of Cisplatin in Combination with Repurposed Drugs against Human Endometrial Carcinoma Cells
Authors: Lin Chi-Kang , Liu Shu-Ting , Wu Zih-Syuan , Wang Yu-Chi , Huang Shih-Ming
Published: February 2021

Although endometrial carcinoma is one of the most common gynecological malignancies worldwide, its precise etiology remains unknown. Moreover, no novel adjuvant and/or targeted therapies are currently being developed to achieve greater efficacy for endometrial cancer patients who develop chemotherapeutic drug resistance. In this study, we used three human endometrial cancer cell lines, RL95-2, HEC-1-A, and KLE, to investigate the responsiveness of cisplatin alone and in combination with potential repurposed drugs. We first found that RL95-2 cells were more sensitive to cisplatin than HEC-1-A or KLE cells. The cytotoxicity of cisplatin in RL95-2 cells may reflect its ability to perturb the cell cycle, reactive oxygen species production and autophagy as well as to induce senescence and DNA damage. Similar effects, although not DNA damage, were also observed in HEC-1-A and KLE cells. In addition, downregulation of p53 and/or cyclin D1 may also impact the responsiveness of HEC-1-A and KLE cells to cisplatin. We also observed that resveratrol, trichostatin A (TSA), caffeine, or digoxin increased the apoptotic process of cisplatin toward RL95-2 cells, while amiodarone or TSA increased its apoptotic process toward HEC-1-A cells. The combination index supported the assertion that the combination of cisplatin with caffeine, amiodarone, resveratrol, metformin, digoxin, or TSA increases the cytotoxicity of cisplatin in HEC-1-A cells. These findings suggest potential strategies for enhancing the efficacy of cisplatin to overcome drug resistance in endometrial carcinoma patients.
The Possible Detriment of Oxygen in Creep of Alumina and Zirconia Ceramic Composites Reinforced with Graphene
Authors: Cano-Crespo Rafael , Rivero-Antúnez Pedro , Gómez-García Diego , Moreno Rodrigo , Domínguez-Rodríguez Arturo
Published: February 2021

This paper is aims to give an answer to the following question: is the oxidation of graphene a critical issue for high-temperature plasticity in graphene-reinforced ceramics? To give a convincing reply, we will focus on two very different graphene-based ceramic composites: reduced graphene oxide (rGO)-reinforced alumina (α-Al2O3) and reduced graphene oxide (rGO)-reinforced yttria tetragonal zirconia (t-ZrO2). The processing of the powders has been made using a colloidal route, and after that, a spark plasma sintering process was performed in order to densify the samples. Creep tests were performed at temperatures between 1200–1250 °C in an argon atmosphere. The microstructure obtained by an SEM of the sintered and tested specimens was characterized quantitatively to elucidate the deformation mechanism. Raman spectroscopy was carried out to check the integrity of the graphene. The average grain size was in the order of 1 µm and the shape factor was 0.7 for all the studied materials. The integrity of the graphene was checked before and after the creep experiments. The careful analysis of the creep tests shows that graphene oxide or its reduced version are not efficient phases for creep resistance improvement in general, contrary to what is reported elsewhere. However, the results permit the suggestion of a creep improvement in nanocomposites at a very high temperature regime due to an enhanced reactivity of oxygen between carbon and alumina interfaces. In the case of zirconia, the results give us the conclusion that the oxidation of graphene is a highly detrimental issue regarding the improvement of high-temperature plasticity.
Study on the Superhydrophobic Properties of an Epoxy Resin-Hydrogenated Silicone Oil Bulk Material Prepared by Sol-Gel Methods
Authors: Zheng Kui , Zhu Jie , Liu Haifeng , Zhang Xingquan , Wang Enze
Published: February 2021

A superhydrophobic material was prepared by a simple and easily accessed sol-gel method using epoxy resin (E-51) and γ-aminopropyltriethoxysilane (KH-550) as the precursors, aqueous ammonia (NH4OH) as the catalyst and hydrogenated silicone oil (PMHS) as the hydrophobic modifier, and then pelleting the final product. The morphologies, surface chemical properties and thermal stability of the superhydrophobic bulk materials were characterized by scanning electron microscopy, Fourier infrared spectrometry and thermal analyzer. The hydrophobic properties and repairability of the as-prepared materials were also studied. The results showed that the prepared epoxy resin-hydrogenated silicone oil bulk materials were composed of tightly bound nanoparticles with a size of 50–100 nm in diameter. The material showed excellent superhydrophobic properties with a surface contact angle of 152°. The material also had good thermal resistance with a heat-resistant temperature of 300 °C and showed good repairability. The epoxy resin-hydrogenated silicone oil bulk superhydrophobic material exhibited excellent performance and showed wide application prospects.