bluuebunny/crossref_metadata_2025 huggingface dataset:
The Cognition of Audience to Artistic Style Transfer
Authors: Lyu Yanru , Lin Chih-Long , Lin Po-Hsien , Lin Rungtai
Published: April 2021

Artificial Intelligence (AI) is becoming more popular in various fields, including the area of art creation. Advances in AI technology bring new opportunities and challenges in the creation, experience, and appreciation of art. The neural style transfer (NST) realizes the intelligent conversion of any artistic style using neural networks. However, the artistic style is the product of cognition that involving from visual to feel. The purpose of this paper is to study factors affecting audience cognitive difference and preference on artistic style transfer. Those factors are discussed to investigate the application of the AI generator model in art creation. Therefore, based on the artist’s encoding attributes (color, stroke, texture) and the audience’s decoding cognitive levels (technical, semantic, effectiveness), this study proposed a framework to evaluate artistic style transfer in the perspective of cognition. Thirty-one subjects with a background in art, aesthetics, and design were recruited to participate in the experiment. The experimental process consists of four style groups, including Fauvism, Expressionism, Cubism, and Renaissance. According to the finding in this study, participants can still recognize different artistic styles after transferred by neural networks. Besides, the features of texture and stroke are more impact on the perception of fitness than color. The audience may prefer the samples with high cognition in the semantic and effectiveness levels. The above indicates that through AI automated routine work, the cognition of the audience to artistic style still can be kept and transferred.
Bioactive Properties of Breads Made with Sourdough of Hull-Less Barley or Conventional and Pigmented Wheat Flours
Authors: Luti Simone , Galli Viola , Venturi Manuel , Granchi Lisa , Paoli Paolo , Pazzagli Luigia
Published: April 2021

Functional and nutritional properties of baked goods can be enhanced by the use of sourdough fermentation, which is defined as a mixture of water and flour fermented by lactobacilli (LAB) and yeasts. Previous data highlighted the ability of sourdoughs obtained with selected LAB strains and commercial flour to produce bioactive peptides equipped with antioxidant and anti-inflammatory properties. More recently, it has been proven that choosing the most suitable combination of selected LAB and high-functional-value flours greatly increase the amount of low-molecular-weight antioxidant compounds responsible for improving the nutritional value of the products. This work aimed to isolate bioactive peptides both from sourdoughs and baked breads obtained with pigmented wheat and barley and a selected combination of LABs. Soluble water extracts were obtained, and low-molecular-weight peptides were isolated. Antioxidant activity was detected by assaying the intracellular ROS production in stressed cultured macrophages, treated with peptides. Moreover, anti-inflammatory activity, highlighted by NFkB pathway inhibition and by COX2 reduction in stressed cells, was demonstrated for peptides obtained from breads. The results allowed the conclusion that the combination of flours and LAB used in the present manuscript led to the production of bakery products with beneficial effects on oxidative and inflammatory status.
CYP2C19 Polymorphisms in Indonesia: Comparison among Ethnicities and the Association with Clinical Outcomes
Authors: Miftahussurur Muhammad , Doohan Dalla , Syam Ari Fahrial , Nusi Iswan Abbas , Subsomwong Phawinee , Waskito Langgeng Agung , Maulahela Hasan , Akil Fardah , Uwan Willy Brodus , Siregar Gontar , Fauzia Kartika Afrida , Rezkitha Yudith Annisa Ayu , Rahman Abdul , Wibawa I Dewa Nyoman , Saudale Alexander Michael Joseph , Richardo Marselino , Sugihartono Titong , Chomariyati Alvi , Bramantoro Taufan , Uchida Tomohisa , Yamaoka Yoshio
Published: April 2021

CYP2C19 polymorphisms are important factors for proton pump inhibitor-based therapy. We examined the CYP2C19 genotypes and analyzed the distribution among ethnicities and clinical outcomes in Indonesia. We employed the polymerase chain reaction-restriction fragment length polymorphism method to determine the CYP2C19 genotypes and evaluated inflammation severity with the updated Sydney system. For CYP2C19*2, 46.4% were the homozygous wild-type allele, 14.5% were the homozygous mutated allele, and 39.2% were the heterozygous allele. For CYP2C19*3, 88.6% were the homozygous wild-type allele, 2.4% were the homozygous mutated allele, and 9.0% were the heterozygous allele. Overall, the prevalence of rapid, intermediate, and poor metabolizers in Indonesia was 38.5, 41.6, and 19.9%, respectively. In the poor metabolizer group, the frequency of allele *2 (78.8%) was higher than the frequency of allele *3 (21.2%). The Papuan had a significantly higher likelihood of possessing poor metabolizers than the Balinese (OR 11.0; P = 0.002). The prevalence of poor metabolizers was lower compared with the rapid and intermediate metabolizers among patients with gastritis and gastroesophageal reflux disease. Intermediate metabolizers had the highest prevalence, followed by rapid metabolizers and poor metabolizers. Dosage adjustment should therefore be considered when administering proton pump inhibitor-based therapy in Indonesia.
Diversion Colitis: Macro and Microscopic Findings after Probiotics Stimulation
Authors: Rodríguez-Padilla Ángela , Morales-Martín Germán , Pérez-Quintero Rocío , Gómez-Salgado Juan , Rada-Morgades Ricardo , Ruiz-Frutos Carlos
Published: April 2021

The use of a loop ileostomy as the defunctioning procedure of choice to protect a distal colonic anastomosis causes histological and endoscopic changes in the intestinal mucosal architecture, which have been related to chronic inflammation and changes in the microflora that consequently impact the intestinal structure and function following fecal stream diversion. The aim of this study was to evaluate the histological and endoscopic changes on the colonic mucosa in patients with diversion colitis after stimulation of the efferent loop with probiotics prior to closure of the protective ileostomy. A prospective, randomized, double-blind, controlled study was designed. All patients who underwent surgery for colorectal carcinoma with protective ileostomy between January 2017 and December 2018 were included. These patients were pending reconstructive surgery and were diagnosed with endoscopic and histological diversion colitis. Divided into two groups, a group stimulated with probiotics (SG) and a control group (CG). 34 cases and 35 controls were included in the study. Histological and endoscopic changes were evaluated after stimulation, after restorative surgery and during the short-term follow-up after surgery. A decrease in endoscopic pathological findings (mucosal friability, mucous erosions, polyps, edema, erythema and stenosis) and in histological findings (follicular hyperplasia, eosinophils, cryptic abscesses, lymphocyte infiltration, plasma cell infiltration and architecture distortion) was observed in SG. These results were statistically significant with a p < 0.001. The stimulation of the efferent loop of the ileostomy in patients with diversion colitis produced a decrease of the endoscopic and histological severity of colitis in the short term.
Virtual Environment Rehabilitation for Patients with Motor Neglect Trial (VERMONT): A Single-Center Randomized Controlled Feasibility Trial
Authors: de Villiers Elsje , Stone Thomas , Wang Nai-Wei , Sarangi Viswadeep , Pelah Adar , Shenker Nicholas
Published: April 2021

Background: Motor neglect occurs in patients with chronic pain conditions. Virtual environments (VE) help rehabilitation through biofeedback and improving motivation. Aim: To assess the feasibility of a VE for patients with motor neglect with chronic pain. Methods: 10 subjects with chronic pain (Fibromyalgia, Sciatica, and Complex Regional Pain Syndrome) underwent a treadmill task three times per week for two weeks. Groups were randomized to receive real-time biofeedback from the VE (intervention) or shown still images (control). Primary outcomes were: (i) distance walked at baseline compared to the final 5 min cycle of week 2; (ii) the Lower Extremity Functional Index (LEFI) questionnaire. A satisfaction questionnaire was used. Follow up was to 24 weeks. Results: Total distance walked was significantly higher in the intervention group (p < 0.05), and 33% (2/6) of the intervention group had a clinically important LEFI improvement compared to 0/4 in the control group at week 2. No secondary outcome measures demonstrated any significant differences. The intervention received high satisfaction scores, significantly greater than the control group at week 24. No harms were recorded. Discussion: This feasibility study showed that VE and treadmill-walking improved walking distances and function for subjects with motor neglect. This is a promising novel approach and requires further validation through larger study.
Small Cell Lung Cancer: State of the Art of the Molecular and Genetic Landscape and Novel Perspective
Authors: Denninghoff Valeria , Russo Alessandro , de Miguel-Pérez Diego , Malapelle Umberto , Benyounes Amin , Gittens Allison , Cardona Andres Felipe , Rolfo Christian
Published: April 2021

Small cell lung cancer (SCLC) is a highly proliferative lung cancer that is not amenable to surgery in most cases due to the high metastatic potential. Precision medicine has not yet improved patients’ survival due to the lack of actionable mutations. Intra- and intertumoral heterogeneity allow the neoplasms to adapt to various microenvironments and treatments. Further studying this heterogeneous cancer might yield the discovery of actionable mutations. First-line SCLC treatment has added immunotherapy to its armamentarium. There has been renewed interest in SCLC, and numerous clinical trials are underway with novel therapeutic approaches. Understanding the molecular and genetic landscape of this heterogeneous and lethal disease will pave the way for novel drug development.
Succinate Anaplerosis Has an Onco-Driving Potential in Prostate Cancer Cells
Authors: Sant’Anna-Silva Ana Carolina B. , Perez-Valencia Juan A. , Sciacovelli Marco , Lalou Claude , Sarlak Saharnaz , Tronci Laura , Nikitopoulou Efterpi , Meszaros Andras T. , Frezza Christian , Rossignol Rodrigue , Gnaiger Erich , Klocker Helmut
Published: April 2021

Tumor cells display metabolic alterations when compared to non-transformed cells. These characteristics are crucial for tumor development, maintenance and survival providing energy supplies and molecular precursors. Anaplerosis is the property of replenishing the TCA cycle, the hub of carbon metabolism, participating in the biosynthesis of precursors for building blocks or signaling molecules. In advanced prostate cancer, an upshift of succinate-driven oxidative phosphorylation via mitochondrial Complex II was reported. Here, using untargeted metabolomics, we found succinate accumulation mainly in malignant cells and an anaplerotic effect contributing to biosynthesis, amino acid, and carbon metabolism. Succinate also stimulated oxygen consumption. Malignant prostate cells displayed higher mitochondrial affinity for succinate when compared to non-malignant prostate cells and the succinate-driven accumulation of metabolites induced expression of mitochondrial complex subunits and their activities. Moreover, extracellular succinate stimulated migration, invasion, and colony formation. Several enzymes linked to accumulated metabolites in the malignant cells were found upregulated in tumor tissue datasets, particularly NME1 and SHMT2 mRNA expression. High expression of the two genes was associated with shorter disease-free survival in prostate cancer cohorts. Moreover, in-vitro expression of both genes was enhanced in prostate cancer cells upon succinate stimulation. In conclusion, the data indicate that uptake of succinate from the tumor environment has an anaplerotic effect that enhances the malignant potential of prostate cancer cells.
Predictive Factors for RAI-Refractory Disease and Short Overall Survival in PDTC
Authors: Kersting David , Seifert Robert , Kessler Lukas , Herrmann Ken , Theurer Sarah , Brandenburg Tim , Dralle Henning , Weber Frank , Umutlu Lale , Führer-Sakel Dagmar , Görges Rainer , Rischpler Christoph , Weber Manuel
Published: April 2021

Background: The clinical phenotype of poorly differentiated thyroid cancer (PDTC) can vary substantially. We aim to evaluate risk factors for radioiodine refractory (RAI-R) disease and reduced overall survival (OS). Methods: We retrospectively screened our institutional database for PDTC patients. For the assessment of RAI-R disease, we included patients who underwent dual imaging with 18F-FDG-PET and 124I-PET/131I scintigraphy that met the internal standard of care. We tested primary size, extrathyroidal extension (ETE), and age >55 years as risk factors for RAI-R disease at initial diagnosis and during the disease course using uni- and multivariate analyses. We tested metabolic tumor volume (MTV), total lesion glycolysis (TLG) on 18F-FDG-PET, and the progression of stimulated thyroglobulin within 4–6 months of initial radioiodine therapy as prognostic markers for OS. Results: Size of primary >40 mm and ETE were significant predictors of RAI-R disease in the course of disease in univariate (81% vs. 27%, p = 0.001; 89% vs. 33%, p < 0.001) and multivariate analyses. Primary tumor size was an excellent predictor of RAI-R disease (AUC = 0.90). TLG/MTV > upper quartile and early thyroglobulin progression were significantly associated with shorter median OS (29.0 months vs. 56.9 months, p < 0.05; 57.8 months vs. not reached p < 0.005, respectively). Discussion: PDTC patients, especially those with additional risk factors, should be assessed for RAI-R disease at initial diagnosis and in the course of disease, allowing for early implementation of multimodal treatment. Primary tumor size >40 mm, ETE, and age >55 are significant risk factors for RAI-R disease. High MTV/TLG is a significant risk factor for premature death and can help identify patients requiring intervention.
Tertiary Prevention of HCC in Chronic Hepatitis B or C Infected Patients
Authors: Teng Wei , Liu Yen-Chun , Jeng Wen-Juei , Su Chien-Wei
Published: April 2021

Hepatocellular carcinoma (HCC) ranks as a leading cause of common cancer and cancer-related death. The major etiology of HCC is due to chronic hepatitis virus including HBV and HCV infections. Scheduled HCC surveillance in high risk populations improves the early detection rate and the feasibility of curative treatment. However, high HCC recurrence rate still accounts for the poor prognosis of HCC patients. In this article, we critically review the pathogenesis of viral hepatitis-related hepatocellular carcinoma and the evidence of tertiary prevention efficacy by current available antiviral treatment, and discuss the knowledge gap in viral hepatitis-related HCC tertiary prevention.
Identification and Validation of an Immune-Associated RNA-Binding Proteins Signature to Predict Clinical Outcomes and Therapeutic Responses in Glioma Patients
Authors: Tian Ruotong , Li Yimin , Liu Qian , Shu Minfeng
Published: April 2021

The prognosis of patients with glioma is largely related to both the tumor-infiltrating immune cells and the expression of RNA-binding proteins (RBPs) that are able to regulate various pro-inflammatory and oncogenic mediators. However, immune-associated RBPs in glioma remain unexplored. In this study, we captured patient data from The Cancer Genome Atlas (TCGA) and divided them into two immune subtype groups according to the difference in infiltration of immune cells. After differential expression and co-expression analysis, we identified 216 RBPs defined as immune-associated RBPs. After narrowing down processes, eight RBPs were selected out to construct a risk signature that proven to be a novel and independent prognostic factor. The patients were divided into high- and low-risk groups on the basis of risk score. Higher risk scores meant worse overall survival and higher expression of human leukocyte antigen and immune checkpoints such as PD1 and CTLA4. In addition, analyses of pathway enrichment, somatic mutation, copy number variations and immuno-/chemotherapeutic response prediction were performed in high- and low-risk groups and compared with each other. For the first time, we demonstrated a novel signature composed of eight immune-associated RBPs that was valuable in predicting the survival of glioma patients and directing immunotherapy and chemotherapy.
Matched-Pair Analysis of Survival in the Patients with Advanced Laryngeal and Hypopharyngeal Squamous Cell Carcinoma Treated with Induction Chemotherapy Plus Chemo-Radiation or Total Laryngectomy
Authors: García-Cabo Patricia , López Fernando , Sánchez-Canteli Mario , Fernández-Vañes Laura , Álvarez-Marcos César , Llorente José Luis , Rúa Maria Ángeles de la , Blay Pilar , Rodrigo Juan P.
Published: April 2021

Background: We performed a comparative analysis between an organ-preservation protocol and surgery followed by radiotherapy in patients with locally advanced squamous cell carcinoma of the larynx and hypopharynx; Methods: 60 previously untreated patients who were treated with induction chemotherapy followed by chemoradiotherapy in responders were compared with a control group of 60 patients treated with up-front surgery. Both groups were statistically comparable, according to the subsite, TNM (tumor-node-metastasis) stage, age, and sex; Results: Mean age was 58 years and 92% were male. No significant statistical difference was observed for overall survival (OS) (HR 0.75; 95% CI 0.48–1.18; P = 0.22) and disease-specific survival (DSS) (HR 0.98; 95% CI 0.52–1.83, P = 0.96). Also, there was no significant difference for recurrence-free survival (HR 0.931; 95% CI 0.57–1.71; P = 0.81), metastases-free survival (HR 2.23; 95% CI 0.67–7.41; P = 0.19), and the appearance of second primary tumors (HR 1.22; 95% CI 0.51–2.88; P = 0.64); Conclusions: The results of the organ-preservation approach did not appear inferior to those of surgery plus (chemo)radiotherapy for patients with T3/T4a larynx and T2–T4a hypopharynx cancer with respect to OS and DSS, locoregional control and metastases-free survival.
Plasma-Treated Solutions (PTS) in Cancer Therapy
Authors: Tanaka Hiromasa , Bekeschus Sander , Yan Dayun , Hori Masaru , Keidar Michael , Laroussi Mounir
Published: April 2021

Cold physical plasma is a partially ionized gas generating various reactive oxygen and nitrogen species (ROS/RNS) simultaneously. ROS/RNS have therapeutic effects when applied to cells and tissues either directly from the plasma or via exposure to solutions that have been treated beforehand using plasma processes. This review addresses the challenges and opportunities of plasma-treated solutions (PTSs) for cancer treatment. These PTSs include plasma-treated cell culture media in experimental research as well as clinically approved solutions such as saline and Ringer’s lactate, which, in principle, already qualify for testing in therapeutic settings. Several types of cancers were found to succumb to the toxic action of PTSs, suggesting a broad mechanism of action based on the tumor-toxic activity of ROS/RNS stored in these solutions. Moreover, it is indicated that the PTS has immuno-stimulatory properties. Two different routes of application are currently envisaged in the clinical setting. One is direct injection into the bulk tumor, and the other is lavage in patients suffering from peritoneal carcinomatosis adjuvant to standard chemotherapy. While many promising results have been achieved so far, several obstacles, such as the standardized generation of large volumes of sterile PTS, remain to be addressed.
Blockade of AMPK-Mediated cAMP–PKA–CREB/ATF1 Signaling Synergizes with Aspirin to Inhibit Hepatocellular Carcinoma
Authors: Zhang Hongying , Yang Songpeng , Wang Jiao , Jiang Yangfu
Published: April 2021

Aspirin can prevent or inhibit inflammation-related cancers, such as colorectal cancer and hepatocellular carcinoma (HCC). However, the effectiveness of chemotherapy may be compromised by activating oncogenic pathways in cancer cells. Elucidation of such chemoresistance mechanisms is crucial to developing novel strategies to maximize the anti-cancer effects of aspirin. Here, we report that aspirin markedly induces CREB/ATF1 phosphorylation in HCC cells, which compromises aspirin’s anti-HCC effect. Inhibition of AMP-activated protein kinase (AMPK) abrogates the induction of CREB/ATF1 phosphorylation by aspirin. Mechanistically, activation of AMPK by aspirin results in decreased expression of the urea cycle enzyme carbamoyl-phosphate synthase 1 (CPS1) in HCC cells and xenografts. Treatment with aspirin or CPS1 knockdown stimulates soluble adenylyl cyclase expression, thereby increasing cyclic AMP (cAMP) synthesis and stimulating PKA–CREB/ATF1 signaling. Importantly, abrogation of aspirin-induced CREB/ATF1 phosphorylation could sensitize HCC to aspirin. The bis-benzylisoquinoline alkaloid berbamine suppresses the expression of cancerous inhibitor of protein phosphatase 2A (CIP2A), leading to protein phosphatase 2A-mediated downregulation of CREB/ATF1 phosphorylation. The combination of berbamine and aspirin significantly inhibits HCC in vitro and in vivo. These data demonstrate that the regulation of cAMP-PKA-CREB/ATF1 signaling represents a noncanonical function of CPS1. Targeting the PKA–CREB/ATF1 axis may be a strategy to improve the therapeutic effects of aspirin on HCC.
Effects of Epstein-Barr Virus Infection on the Risk and Prognosis of Primary Laryngeal Squamous Cell Carcinoma: A Hospital-Based Case-Control Study in Taiwan
Authors: Lee Li-Ang , Fang Tuan-Jen , Li Hsueh-Yu , Chuang Hai-Hua , Kang Chung-Jan , Chang Kai-Ping , Liao Chun-Ta , Chen Tse-Ching , Huang Chung-Guei , Yen Tzu-Chen
Published: April 2021

Mounting molecular evidence supports Epstein–Barr virus (EBV) involvement in the pathogenesis of laryngeal squamous cell carcinoma (LSCC); however, the epidemiological data are inconsistent. In this retrospective case-control study, we aimed to determine whether EBV infection underlies the risk and prognosis of LSCC. The prevalence of EBV infection, as analyzed using an EBV DNA polymerase chain reaction assay, was significantly higher in 42 Taiwanese patients with newly diagnosed primary LSCC, compared to 39 age- and sex-matched control patients without cancer (48% vs. 19%). Furthermore, most of the EBER signals detected using in situ hybridization were localized to the nuclei of tumor-infiltrating lymphocytes. In multivariate analysis, EBV DNA positivity, age ≥ 55 years, cigarette smoking, and high BCL-2, B2M, and CD161 expression (assessed using immunohistochemistry) were identified as independent risk factors for LSCC. Furthermore, five-year local recurrence and disease-free survival rates were 34% and 58%, respectively, with a high EBER signal and low CD3 expression independently predicting five-year local recurrence and disease-free survival. Our comprehensive profiling data accurately identified patients at risk for LSCC development, local recurrence, or disease-free survival. The information obtained in this study improves our understanding of EBV infection in LSCC, and may guide precision medicine for patients with LSCC.
Combined Effects of Myeloid Cells in the Neuroblastoma Tumor Microenvironment
Authors: Frosch Jennifer , Leontari Ilia , Anderson John
Published: April 2021

Despite multimodal treatment, survival chances for high-risk neuroblastoma patients remain poor. Immunotherapeutic approaches focusing on the activation and/or modification of host immunity for eliminating tumor cells, such as chimeric antigen receptor (CAR) T cells, are currently in development, however clinical trials have failed to reproduce the preclinical results. The tumor microenvironment is emerging as a major contributor to immune suppression and tumor evasion in solid cancers and thus has to be overcome for therapies relying on a functional immune response. Among the cellular components of the neuroblastoma tumor microenvironment, suppressive myeloid cells have been described as key players in inhibition of antitumor immune responses and have been shown to positively correlate with more aggressive disease, resistance to treatments, and overall poor prognosis. This review article summarizes how neuroblastoma-driven inflammation induces suppressive myeloid cells in the tumor microenvironment and how they in turn sustain the tumor niche through suppressor functions, such as nutrient depletion and generation of oxidative stress. Numerous preclinical studies have suggested a range of drug and cellular therapy approaches to overcome myeloid-derived suppression in neuroblastoma that warrant evaluation in future clinical studies.
Epigenetics in a Spectrum of Myeloid Diseases and Its Exploitation for Therapy
Authors: Maher Michael , Diesch Jeannine , Le Pannérer Marguerite-Marie , Buschbeck Marcus
Published: April 2021

Mutations in genes encoding chromatin regulators are early events contributing to developing asymptomatic clonal hematopoiesis of indeterminate potential and its frequent progression to myeloid diseases with increasing severity. We focus on the subset of myeloid diseases encompassing myelodysplastic syndromes and their transformation to secondary acute myeloid leukemia. We introduce the major concepts of chromatin regulation that provide the basis of epigenetic regulation. In greater detail, we discuss those chromatin regulators that are frequently mutated in myelodysplastic syndromes. We discuss their role in the epigenetic regulation of normal hematopoiesis and the consequence of their mutation. Finally, we provide an update on the drugs interfering with chromatin regulation approved or in development for myelodysplastic syndromes and acute myeloid leukemia.
SIPA1 Is a Modulator of HGF/MET Induced Tumour Metastasis via the Regulation of Tight Junction-Based Cell to Cell Barrier Function
Authors: Liu Chang , Jiang Wenguo , Zhang Lijian , Hargest Rachel , Martin Tracey A.
Published: April 2021

Background: Lung cancer is the leading cause of cancer death. SIPA1 is a mitogen induced GTPase activating protein (GAP) and may hamper cell cycle progression. SIPA1 has been shown to be involved in MET signaling and may contribute to tight junction (TJ) function and cancer metastasis. Methods: Human lung tumour cohorts were analyzed. In vitro cell function assays were performed after knock down of SIPA1 in lung cancer cells with/without treatment. Quantitative polymerase chain reaction (qPCR) and western blotting were performed to analyze expression of HGF (hepatocyte growth factor), MET, and their downstream markers. Immunohistochemistry (IHC) and immunofluorescence (IFC) staining were performed. Results: Higher expression of SIPA1 in lung tumours was associated with a poorer prognosis. Knockdown of SIPA1 decreased invasiveness and proliferation of in vitro cell lines, and the SIPA1 knockdown cells demonstrated leaky barriers. Knockdown of SIPA1 decreased tight junction-based barrier function by downregulating MET at the protein but not the transcript level, through silencing of Grb2, SOCS, and PKCμ (Protein kinase Cµ), reducing the internalization and recycling of MET. Elevated levels of SIPA1 protein are correlated with receptor tyrosine kinases (RTKs), especially HGF/MET and TJs. The regulation of HGF on barrier function and invasion required the presence of SIPA1. Conclusions: SIPA1 plays an essential role in lung tumourigenesis and metastasis. SIPA1 may be a diagnostic and prognostic predictive biomarker. SIPA1 may also be a potential therapeutic target for non-small cell lung cancer (NSCLC) patients with aberrant MET expression and drug resistance.
Primary Human Cardiomyocytes and Cardiofibroblasts Treated with Sera from Myocarditis Patients Exhibit an Increased Iron Demand and Complex Changes in the Gene Expression
Authors: Kobak Kamil A. , Franczuk Paweł , Schubert Justyna , Dzięgała Magdalena , Kasztura Monika , Tkaczyszyn Michał , Drozd Marcin , Kosiorek Aneta , Kiczak Liliana , Bania Jacek , Ponikowski Piotr , Jankowska Ewa A.
Published: April 2021

Cardiac fibroblasts and cardiomyocytes are the main cells involved in the pathophysiology of myocarditis (MCD). These cells are especially sensitive to changes in iron homeostasis, which is extremely important for the optimal maintenance of crucial cellular processes. However, the exact role of iron status in the pathophysiology of MCD remains unknown. We cultured primary human cardiomyocytes (hCM) and cardiofibroblasts (hCF) with sera from acute MCD patients and healthy controls to mimic the effects of systemic inflammation on these cells. Next, we performed an initial small-scale (n = 3 per group) RNA sequencing experiment to investigate the global cellular response to the exposure on sera. In both cell lines, transcriptomic data analysis revealed many alterations in gene expression, which are related to disturbed canonical pathways and the progression of cardiac diseases. Moreover, hCM exhibited changes in the iron homeostasis pathway. To further investigate these alterations in sera-treated cells, we performed a larger-scale (n = 10 for controls, n = 18 for MCD) follow-up study and evaluated the expression of genes involved in iron metabolism. In both cell lines, we demonstrated an increased expression of transferrin receptor 1 (TFR1) and ferritin in MCD serum-treated cells as compared to controls, suggesting increased iron demand. Furthermore, we related TFR1 expression with the clinical profile of patients and showed that greater iron demand in sera-treated cells was associated with higher inflammation score (interleukin 6 (IL-6), C-reactive protein (CRP)) and advanced neurohormonal activation (NT-proBNP) in patients. Collectively, our data suggest that the malfunctioning of cardiomyocytes and cardiofibroblasts in the course of MCD might be related to alterations in the iron homeostasis.
Role of Structural and Non-Structural Proteins and Therapeutic Targets of SARS-CoV-2 for COVID-19
Authors: Yadav Rohitash , Chaudhary Jitendra Kumar , Jain Neeraj , Chaudhary Pankaj Kumar , Khanra Supriya , Dhamija Puneet , Sharma Ambika , Kumar Ashish , Handu Shailendra
Published: April 2021

Coronavirus belongs to the family of Coronaviridae, comprising single-stranded, positive-sense RNA genome (+ ssRNA) of around 26 to 32 kilobases, and has been known to cause infection to a myriad of mammalian hosts, such as humans, cats, bats, civets, dogs, and camels with varied consequences in terms of death and debilitation. Strikingly, novel coronavirus (2019-nCoV), later renamed as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), and found to be the causative agent of coronavirus disease-19 (COVID-19), shows 88% of sequence identity with bat-SL-CoVZC45 and bat-SL-CoVZXC21, 79% with SARS-CoV and 50% with MERS-CoV, respectively. Despite key amino acid residual variability, there is an incredible structural similarity between the receptor binding domain (RBD) of spike protein (S) of SARS-CoV-2 and SARS-CoV. During infection, spike protein of SARS-CoV-2 compared to SARS-CoV displays 10–20 times greater affinity for its cognate host cell receptor, angiotensin-converting enzyme 2 (ACE2), leading proteolytic cleavage of S protein by transmembrane protease serine 2 (TMPRSS2). Following cellular entry, the ORF-1a and ORF-1ab, located downstream to 5′ end of + ssRNA genome, undergo translation, thereby forming two large polyproteins, pp1a and pp1ab. These polyproteins, following protease-induced cleavage and molecular assembly, form functional viral RNA polymerase, also referred to as replicase. Thereafter, uninterrupted orchestrated replication-transcription molecular events lead to the synthesis of multiple nested sets of subgenomic mRNAs (sgRNAs), which are finally translated to several structural and accessory proteins participating in structure formation and various molecular functions of virus, respectively. These multiple structural proteins assemble and encapsulate genomic RNA (gRNA), resulting in numerous viral progenies, which eventually exit the host cell, and spread infection to rest of the body. In this review, we primarily focus on genomic organization, structural and non-structural protein components, and potential prospective molecular targets for development of therapeutic drugs, convalescent plasm therapy, and a myriad of potential vaccines to tackle SARS-CoV-2 infection.
A New Strain of Christensenella minuta as a Potential Biotherapy for Obesity and Associated Metabolic Diseases
Authors: Mazier Wilfrid , Le Corf Katy , Martinez Ccori , Tudela Héloïse , Kissi Déborah , Kropp Camille , Coubard Chrislain , Soto Marion , Elustondo Frédéric , Rawadi Georges , Claus Sandrine P.
Published: April 2021

Obesity is associated with gut microbiota dysbiosis, characterized by a high Firmicutes/Bacteroidetes ratio. Gut-dwelling bacteria of the Christensenellaceae family have been proposed to act as keystones of the human gut ecosystem and to prevent adipogenesis. The objectives of the present study were to demonstrate the antiobesity potential of a new strain of Christensenella minuta in preclinical models and explore related mechanisms of action. The antiobesity potential of C. minuta DSM33407 was assessed in a diet-induced obesity mouse model. Changes in hepatic lipid metabolism were explored using targeted transcriptomics. Effects on gut microbiota were further assessed in a humanized Simulator of the Human Intestinal Microbial Ecosystem (SHIME®) model inoculated with obese fecal samples. Shotgun metagenomics was applied to study microbial community structures in both models. C. minuta DSM33407 protected from diet-induced obesity and regulated associated metabolic markers such as glycemia and leptin. It also regulated hepatic lipid metabolism through a strong inhibition of de novo lipogenesis and maintained gut epithelial integrity. In the humanized SHIME® model, these effects were associated with modulations of the intestinal microbiota characterized by a decreased Firmicutes/Bacteroidetes ratio. These data indicate that C. minuta DSM33407 is a convincing therapeutic candidate for the management of obesity and associated metabolic disorders.
A2 Bovine Milk and Caprine Milk as a Means of Remedy for Milk Protein Allergy
Authors: Park Young W. , Haenlein George F. W.
Published: April 2021

A new type of cow’s milk, called A2 milk, has appeared in the dairy aisles of supermarkets in recent years. Cows’ milk generally contains two major types of beta-casein as A1 and A2 types, although there are 13 genetic variants of β-casein: A1, A2, A3, A4, B, C, D, E, F, H1, H2, I and G. Studies have shown that A1 β-casein may be harmful, and A2 β-casein is a safer choice for human health especially in infant nutrition and health. The A2 cow milk is reportedly easier to digest and better absorb than A1 or other types of milk. The structure of A2 cow’s milk protein is more comparable to human breast milk, as well as milk from goats, sheep and buffalo. Digestion of A1 type milk produces a peptide called β-casomorphin-7 (BCM-7), which is implicated with adverse gastrointestinal effects on milk consumption. In addition, bovine milk contains predominantly αs1-casein and low levels or even absent in αs2-casein, whereby caprine milk has been recommended as an ideal substitute for patients suffering from allergies against cow milk protein or other food sources. Since goat milk contains relatively low levels of αs1-casein or negligible its content, and αs2-casein levels are high in the milk of most dairy goat breeds, it is logical to assume that children with a high milk sensitivity to αs1-casein should tolerate goat milk well. Cow milk protein allergy (CMPA) is considered a common milk digestive and metabolic disorder or allergic disease with various levels of prevalence from 2.5% in children during the first 3 years of life to 12–30% in infants less than 3 months old, and it can go up to even as high as 20% in some countries. CMPA is an IgE-mediated allergy where the body starts to produce IgE antibodies against certain protein (allergens) such as A1 milk and αs1-casein in bovine milk. Studies have shown that ingestion of β-casein A1 milk can cause ischemic heart disease, type-1 diabetes, arteriosclerosis, sudden infant death syndrome, autism, schizophrenia, etc. The knowledge of bovine A2 milk and caprine αs2-casein has been utilized to rescue CMPA patients and other potential disease problems. This knowledge has been genetically applied to milk production in cows or goats or even whole herds of the two species. This practice has happened in California and Ohio, as well as in New Zealand, where this A2 cow milk has been now advanced commercially. In the USA, there have been even promotions of bulls, whose daughters have been tested homozygous for the A2 β-casein protein.
From STEAM to CHEER: A Case Study of Design Education Development in Taiwan
Authors: Lin Chinlon , Huang Jianping , Lin Rungtai
Published: April 2021

The purpose of this study is to provide other developing countries in the region a reference on the successful design education reformation in Taiwan. The study first reviews Taiwan’s economic and design development to show their interconnection with local culture and the global market. Next, the study explores Taiwan’s design education development which transforms from adopting STEM (science, technology, engineering, mathematics) to STEAM (science, technology, engineering, art, mathematics) in secondary school, and understands how it overcomes challenges by the help of both public and private sectors. Last, a conceptual framework is proposed to present and study Taiwan’s design education development. The result from case studies validates that STEAM can reach SAD (science, arts, and design) in higher education and CHEER (collaboration, humanity, empathy, ecology, and renaissance) in design practice. Therefore, the result and implications provided by this study can serve as a reference for other countries in the region who share similar cultural and socioeconomic development and future goals as Taiwan.
Cleaning of Floating Photovoltaic Systems: A Critical Review on Approaches from Technical and Economic Perspectives
Authors: Zahedi Rafi , Ranjbaran Parisa , Gharehpetian Gevork B. , Mohammadi Fazel , Ahmadiahangar Roya
Published: April 2021

There are some environmental factors, such as ambient temperature, dust, etc., which cause a reduction in the efficiency of Photovoltaic (PV) systems. Installation of PV panels on the water surface, commonly known as Floating Photovoltaic (FPV) systems, is one solution to employ PV panels in a cooler environment, achieve higher efficiency, and reduce water evaporation. FPV systems open up new opportunities for scaling up solar generating capacity, especially in countries with high population density and valuable lands, as well as countries with high evaporation rates and water resources deficiency. Since the FPV system is an almost new concept, its cleaning techniques have not been comprehensively studied. While FPV systems are located on the surface of water resources and reservoirs, the water quality can limit the application of different cleaning techniques. Therefore, this paper investigates different techniques of FPV systems cleaning and categorizes them into water-based and water-free approaches. In addition, their cleaning frequencies, as well as economic aspects, are presented and discussed to determine their merits and demerits for using them in FPV systems.
Analysis of the Possibility of Disinfecting Surfaces Using Portable Foggers in the Era of the SARS-CoV-2 Epidemic
Authors: Ochowiak Marek , Krupińska Andżelika , Włodarczak Sylwia , Matuszak Magdalena , Woziwodzki Szymon , Szulc Tomasz
Published: April 2021

The SARS-CoV-2 pandemic has resulted in the need for increased surface disinfection. For this purpose, biocides, UV-C radiation, or ozonation can be used. The most commonly used are biocides that can be deposited on the surface with the use of various devices, including foggers. The disinfection efficiency is related to the size of the aerosol droplets formed and their distribution. This paper specifies the distribution of droplet diameters and mean droplet diameters obtained during the use of a commercial fogger. It was shown that the droplet diameters formed were mainly in the range of up to 30–40 μm. A ceramic filter allowed for a larger number of smaller droplets and a limitation in the number of droplets with larger diameters. The results are important in the context of fighting the virus in hard-to-reach places where battery devices can be used.
Experimental Investigation of the Movement of an Offshore Floating Platform in Straight Wind, Tornadic Wind, and Downburst Conditions
Authors: Nichol Sarah , Carriveau Rupp , Miller Lindsay , Ting D. S-K. , Romanic Djordje , Costache Adrian , Hangan Horia
Published: April 2021

There is growing interest in multi-purpose offshore floating platforms that: harvest energy from the sun, wind, water, and waves; desalinize water; host agriculture and aquaculture; and house residents. While there are some basic commonalities with well established, oil and gas platforms, lighter variants are functionally different with little wind research coverage. Here, we investigate a floating, multi-purpose, light duty platform under 1:150 scaled straight atmospheric boundary layer wind (ABL), tornado like vortices (TLV), and downburst (DB) conditions. The experiments examined the movement of a 1:150 geometrically scaled platform with six degrees of freedom and two mooring Configurations. Four Configurations are studied, (1) Loosely moored platform, (2) Tightly moored platform, (3) Platform with ballast, and (4) Platform with ballast and weight on the deck. DB winds produced the greatest movement, followed by the TLV winds. Little movement was seen under the ABL winds. Loosely moored platforms moved more than tightly moored.
Will the Management Structure of Energy Administrators Affect the Achievement of the Electrical Efficiency Mandatory Target for Taiwan Factories?
Authors: Liao Feng-Fan , Chen Wun-Hwa
Published: April 2021

Since 2014, Taiwan has promoted a 1% annual electricity saving target to promote electrical efficiency efforts. As the industrial sector accounts for approximately 60% of the overall electricity consumption of Taiwan, this sector presents the greatest opportunity for improving Taiwan’s overall energy efficiency. Here, the energy audit data of industrial energy users are analyzed via logistic regression to understand the factors impacting their likelihood of achieving the targeted 1% electricity saving. Of the variables under study, the number of employees and the rank of the energy administrator were significantly correlated with the likelihood of reaching the electricity saving target. Within the management structure of the factory, energy users with higher-ranking energy administrators are more likely to achieve the targeted 1% electricity saving. As it is impractical to rapidly increase the number of employees, higher-ranking employees, i.e., factory executives, should be appointed as energy administrators to improve users’ electrical efficiency and thus reach the targeted 1% annual electricity saving. Based on the findings of our research, we put forward a point of view that in addition to the introduction of new technologies to improve energy efficiency, it can also be achieved through adjustments to the management structure of energy administration.
Mobility and Bioavailability of Metal(loid)s in a Fluvial System Affected by the Mining and Industrial Processing of Pb
Authors: Cortada Unai , Hidalgo María Carmen , Martínez Julián , de la Torre María José
Published: April 2021

The abandoned mining district of Linares (South Spain) is marked with waste from the mining and the processing of metal ores that pose an environmental hazard to watercourses. A combined analysis of waste, sediments and water was carried out to analyse the impact of a smelter on Baños Creek. The composition of the facility waste was determined using X-ray diffractometry and scanning electron microscopy. The total contents of the metal(loid)s in the waters and sediments of the watercourse were analysed, and sequential metal(loid) extraction of solid samples was carried out. The facility wastes consisted mainly of secondary minerals, such as natropharmacosiderite and spertiniite, as well as rare metal salts, such as mopungite and NaPb2(CO3)2(OH). The leachates generated by these wastes were highly alkaline, with a pH of 10 and a total dissolved solids concentration of approximately 9 g L−1. This Na-bicarbonate-type water had an As concentration above 200 mg L−1 and elevated levels of Pb, Sb and Zn (5029 µg L−1, 841 µg L−1 and 525 µg L−1, respectively). This highly contaminated lixiviate had a significant effect on the chemical quality of the waters and the bioavailability of metal(loid)s in the creek sediments, especially in the headwaters. In this zone, the As, Pb, Sb and Zn concentrations in the most mobile fraction of the sediments reached 1035 mg kg−1, 261 mg kg−1, 45 mg kg−1 and 30 mg kg−1, respectively. By comparison, smelter slag and mining waste have a much lower impact on the waters and the mobile fraction of the sediments, while significantly increasing the total concentration of these potentially toxic elements in creek sediments.
Do Rural Second Homes Shape Commensal Microbiota of Urban Dwellers? A Pilot Study among Urban Elderly in Finland
Authors: Saarenpää Mika , Roslund Marja , Puhakka Riikka , Grönroos Mira , Parajuli Anirudra , Hui Nan , Nurminen Noora , Laitinen Olli , Hyöty Heikki , Cinek Ondrej , Sinkkonen Aki ,   the ADELE Research Group
Published: April 2021

According to the hygiene and biodiversity hypotheses, increased hygiene levels and reduced contact with biodiversity can partially explain the high prevalence of immune-mediated diseases in developed countries. A disturbed commensal microbiota, especially in the gut, has been linked to multiple immune-mediated diseases. Previous studies imply that gut microbiota composition is associated with the everyday living environment and can be modified by increasing direct physical exposure to biodiverse materials. In this pilot study, the effects of rural-second-home tourism were investigated on the gut microbiota for the first time. Rural-second-home tourism, a popular form of outdoor recreation in Northern Europe, North America, and Russia, has the potential to alter the human microbiota by increasing exposure to nature and environmental microbes. The hypotheses were that the use of rural second homes is associated with differences in the gut microbiota and that the microbiota related to health benefits are more diverse or common among the rural-second-home users. Based on 16S rRNA Illumina MiSeq sequencing of stool samples from 10 urban elderly having access and 15 lacking access to a rural second home, the first hypothesis was supported: the use of rural second homes was found to be associated with lower gut microbiota diversity and RIG-I-like receptor signaling pathway levels. The second hypothesis was not supported: health-related microbiota were not more diverse or common among the second-home users. The current study encourages further research on the possible health outcomes or causes of the observed microbiological differences. Activities and diet during second-home visits, standard of equipment, surrounding environment, and length of the visits are all postulated to play a role in determining the effects of rural-second-home tourism on the gut microbiota.