bluuebunny/crossref_metadata_2025 huggingface dataset:
Fatty Acids: An Insight into the Pathogenesis of Neurodegenerative Diseases and Therapeutic Potential
Authors: Vesga-Jiménez Diego Julián , Martin Cynthia , Barreto George E. , Aristizábal-Pachón Andrés Felipe , Pinzón Andrés , González Janneth
Published: February 2022

One of the most common lipids in the human body is palmitic acid (PA), a saturated fatty acid with essential functions in brain cells. PA is used by cells as an energy source, besides being a precursor of signaling molecules and protein tilting across the membrane. Although PA plays physiological functions in the brain, its excessive accumulation leads to detrimental effects on brain cells, causing lipotoxicity. This mechanism involves the activation of toll-like receptors (TLR) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways, with the consequent release of pro-inflammatory cytokines, increased production of reactive oxygen species (ROS), endoplasmic reticulum (ER) stress, and autophagy impairment. Importantly, some of the cellular changes induced by PA lead to an augmented susceptibility to the development of Alzheimer’s and Parkinson´s diseases. Considering the complexity of the response to PA and the intrinsic differences of the brain, in this review, we provide an overview of the molecular and cellular effects of PA on different brain cells and their possible relationships with neurodegenerative diseases (NDs). Furthermore, we propose the use of other fatty acids, such as oleic acid or linoleic acid, as potential therapeutic approaches against NDs, as these fatty acids can counteract PA’s negative effects on cells.
Function of the Nuclear Transport Machinery in Maintaining the Distinctive Compositions of the Nucleus and Cytoplasm
Authors: Stewart Murray
Published: February 2022

Although the separation of transcription and translation, mediated by the nuclear envelope, is the defining characteristic of Eukaryotes, the barrier between the nuclear and cytoplasmic compartments needs to be semipermeable to enable material to be moved between them. Moreover, each compartment needs to have a distinctive complement of macromolecules to mediate specific functions and so movement between them needs to be controlled. This is achieved through the selective active transport of macromolecules through the nuclear pores that stud the nuclear envelope, and which serve as a conduit between these compartments. Nuclear pores are huge cylindrical macromolecular assemblies and are constructed from the order of 30 different proteins called nucleoporins. Nuclear pores have a central transport channel that is filled with a dense network of natively unfolded portions of many different nuclear pore proteins (nucleoporins or nups). This network generates a barrier that impedes, but does not entirely prevent, the diffusion of many macromolecules through the pores. The rapid movement of a range of proteins and RNAs through the pores is mediated by a range of transport factors that bind their cargo in one compartment and release it in the other. However, although as their size increases the diffusion of macromolecules through nuclear pores is progressively impaired, additional mechanisms, including the binding of some macromolecules to immobile components of each compartment and also the active removal of macromolecules from the inappropriate compartment, are needed to fully maintain the distinctive compositions of each compartment.
Substance P, A Promising Therapeutic Target in Musculoskeletal Disorders
Authors: Ko Kyung Rae , Lee Hyunil , Han Soo-Hong , Ahn Wooyeol , Kim Do Kyung , Kim Il-Su , Jung Bo Sung , Lee Soonchul
Published: February 2022

A large number of studies have focused on the role of substance P (SP) and the neurokinin-1 receptor (NK1R) in the pathogenesis of a variety of medical conditions. This review provides an overview of the role of the SP-NK1R pathway in the pathogenesis of musculoskeletal disorders and the evidence for its role as a therapeutic target for these disorders, which are major public health problems in most countries. To summarize, the brief involvement of SP may affect tendon healing in an acute injury setting. SP combined with an adequate conjugate can be a regenerative therapeutic option in osteoarthritis. The NK1R antagonist is a promising agent for tendinopathy, rheumatoid arthritis, and osteoarthritis. Research on the SP-NK1R pathway will be helpful for developing novel drugs for osteoporosis.
Phosphatidylcholine Enhances Homeostasis in Peach Seedling Cell Membrane and Increases Its Salt Stress Tolerance by Phosphatidic Acid
Authors: Sun Maoxiang , Liu Xiaolong , Gao Huaifeng , Zhang Binbin , Peng Futian , Xiao Yuansong
Published: February 2022

Salt stress is a major adverse abiotic factor seriously affecting fruit tree growth and development. It ultimately lowers fruit quality and reduces yield. Phosphatidylcholine (PC) is an important cell membrane component that is critical for cell structure and membrane stability maintenance. In this study, we found that the addition of external PC sources significantly increased the tolerance of one-year-old peach trees, Prunus persica (L.) Batsch., to salt stress and attenuated their damage. The effect of exogenous application of 200 mg/L PC exerted the most significant positive effect. Its use caused seedling leaf stomatal opening, contributing to normal gas exchange. Moreover, beneficial effects were exerted also to the root system, which grew normally under salt stress. Meanwhile, phospholipase D activity in the cell was promoted. The production of phosphatidic acid (PA) was enhanced by increased decomposition of phospholipids; PA serves as a secondary messenger involved in plant biological process regulation and the reduction in the reactive oxygen species- and peroxide-induced damage caused by salt stress. The possible mechanism of action is via promoted plant osmotic regulation and tolerance to salt stress, reducing salt stress-induced injury to plants.
Development of VPC-70619, a Small-Molecule N-Myc Inhibitor as a Potential Therapy for Neuroendocrine Prostate Cancer
Authors: Ton Anh-Tien , Foo Jane , Singh Kriti , Lee Joseph , Kalyta Anastasia , Morin Helene , Perez Carl , Ban Fuqiang , Leblanc Eric , Lallous Nada , Cherkasov Artem
Published: February 2022

The Myc family of transcription factors are involved in the development and progression of numerous cancers, including prostate cancer (PCa). Under the pressure of androgen receptor (AR)-directed therapies resistance can occur, leading to the lethal form of PCa known as neuroendocrine prostate cancer (NEPC), characterized among other features by N-Myc overexpression. There are no clinically approved treatments for NEPC, translating into poor patient prognosis and survival. Therefore, there is a pressing need to develop novel therapeutic avenues to treat NEPC patients. In this study, we investigate the N-Myc-Max DNA binding domain (DBD) as a potential target for small molecule inhibitors and utilize computer-aided drug design (CADD) approaches to discover prospective hits. Through further exploration and optimization, a compound, VPC-70619, was identified with notable anti-N-Myc potency and strong antiproliferative activity against numerous N-Myc expressing cell lines, including those representing NEPC.
Surface-Enhanced Raman Scattering from Dye Molecules in Silicon Nanowire Structures Decorated by Gold Nanoparticles
Authors: Ikramova Saltanat B. , Utegulov Zhandos N. , Dikhanbayev Kadyrjan K. , Gaipov Abduzhappar E. , Nemkayeva Renata R. , Yakunin Valery G. , Savinov Vladimir P. , Timoshenko Victor Yu
Published: February 2022

Silicon nanowires (SiNWs) prepared by metal-assisted chemical etching of crystalline silicon wafers followed by deposition of plasmonic gold (Au) nanoparticles (NPs) were explored as templates for surface-enhanced Raman scattering (SERS) from probe molecules of Methylene blue and Rhodamine B. The filling factor by pores (porosity) of SiNW arrays was found to control the SERS efficiency, and the maximal enhancement was observed for the samples with porosity of 55%, which corresponded to dense arrays of SiNWs. The obtained results are discussed in terms of the electromagnetic enhancement of SERS related to the localized surface plasmon resonances in Au-NPs on SiNW’s surfaces accompanied with light scattering in the SiNW arrays. The observed SERS effect combined with the high stability of Au-NPs, scalability, and relatively simple preparation method are promising for the application of SiNW:Au-NP hybrid nanostructures as templates in molecular sensorics.
Identification of Neoantigens in Cancer Cells as Targets for Immunotherapy
Authors: Okada Masahiro , Shimizu Kanako , Fujii Shin-ichiro
Published: February 2022

The clinical benefits of immune checkpoint blockage (ICB) therapy have been widely reported. In patients with cancer, researchers have demonstrated the clinical potential of antitumor cytotoxic T cells that can be reinvigorated or enhanced by ICB. Compared to self-antigens, neoantigens derived from tumor somatic mutations are believed to be ideal immune targets in tumors. Candidate tumor neoantigens can be identified through immunogenomic or immunopeptidomic approaches. Identification of neoantigens has revealed several points of the clinical relevance. For instance, tumor mutation burden (TMB) may be an indicator of immunotherapy. In various cancers, mutation rates accompanying neoantigen loads may be indicative of immunotherapy. Furthermore, mismatch repair-deficient tumors can be eradicated by T cells in ICB treatment. Hence, immunotherapies using vaccines or adoptive T-cell transfer targeting neoantigens are potential innovative strategies. However, significant efforts are required to identify the optimal epitopes. In this review, we summarize the recent progress in the identification of neoantigens and discussed preclinical and clinical studies based on neoantigens. We also discuss the issues remaining to be addressed before clinical applications of these new therapeutic strategies can be materialized.
Chemical Compounds Released from Specific Osteoinductive Bioactive Materials Stimulate Human Bone Marrow Mesenchymal Stem Cell Migration
Authors: Łukowicz Krzysztof , Zagrajczuk Barbara , Truchan Karolina , Niedzwiedzki Łukasz , Cholewa-Kowalska Katarzyna , Osyczka Anna M.
Published: February 2022

In this work, a poly(L-lactide-co-glycolide) (PLGA)-based composite was enriched with one of the following sol-gel bioactive glasses (SBG) at 50 wt.%: A1—40 mol% SiO2, 60 mol% CaO, CaO/SiO2 ratio of 1.50; S1—80 mol% SiO2, 20 mol% CaO, CaO/SiO2 ratio of 0.25; A2—40 mol% SiO2, 54 mol% CaO, 6 mol% P2O5, CaO/SiO2 ratio of 1.35; S2—80 mol% SiO2,16 mol% CaO, 4 mol% P2O5, CaO/SiO2 ratio of 0.20. The composites and PLGA control sheets were then soaked for 24 h in culture media, and the obtained condition media (CM) were used to treat human bone marrow stromal cells (hBMSCs) for 72 h. All CMs from the composites increased ERK 1/2 activity vs. the control PLGA CM. However, expressions of cell migration-related c-Fos, osteopontin, matrix metalloproteinase-2, C-X-C chemokine receptor type 4, vascular endothelial growth factor, and bone morphogenetic protein 2 were significantly increased only in cells treated with the CM from the A1/PLGA composite. This CM also significantly increased the rate of human BMSC migration but did not affect cell metabolic activity. These results indicate important biological markers that are upregulated by products released from the bioactive composites of a specific chemical composition, which may eventually prompt osteoprogenitor cells to colonize the bioactive material and accelerate the process of tissue regeneration.
Exploitation of the Antibacterial Properties of Photoactivated Curcumin as ‘Green’ Tool for Food Preservation
Authors: Munir Zunaira , Banche Giuliana , Cavallo Lorenza , Mandras Narcisa , Roana Janira , Pertusio Raffaele , Ficiarà Eleonora , Cavalli Roberta , Guiot Caterina
Published: February 2022

In the search for non-chemical and green methods to counteract the bacterial contamination of foods, the use of natural substances with antimicrobial properties and light irradiation at proper light waves has been extensively investigated. In particular, the combination of both techniques, called photodynamic inactivation (PDI), is based on the fact that some natural substances act as photosensitizers, i.e., produce bioactive effects under irradiation. Notably, curcumin is a potent natural antibacterial and effective photosensitizer that is able to induce photodynamic activation in the visible light range (specifically for blue light). Some practical applications have been investigated with particular reference to food preservation from bacterial contaminants.
Understanding the Molecular Mechanisms of Succinic Semialdehyde Dehydrogenase Deficiency (SSADHD): Towards the Development of SSADH-Targeted Medicine
Authors: Lee Henry H. C. , McGinty Gabrielle E. , Pearl Phillip L. , Rotenberg Alexander
Published: February 2022

Succinic semialdehyde dehydrogenase deficiency (SSADHD) is a rare genetic disorder caused by inefficient metabolic breakdown of the major inhibitory neurotransmitter, γ-aminobutyric acid (GABA). Pathologic brain accumulation of GABA and γ-hydroxybutyrate (GHB), a neuroactive by-product of GABA catabolism, leads to a multitude of molecular abnormalities beginning in early life, culminating in multifaceted clinical presentations including delayed psychomotor development, intellectual disability, hypotonia, and ataxia. Paradoxically, over half of patients with SSADHD also develop epilepsy and face a significant risk of sudden unexpected death in epilepsy (SUDEP). Here, we review some of the relevant molecular mechanisms through which impaired synaptic inhibition, astrocytic malfunctions and myelin defects might contribute to the complex SSADHD phenotype. We also discuss the gaps in knowledge that need to be addressed for the implementation of successful gene and enzyme replacement SSADHD therapies. We conclude with a description of a novel SSADHD mouse model that enables ‘on-demand’ SSADH restoration, allowing proof-of-concept studies to fine-tune SSADH restoration in preparation for eventual human trials.
Better Agreement of Human Transcriptomic and Proteomic Cancer Expression Data at the Molecular Pathway Activation Level
Authors: Raevskiy Mikhail , Sorokin Maxim , Zakharova Galina , Tkachev Victor , Borisov Nicolas , Kuzmin Denis , Kremenchutckaya Kristina , Gudkov Alexander , Kamashev Dmitry , Buzdin Anton
Published: February 2022

Previously, we have shown that the aggregation of RNA-level gene expression profiles into quantitative molecular pathway activation metrics results in lesser batch effects and better agreement between different experimental platforms. Here, we investigate whether pathway level of data analysis provides any advantage when comparing transcriptomic and proteomic data. We compare the paired proteomic and transcriptomic gene expression and pathway activation profiles obtained for the same human cancer biosamples in The Cancer Genome Atlas (TCGA) and the NCI Clinical Proteomic Tumor Analysis Consortium (CPTAC) projects, for a total of 755 samples of glioblastoma, breast, liver, lung, ovarian, pancreatic, and uterine cancers. In a CPTAC assay, expression levels of 15,112 protein-coding genes were profiled using the Thermo QE series of mass spectrometers. In TCGA, RNA expression levels of the same genes were obtained using the Illumina HiSeq 4000 engine for the same biosamples. At the gene level, absolute gene expression values are compared, whereas pathway-grade comparisons are made between the pathway activation levels (PALs) calculated using average sample-normalized transcriptomic and proteomic profiles. We observed remarkably different average correlations between the primary RNA- and protein expression data for different cancer types: Spearman Rho between 0.017 (p = 1.7 × 10−13) and 0.27 (p < 2.2 × 10−16). However, at the pathway level we detected overall statistically significantly higher correlations: averaged Rho between 0.022 (p < 2.2 × 10−16) and 0.56 (p < 2.2 × 10−16). Thus, we conclude that data analysis at the PAL-level yields results of a greater similarity when comparing high-throughput RNA and protein expression profiles.
Hexokinase 2 Inhibition and Biological Effects of BNBZ and Its Derivatives: The Influence of the Number and Arrangement of Hydroxyl Groups
Authors: Juszczak Karolina , Kubicka Anna , Kitel Radosław , Dzido Grzegorz , Łabieniec-Watała Magdalena , Zawadzki Serafin , Marczak Agnieszka , Walczak Krzysztof , Matczak Karolina , Tomczyk Mateusz D.
Published: February 2022

Hexokinase 2 (HK2), an enzyme of the sugar kinase family, plays a dual role in glucose metabolism and mediating cancer cell apoptosis, making it an attractive target for cancer therapy. While positive HK2 expression usually promotes cancer cells survival, silencing or inhibiting this enzyme has been found to improve the effectiveness of anti-cancer drugs and even result in cancer cell death. Previously, benitrobenrazide (BNBZ) was characterized as a potent HK2 inhibitor with good anti-cancer activity in mice, but the effect of its trihydroxy moiety (pyrogallol-like) on inhibitory activity and some cellular functions has not been fully understood. Therefore, the main goal of this study was to obtain the parent BNBZ (2a) and its three dihydroxy derivatives 2b–2d and to conduct additional physicochemical and biological investigations. The research hypothesis assumed that the HK2 inhibitory activity of the tested compounds depends on the number and location of hydroxyl groups in their chemical structure. Among many studies, the binding affinity to HK2 was determined and two human liver cancer cell lines, HepG2 and HUH7, were used and exposed to chemicals at various times: 24 h, 48 h and 72 h. The study showed that the modifications to the structures of the new BNBZ derivatives led to significant changes in their activities. It was also found that these compounds tend to aggregate and exhibit toxic effects. They were found to contribute to: (a) DNA damage, (b) increased ROS production, and (c) disruption of cell cycle progression. It was observed that, HepG2, occurred much more sensitive to the tested chemicals than the HUH7 cells; However, regardless of the used cell line it seems that the increase in the expression of HK2 in cancer cells compared to normal cells which have HK2 at a very low level, is a serious obstacle in anti-cancer therapy and efforts to find the effective inhibitors of this enzyme should be intensified.
The Pathogenesis of Cardiac Fibrosis: A Review of Recent Progress
Authors: Maruyama Kazuaki , Imanaka-Yoshida Kyoko
Published: February 2022

Fibrosis is defined as the excessive deposition of extracellular matrix (ECM) proteins in the interstitium. It is an essential pathological response to chronic inflammation. ECM protein deposition is initially protective and is critical for wound healing and tissue regeneration. However, pathological cardiac remodeling in excessive and continuous tissue damage with subsequent ECM deposition results in a distorted organ architecture and significantly impacts cardiac function. In this review, we summarized and discussed the histologic features of cardiac fibrosis with the signaling factors that control it. We evaluated the origin and characteristic markers of cardiac fibroblasts. We also discussed lymphatic vessels, which have become more important in recent years to improve cardiac fibrosis.
Exercise and Training Regulation of Autophagy Markers in Human and Rat Skeletal Muscle
Authors: Botella Javier , Jamnick Nicholas A. , Granata Cesare , Genders Amanda J. , Perri Enrico , Jabar Tamim , Garnham Andrew , Lazarou Michael , Bishop David J.
Published: February 2022

Autophagy is a key intracellular mechanism by which cells degrade old or dysfunctional proteins and organelles. In skeletal muscle, evidence suggests that exercise increases autophagosome content and autophagy flux. However, the exercise-induced response seems to differ between rodents and humans, and little is known about how different exercise prescription parameters may affect these results. The present study utilised skeletal muscle samples obtained from four different experimental studies using rats and humans. Here, we show that, following exercise, in the soleus muscle of Wistar rats, there is an increase in LC3B-I protein levels immediately after exercise (+109%), and a subsequent increase in LC3B-II protein levels 3 h into the recovery (+97%), despite no change in Map1lc3b mRNA levels. Conversely, in human skeletal muscle, there is an immediate exercise-induced decrease in LC3B-II protein levels (−24%), independent of whether exercise is performed below or above the maximal lactate steady state, which returns to baseline 3.5 h following recovery, while no change in LC3B-I protein levels or MAP1LC3B mRNA levels is observed. SQSTM1/p62 protein and mRNA levels did not change in either rats or humans following exercise. By employing an ex vivo autophagy flux assay previously used in rodents we demonstrate that the exercise-induced decrease in LC3B-II protein levels in humans does not reflect a decreased autophagy flux. Instead, effect size analyses suggest a modest-to-large increase in autophagy flux following exercise that lasts up to 24 h. Our findings suggest that exercise-induced changes in autophagosome content markers differ between rodents and humans, and that exercise-induced decreases in LC3B-II protein levels do not reflect autophagy flux level.
The Influence of Interaction between Cadmium with 17β-Estradiol, 2-Methoxyestradiol and 16α-Hydroxyestrone on Viability and p-Glycoprotein in Ovarian Cancer Cell Line
Authors: Sawicka Ewa , Saczko Jolanta , Kulbacka Julita , Szydełko Martyna , Szymańska Beata , Piwowar Agnieszka
Published: February 2022

Occupational and environmental exposure to xenoestrogens, a subgroup of endocrine disruptors (EDCs), can affect the endocrine system and increase the risk of cancer, primarily the hormone-dependent kind. This type of cancer includes ovarian cancer, which is the leading cause of death from gynecological tumors. The aim of this study was to assess the role of 17β-estradiol and its metabolites: 2-MeOE2, 16α-OHE1 in exposure to the metalloestrogen cadmium. The effect of interactions of cadmium with estrogens on the viability of cells in malignant ovarian cancer cells SKOV-3 was investigated, both in simultaneous action and in the pre-incubation model. There are no known interactions between estrogens and cadmium in ovarian cancer cells. Due to the frequent occurrence of multidrug resistance (MDR) in ovarian cancer, the effects of estrogens and cadmium on MDR in SKOV-3, measured as P-glycoprotein (P-gp), were assessed. An interaction study showed that E2 had an antagonistic effect on cadmium-induced cell damage, while 2-MeOE2 showed less of a protective effect in combination with CdCl2 than E2. There were two types of interaction: toxic synergism and beneficial antagonism. E2 and cadmium increased P-gp expression in SKOV-3 cells, while 2-MeOE2 decreased P-gp expression to a potentially beneficial effect on MDR prevention. The obtained results constitute an interesting starting point for further research in the field of interactions between estrogens and xenoestrogens in ovarian cancer.
Mesothelioma and Colorectal Cancer: Report of Four Cases with Synchronous and Metachronous Presentation
Authors: Serio Gabriella , Pezzuto Federica , Fortarezza Francesco , Marzullo Andrea , Delfino Maria Celeste , d’Amati Antonio , Romano Daniele Egidio , Maniglio Sonia , Caporusso Concetta , Lettini Teresa , Cavone Domenica , Vimercati Luigi
Published: February 2022

There is evidence that asbestos could play a role in the carcinogenesis of digestive cancers. The presence of asbestos fibres in histological samples from gastric, biliary, colon cancers has been reported, but the mechanism is still controversial. It has been hypothesised that asbestos reaches these sites, especially through contaminated water; however, some experimental studies have shown that the inhaled fibres are mobile, so they can migrate to many organs, directly or via blood and lymph flow. We report four unusual cases of colorectal cancers in patients with a long history of asbestos exposure who also developed synchronous or metachronous mesothelioma. We evaluated the roles of BRCA associated protein-1 (BAP1) and cyclin-dependent kinase inhibitor 2A (CDKN2A) in colon cancer and mesothelioma to support the hypothesis that BAP-1 and CDKN2A are tumour suppressor genes involved in disease progression, recurrence, or death in both digestive cancers and mesothelioma. Potentially, these markers may be used as predictors of worse prognosis, but we also stress the importance of clinical surveillance of exposed patients because asbestos could induce cancer in any organ.
Favipiravir Inhibits Hepatitis A Virus Infection in Human Hepatocytes
Authors: Sasaki-Tanaka Reina , Shibata Toshikatsu , Okamoto Hiroaki , Moriyama Mitsuhiko , Kanda Tatsuo
Published: February 2022

Hepatitis A virus (HAV) is a causative agent of acute hepatitis and can occasionally induce acute liver failure. However, specific potent anti-HAV drug is not available on the market currently. Thus, we investigated several novel therapeutic drugs through a drug repositioning approach, targeting ribonucleic acid (RNA)-dependent RNA polymerase and RNA-dependent deoxyribonucleic acid polymerase. In the present study, we examined the anti-HAV activity of 18 drugs by measuring the HAV subgenomic replicon and HAV HA11-1299 genotype IIIA replication in human hepatoma cell lines, using a reporter assay and real-time reverse transcription polymerase chain reaction, respectively. Mutagenesis of the HAV 5’ untranslated region was also examined by next-generation sequencing. These specific parameters were explored because lethal mutagenesis has emerged as a novel potential therapeutic approach to treat RNA virus infections. Favipiravir inhibited HAV replication in both Huh7 and PLC/PRF/5 cells, although ribavirin inhibited HAV replication in only Huh7 cells. Next-generation sequencing demonstrated that favipiravir could introduce nucleotide mutations into the HAV genome more than ribavirin. In conclusion, favipiravir could introduce nucleotide mutations into the HAV genome and work as an antiviral against HAV infection. Provided that further in vivo experiments confirm its efficacy, favipiravir would be useful for the treatment of severe HAV infection.
Synergistic and Detrimental Effects of Alcohol Intake on Progression of Liver Steatosis
Authors: Di Ciaula Agostino , Bonfrate Leonilde , Krawczyk Marcin , Frühbeck Gema , Portincasa Piero
Published: February 2022

Nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) are the most common liver disorders worldwide and the major causes of non-viral liver cirrhosis in the general population. In NAFLD, metabolic abnormalities, obesity, and metabolic syndrome are the driving factors for liver damage with no or minimal alcohol consumption. ALD refers to liver damage caused by excess alcohol intake in individuals drinking more than 5 to 10 daily units for years. Although NAFLD and ALD are nosologically considered two distinct entities, they show a continuum and exert synergistic effects on the progression toward liver cirrhosis. The current view is that low alcohol use might also increase the risk of advanced clinical liver disease in NAFLD, whereas metabolic factors increase the risk of cirrhosis among alcohol risk drinkers. Therefore, special interest is now addressed to individuals with metabolic abnormalities who consume small amounts of alcohol or who binge drink, for the role of light-to-moderate alcohol use in fibrosis progression and clinical severity of the liver disease. Evidence shows that in the presence of NAFLD, there is no liver-safe limit of alcohol intake. We discuss the epidemiological and clinical features of NAFLD/ALD, aspects of alcohol metabolism, and mechanisms of damage concerning steatosis, fibrosis, cumulative effects, and deleterious consequences which include hepatocellular carcinoma.
CXC Chemokine Signaling in Progression of Epithelial Ovarian Cancer: Theranostic Perspectives
Authors: Huang Xinxin , Hao Juncheng , Tan Yan Qin , Zhu Tao , Pandey Vijay , Lobie Peter E.
Published: February 2022

Patients with epithelial ovarian cancer (EOC) are often diagnosed at an advanced stage due to nonspecific symptoms and ineffective screening approaches. Although chemotherapy has been available and widely used for the treatment of advanced EOC, the overall prognosis remains dismal. As part of the intrinsic defense mechanisms against cancer development and progression, immune cells are recruited into the tumor microenvironment (TME), and this process is directed by the interactions between different chemokines and their receptors. In this review, the functional significance of CXC chemokine ligands/chemokine receptors (CXCL/CXCR) and their roles in modulating EOC progression are summarized. The status and prospects of CXCR/CXCL-based theranostic strategies in EOC management are also discussed.
Introducing the Architecture of FASTER: A Digital Ecosystem for First Responder Teams
Authors: Katsadouros Evangelos , Kogias Dimitrios G. , Patrikakis Charalampos Z. , Giunta Gabriele , Dimou Anastasios , Daras Petros
Published: February 2022

Emergency first responders play an important role during search and rescue missions, by helping people and saving lives. Thus, it is important to provide them with technology that will maximize their performance and their safety on the field of action. IFAFRI, the “International Forum to Advanced First Responder Innovation” has pointed out several capability gaps that are found in the existing solutions. Based on them, there is a need for the development of novel, modern digital solutions that will better assist responders by helping them on the field and, at the same time, better protect them. The work presented here introduces the logical architecture implemented in the Horizon 2020 project called FASTER (First responders Advanced technologies for Safe and efficienT Emergency Response), which is an innovating digital ecosystem for emergency first response teams. It is a system that meets the requirements of the consortium members but also fills all the gaps that IFARFI has pointed out and consists of mechanisms and tools for data communication, data analysis, monitoring, privacy protection and smart detection mechanisms.
Designing a Pest and Disease Outbreak Warning System for Farmers, Agronomists and Agricultural Input Distributors in East Africa
Authors: Brown Molly E. , Mugo Stephen , Petersen Sebastian , Klauser Dominik
Published: February 2022

Early warnings of the risks of pest and disease outbreaks are becoming more urgent, with substantial increases in threats to agriculture from invasive pests. With geospatial data improvements in quality and timeliness, models and analytical systems can be used to estimate potential areas at high risk of yield impacts. The development of decision support systems requires an understanding of what information is needed, when it is needed, and at what resolution and accuracy. Here, we report on a professional review conducted with 53 professional agronomists, retailers, distributors, and growers in East Africa working with the Syngenta Foundation for Sustainable Agriculture. The results showed that respondents reported fall armyworm, stemborers and aphids as being among the most common pests, and that crop diversification was a key strategy to reduce their impact. Chemical and cultural controls were the most common strategies for fall armyworm (FAW) control, and biological control was the least known and least used method. Of the cultural control methods, monitoring and scouting, early planting, and crop rotation with non-host crops were most used. Although pests reduced production, only 55% of respondents were familiar with early warning tools, showing the need for predictive systems that can improve farmer response.
Antennal Morphology and Fine Structure of Flagellar Sensilla in Hippoboscid Flies with Special Reference to Lipoptena fortisetosa (Diptera: Hippoboscidae)
Authors: Andreani Annalisa , Belcari Antonio , Sacchetti Patrizia , Romani Roberto
Published: February 2022

Lipoptena cervi (Linnaeus), Lipoptena fortisetosa Maa, Hippobosca equina Linnaeus, and Pseudolynchia canariensis (Macquart) are hematophagous ectoparasites that infest different animal species and occasionally bite humans. Hosts are located by a complex process involving different kinds of stimuli perceived mainly by specific sensory structures on the antennae, which are the essential olfactory organs. General antennal morphology, together with distribution and ultrastructure of sensilla, have been studied in detail with scanning and transmission electron microscopy approaches. Observations have revealed some common features among the four studied hippoboscids: (a) typical concealment of the flagellum inside the other two segments; (b) characteristic trabecular surface of the flagellum; (c) peculiar external microtrichia; (d) presence on the flagellum of basiconic sensilla and grooved peg coeloconic sensilla; (e) unarticulated arista. The ultrastructure of L. fortisetosa revealed that microtrichia and the flagellar reticulated cuticle are not innervated. Different roles have been hypothesized for the described antennal structures. Microtrichia and the reticulated cuticle could convey volatile compounds towards the flagellar sensory area. Peculiar sensory neurons characterize the unarticulated arista which could be able to detect temperature variations. Coeloconic sensilla could be involved in thermoreception, hygroreception, and carbon dioxide reception at long distances, while the poorly porous basiconic sensilla could play a role in the host odour perception at medium–short distances.
Echocardiographic Assessment of Atrial Function: From Basic Mechanics to Specific Cardiac Diseases
Authors: Inoue Katsuji , Kawakami Hiroshi , Akazawa Yusuke , Higashi Haruhiko , Higaki Takashi , Yamaguchi Osamu
Published: February 2022

The left and right atria serve as buffer chambers to control the flow of venous blood for ventricular filling. If an atrium is absent, blood does not flow effectively into the ventricle, leading to venous blood retention and low cardiac output. The importance of atrial function has become increasingly recognized, because left atrial (LA) function contributes to cardiac performance, and loss of LA function is associated with heart failure. LA volume change has been used for LA function assessment in experimental and clinical studies. In conjunction with LA pressure, the LA pressure–volume relationship provides a better understanding of LA mechanics. LA strain measurement by speckle tracking echocardiography was introduced to evaluate three components of LA function as a (booster) pump, reservoir and conduit. Furthermore, increasing evidence supports the theory that LA reservoir strain has prognostic utility in various cardiac diseases. In this review, we summarize LA contribution to maintain cardiac performance by evaluating LA function with echocardiography according to our experiences and previous reports. Furthermore, we discuss LA dysfunction in challenging cardiac diseases of cardiac amyloidosis and adult congenital heart disease.
Association between Concentric and Eccentric Isokinetic Torque and Unilateral Countermovement Jump Variables in Professional Soccer Players
Authors: Alves Bruno Mazziotti Oliveira , Scoz Robson Dias , Burigo Ricardo Lima , Ferreira Isabella Christina , Ramos Ana Paula Silveira , Mendes Jose Joao Baltazar , Ferreira Luciano Maia Alves , Amorim Cesar Ferreira
Published: February 2022

Isokinetic tests have been highly valuable to athletic analysis, but their cost and technical operation turn them inaccessible. The purpose of this study was to verify the correlation between unilateral countermovement jump variables and isokinetic data. Thirty-two male professional soccer players were subjected to the isokinetic testing of both knee extensors and flexors in concentric and eccentric muscle contractions. They also executed unilateral countermovement vertical jumps (UCMJ) to compare maximum height, ground reaction force, and impulse power with isokinetic peak torque. Data analysis was conducted through Pearson correlation and linear regression. A high correlation was found between dominant unilateral extensor concentric peak torque and the UCMJ maximum height of the dominant leg. The non-dominant leg jump showed a moderate correlation. No other variable showed statistical significance. Linear regression allowed the generation of two formulae to estimate the peak torque from UCMJ for dominant and non-dominant legs. Although few studies were found to compare our results, leading to more studies being needed, a better understanding of the unilateral countermovement jump may be used in the future as a substitute to the expensive and technically demanding isokinetic testing when it is unavailable, allowing the assessment of lower limb physical asymmetries in athletic or rehabilitation environments.
Ganoderma zonatum Is the Causal Agent of Basal Stem Rot in Oil Palm in Colombia
Authors: Castillo Sandra Yulieth , Rodríguez María Camila , González Luis Felipe , Zúñiga León Franky , Mestizo Yuri Adriana , Medina Héctor Camilo , Montoya Carmenza , Morales Anuar , Romero Hernán Mauricio , Sarria Greicy Andrea
Published: February 2022

Basal stem rot (BSR), caused by Ganoderma spp., is one of the most important emerging oil palm diseases in Colombia, and is restricted to two oil palm production areas in the country. To identify the causal agent of the disease, basidiocarp of oil palms affected by BSR were used to prepare isolates, and their pathogenicity was then assessed in pre-nursery plants. Four-month-old oil palm seedlings were inoculated with rubber wood (Hevea brasiliensis) blocks colonized with dikaryotic mycelia of Ganoderma. The incidence, severity, and symptoms of the pathogen were assessed. A multiregional analysis (ITS, rpb2, and tef1-α) was carried out to identify the isolates; all isolates were determined to be Ganoderma zonatum. Phylogenetic analyses with the three regions yielded concordant phylogenetic information and supported the distinction of the isolates with high bootstrap support. Seven isolates (CPBsZN-01-29, CPBsZN-02-30, CPBsZN-03-31, CPBsZN-04-34, CPBsZN-05-35, CPBsZN-06-36, and CPBsZN-07-38) were pathogenic in oil palm, with incidences greater than 90% and a maximum severity of 34%, and the highest severity index was found in isolates CPBsZN-03-31, CPBsZN-04-34, and CPBsZN-06-36. The pathogen was recovered from inoculated oil palms in all cases. This study reveals the pathogenic association of Ganoderma zonatum with BSR in Colombia.
Family Ownership, Corporate Governance and Risk-Taking
Authors: Otero-González Luis , Rodríguez-Gil Luis-Ignacio , Vivel-Búa Milagros , Tamayo-Herrera Aracely
Published: February 2022

This paper analyses the effect of family ownership and the characteristics of the board of directors on the risk assumed by Spanish non-financial companies. The sample consists of 176 Spanish non-financial companies listed on Spanish stock exchanges during the period 2012–2015. The results show that the level of family ownership concentration affects the level of exposure to risk non-linearly and confirms the importance of the characteristics of the board of directors in risk-taking.
Natural and Cultural Lost Landscape during the Holocene along the Central Tyrrhenian Coast (Italy)
Authors: D’Orefice Maurizio , Bellotti Piero , Bellotti Tiberio , Davoli Lina , Di Bella Letizia
Published: February 2022

Landscape evolution over the last 8000 years in three areas located along Tuscany, Latium, and Campania coasts (central Tyrrhenian) has been deduced through a morphological, stratigraphical, and historical approach considering the physical evolution and human activity. Between 8000 and 6000 yr BP, the Sea Level Rise (SLR) dominated and, near the river mouths, inlets occurred. In the Tuscany area, Mt. Argentario was an island and to SE of the Ansedonia promontory a lagoon occurred. The areas were covered by a dense forest and the human influence was negligible. Between 6000 and 4000 yr BP, humans organized settlements and activities, and a general coastline progradation occurred. A tombolo linked Mt. Argentario to the mainland. In the Tiber and Campania areas, coastal lakes and a strand plain developed. Between 4000 and 3000 yr BP, near Mt. Argentario, two tombolos enclosed a wide lagoon. At the SE of the Ansedonia promontory, the lagoon split into smaller water bodies. In the Tiber and Campania areas, delta cusps developed. The anthropogenic presence was widespread and forests decreased. During the last 3000 years, anthropic forcing increased when the Etruscans and Romans changed the territory through towns, salt pans, and ports. After the Roman period, natural forcing returned to dominate until the birth of the Italian State and technological evolution.
Predictors of Word and Text Reading Fluency of Deaf Children in Bilingual Deaf Education Programmes
Authors: Ormel Ellen , Giezen Marcel R. , Knoors Harry , Verhoeven Ludo , Gutierrez-Sigut Eva
Published: February 2022

Reading continues to be a challenging task for most deaf children. Bimodal bilingual education creates a supportive environment that stimulates deaf children’s learning through the use of sign language. However, it is still unclear how exposure to sign language might contribute to improving reading ability. Here, we investigate the relative contribution of several cognitive and linguistic variables to the development of word and text reading fluency in deaf children in bimodal bilingual education programmes. The participants of this study were 62 school-aged (8 to 10 years old at the start of the 3-year study) deaf children who took part in bilingual education (using Dutch and Sign Language of The Netherlands) and 40 age-matched hearing children. We assessed vocabulary knowledge in speech and sign, phonological awareness in speech and sign, receptive fingerspelling ability, and short-term memory at time 1 (T1). At times 2 (T2) and 3 (T3), we assessed word and text reading fluency. We found that (1) speech-based vocabulary strongly predicted word and text reading at T2 and T3, (2) fingerspelling ability was a strong predictor of word and text reading fluency at T2 and T3, (3) speech-based phonological awareness predicted word reading accuracy at T2 and T3 but did not predict text reading fluency, and (4) fingerspelling and STM predicted word reading latency at T2 while sign-based phonological awareness predicted this outcome measure at T3. These results suggest that fingerspelling may have an important function in facilitating the construction of orthographical/phonological representations of printed words for deaf children and strengthening word decoding and recognition abilities.
Nickel Oxide Films Deposited by Sol-Gel Method: Effect of Annealing Temperature on Structural, Optical, and Electrical Properties
Authors: Ivanova Tatyana , Harizanova Antoaneta , Shipochka Maria , Vitanov Petko
Published: February 2022

In our study, transparent and conductive films of NiOx were successfully deposited by sol-gel technology. NiOx films were obtained by spin coating on glass and Si substrates. The vibrational, optical, and electrical properties were studied as a function of the annealing temperatures from 200 to 500 °C. X-ray Photoelectron (XPS) spectroscopy revealed that NiO was formed at the annealing temperature of 400 °C and showed the presence of Ni+ states. The optical transparency of the films reached 90% in the visible range for 200 °C treated samples, and it was reduced to 76–78% after high-temperature annealing at 500 °C. The optical band gap of NiOx films was decreased with thermal treatments and the values were in the range of 3.92–3.68 eV. NiOx thin films have good p-type electrical conductivity with a specific resistivity of about 4.8 × 10−3 Ω·cm. This makes these layers suitable for use as wideband semiconductors and as a hole transport layer (HTL) in transparent solar cells.
Distribution Characteristics of Screw Axes Belonging to General Three-System of Screws
Authors: Zhang Leilei , Zhao Yanzhi , Wei Xianhe
Published: February 2022

The cylindroid describes the exact distribution of the ∞1 screw axes of the general two-system of screws. For the general three-system, this article introduces the surface on which lies the position vector endpoints of its ∞2 screw axes, and then develops the finite distribution zone in which they most densely distribute. In particular, this paper explores the inner structure of the zone by partitioning the general three-system into ∞1 two-subsystems, and then reveals the principle of constructing the distribution space of the general three-system by that of the general two-system in Euclidean three-space. In pursuit of a generalized decomposition method, we propose the varying-pitch ruled surface carrying the screws whose pitch value continuously varies according to any desired function rule, based on the pitch-hyperboloid carrying all the equal-pitch screws. This investigation provides some useful guides for the axode planning and then the motion planning of three degree-of-freedom parallel mechanisms.
Deposition of Crystalline GdIG Samples Using Metal Organic Decomposition Method
Authors: Kim Hyeongyu , Van Phuoc-Cao , Jung Hyeonjung , Yang Jiseok , Jo Younghun , Yoo Jung-Woo , Park Albert M. , Jeong Jong-Ryul , Kim Kab-Jin
Published: February 2022

Fabrication of high quality ferrimagnetic insulators is an essential step for ultrafast magnonics, which utilizes antiferromagnetic exchange of the ferrimagnetic materials. In this work, we deposit high-quality GdIG thin films on a (111)-oriented GGG substrate using the Metal Organic Decomposition (MOD) method, a simple and high throughput method for depositing thin film materials. We postannealed samples at various temperatures and examined the effect on structural properties such as crystallinity and surface morphology. We found a transition in the growth mode that radically changes the morphology of the film as a function of annealing temperature and obtained an optimal annealing temperature for a uniform thin film with high crystallinity. Optimized GdIG has a high potential for spin wave applications with a low damping parameter in the order of 10−3, which persists down to cryogenic temperatures.