bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulation of the Immune Checkpoint Indoleamine 2,3-Dioxygenase Expression by Epstein–Barr Virus
Authors: Sawada Leila , Vallinoto Antonio Carlos Rosário , Brasil-Costa Igor
Published: December 2021

Epstein–Barr virus (EBV) is an oncovirus ubiquitously distributed and associated with different types of cancer. The reason why only a group of infected people develop cancer is still unknown. EBV-associated cancers represent about 1.8% of all cancer deaths worldwide, with more than 150,000 new cases of cancer being reported annually. Since EBV-associated cancers are described as more aggressive and more resistant to the usual treatment compared to EBV-negative ones, the recent introduction of monoclonal antibodies (mAbs) targeting immune checkpoints (ICs) in the treatment of cancer patients represents a possible therapy for EBV-associated diseases. However, the current mAb therapies available still need improvement, since a group of patients do not respond well to treatment. Therefore, the main objective of this review is to summarize the progress made regarding the contribution of EBV infection to the expression of the IC indoleamine 2,3-dioxygenase (IDO) thus far. This IC has the potential to be used as a target in new immune therapies, such as mAbs. We hope that this work helps the development of future immunotherapies, improving the prognosis of EBV-associated cancer patients.
Exploring the Value of BRD9 as a Biomarker, Therapeutic Target and Co-Target in Prostate Cancer
Authors: Barma Nafisa , Stone Timothy C. , Carmona Echeverria Lina Maria , Heavey Susan
Published: December 2021

Background and aims: Despite recent advances in advanced prostate cancer treatments, clinical biomarkers or treatments for men with such cancers are imperfect. Targeted therapies have shown promise, but there remain fewer actionable targets in prostate cancer than in other cancers. This work aims to characterise BRD9, currently understudied in prostate cancer, and investigate its co-expression with other genes to assess its potential as a biomarker and therapeutic target in human prostate cancer. Materials and methods: Omics data from a total of 2053 prostate cancer patients across 11 independent datasets were accessed via Cancertool and cBioPortal. mRNA M.expression and co-expression, mutations, amplifications, and deletions were assessed with respect to key clinical parameters including survival, Gleason grade, stage, progression, and treatment. Network and pathway analysis was carried out using Genemania, and heatmaps were constructed using Morpheus. Results: BRD9 is overexpressed in prostate cancer patients, especially those with metastatic disease. BRD9 expression did not differ in patients treated with second generation antiandrogens versus those who were not. BRD9 is co-expressed with many genes in the SWI/SNF and BET complexes, as well as those in common signalling pathways in prostate cancer. Summary and conclusions: BRD9 has potential as a diagnostic and prognostic biomarker in prostate cancer. BRD9 also shows promise as a therapeutic target, particularly in advanced prostate cancer, and as a co-target alongside other genes in the SWI/SNF and BET complexes, and those in common prostate cancer signalling pathways. These promising results highlight the need for wider experimental inhibition and co-targeted inhibition of BRD9 in vitro and in vivo, to build on the limited inhibition data available.
New Insights into the Role of Cysteine Cathepsins in Neuroinflammation
Authors: Pišlar Anja , Bolčina Lara , Kos Janko
Published: December 2021

Neuroinflammation, which is mediated by microglia and astrocytes, is associated with the progression of neurodegenerative diseases. Increasing evidence shows that activated microglia induce the expression and secretion of various lysosomal cathepsins, particularly during the early stage of neuroinflammation. This trigger signaling cascade that aggravate neurodegeneration. To date, most research on neuroinflammation has focused on the role of cysteine cathepsins, the largest cathepsin family. Cysteine cathepsins are primarily responsible for protein degradation in lysosomes; however, they also play a role in regulating a number of other important physiological and pathological processes. This review focuses on the functional roles of cysteine cathepsins in the central nervous system during neuroinflammation, with an emphasis on their roles in the polarization of microglia and neuroinflammation signaling, which in turn causes neuronal death and thus neurodegeneration.
SNCA 3′ UTR Genetic Variants in Patients with Parkinson’s Disease
Authors: Blažeković Antonela , Jerčić Kristina Gotovac , Borovečki Fran
Published: December 2021

The SNCA (Synuclein Alpha) gene represents a major risk gene for Parkinson’s disease (PD) and SNCA polymorphisms have been associated with the common sporadic form of PD. Numerous Genome-Wide Association Studies showed strong signals located in the SNCA 3′ UTR (untranslated region) region indicating that variants in 3′ UTRs of PD-associated genes could contribute to neurodegeneration and may regulate the risk for PD. Genetic variants in 3′ UTR can affect miRNA activity and consequently change the translation process. The aim of this study was to access the differences in 3′ UTR variants of SNCA genes in a cohort of PD patients and control subjects from Croatia. The cohort consisted of 52 PD patients and 23 healthy control subjects. Differences between 3′ UTR allele and genotype frequencies were accessed through next generation sequencing approach from whole blood samples. In our study, we identified four previously reported single nucleotide polymorphisms (SNPs) and one insertion in the 3′ UTR region of SNCA gene, namely rs1045722, rs3857053, rs577490090, rs356165, and rs777296100, and five variants not reported in the literature, namely rs35270750, rs529553259, rs377356638, rs571454522, and rs750347645. Our results indicate a significantly higher occurrence of the rs571454522 variant in the PD population. To the best of our knowledge, this variant has not been reported until now in the literature. We analyzed our results in the context of previous research, creating a brief overview of the importance of 3′ UTR variants of the SNCA gene. Further studies will be needed to gain a more profound insight regarding their role in PD development, which will help to assess the role and impact of post-transcriptional regulation on disease pathology.
Brassinosteroids in Plants: Crosstalk with Small-Molecule Compounds
Authors: Hu Dongliang , Wei Lijuan , Liao Weibiao
Published: December 2021

Brassinosteroids (BRs) are known as the sixth type of plant hormone participating in various physiological and biochemical activities and play an irreplaceable role in plants. Small-molecule compounds (SMCs) such as nitric oxide (NO), ethylene, hydrogen peroxide (H2O2), and hydrogen sulfide (H2S) are involved in plant growth and development as signaling messengers. Recently, the involvement of SMCs in BR-mediated growth and stress responses is gradually being discovered in plants, including seed germination, adventitious rooting, stem elongation, fruit ripening, and stress responses. The crosstalk between BRs and SMCs promotes plant development and alleviates stress damage by modulating the antioxidant system, photosynthetic capacity, and carbohydrate metabolism, as well as osmotic adjustment. In the present review, we try to explain the function of BRs and SMCs and their crosstalk in the growth, development, and stress resistance of plants.
Structural and Functional Characterization of Legionella pneumophila Effector MavL
Authors: Voth Kevin , Pasricha Shivani , Chung Ivy Yeuk Wah , Wibawa Rachelia R. , Zainudin Engku Nuraishah Huda E. , Hartland Elizabeth L. , Cygler Miroslaw
Published: December 2021

Legionella pneumophila is a Gram-negative intracellular pathogen that causes Legionnaires’ disease in elderly or immunocompromised individuals. This bacterium relies on the Dot/Icm (Defective in organelle trafficking/Intracellular multiplication) Type IV Secretion System (T4SS) and a large (>330) set of effector proteins to colonize the host cell. The structural variability of these effectors allows them to disrupt many host processes. Herein, we report the crystal structure of MavL to 2.65 Å resolution. MavL adopts an ADP-ribosyltransferase (ART) fold and contains the distinctive ligand-binding cleft of ART proteins. Indeed, MavL binds ADP-ribose with Kd of 13 µM. Structural overlay of MavL with poly-(ADP-ribose) glycohydrolases (PARGs) revealed a pair of aspartate residues in MavL that align with the catalytic glutamates in PARGs. MavL also aligns with ADP-ribose “reader” proteins (proteins that recognize ADP-ribose). Since no glycohydrolase activity was observed when incubated in the presence of ADP-ribosylated PARP1, MavL may play a role as a signaling protein that binds ADP-ribose. An interaction between MavL and the mammalian ubiquitin-conjugating enzyme UBE2Q1 was revealed by yeast two-hybrid and co-immunoprecipitation experiments. This work provides structural and molecular insights to guide biochemical studies aimed at elucidating the function of MavL. Our findings support the notion that ubiquitination and ADP-ribosylation are global modifications exploited by L. pneumophila.
Stimulus-Stimulus-Pairing to Reduce Stereotypies in Three Children with Autism during Movie Watching
Authors: Esposito Marco , Dipierro Maria Teresa , Mondani Federica , Iurato Giulia , Mirizzi Paolo , Mazza Monica , Valenti Marco
Published: December 2021

Autism spectrum disorders represent a challenge for professionals, who must include in their individualized educational interventions goals for core symptoms (social–communication and stereotypies/restricted interests) and comorbidities. The narrowness of interests and the high frequency of repetitive behaviors in children with autism often constitute an obstacle for learning and the quality of life, and for their caregivers as well. In the scientific literature, behavioral interventions based on both aversive and, less commonly, positive procedures have been implemented to reduce the frequency of stereotypies. The following study was carried out with the intention of replicating a Stimulus-Stimulus Pairing procedure applied by Nuzzolo-Gomez, Leonard, Ortiz, Rivera and Greer (2002) in order to reduce stereotypies in children. This procedure was applied to three children diagnosed with autism aged five, almost six and seven years, in order to reduce stereotypies when children watched movies. An A-B-A experimental design with three subjects was used for this research. The results showed a decrease in stereotypies in favor of appropriate behaviors.
The Impact of Temporary Means of Access on Buildings Envelope’s Maintenance Costs
Authors: Ferreira Cláudia , Dias Ilídio S. , Silva Ana , de Brito Jorge , Flores-Colen Inês
Published: December 2021

Accessibility to buildings’ envelope depends on efficient inspection and other maintenance actions of their components. When access to these components is not planned, special means of access are required to carry out the maintenance work. Means of access, besides having a fundamental role on the quality of maintenance works of building envelope components, also represents a considerable part of the maintenance costs. Thus, to optimize costs and resources in maintenance plans, assessment of the impact of the means of access on maintenance costs is crucial. For works in height, there are several alternative means of access. The choice of the most adequate solution is strongly linked to the characteristics (e.g., architecture, height) and constraints (e.g., users, surrounding space) of each building, the maintenance needs of the envelope, and the time and funds available for the intervention. Therefore, in this study, a sensitivity analysis to understand how the cost of means of access can influence the maintenance costs is carried out. Moreover, the optimisation of maintenance activities in façade claddings is also analysed. This study intends to assess whether it is advantageous to consider permanent means of access during the design phase or opt for temporary means of access. In a first stage, the impact of six temporary means of access (supported and suspended scaffolds; articulated booms; telescopic booms; scissor lifts; and rope access) on the maintenance plans developed for the six types of claddings (ceramic tiling systems—CTS, natural stone claddings—NSC, rendered façades—RF, painted surfaces—PS, external thermal insulation composite systems—ETICS, and architectural concrete façades—ACF) is examined. The impact is estimated through a stochastic maintenance model based on Petri nets. After that, a sensitivity analysis and a multi-criteria decision analysis are performed. Based on the results, general recommendations are presented concerning the maintenance strategies to adopt in the cladding solutions analysed. The results reveal that planning the means of access during the design stage can be economically beneficial for all buildings’ envelope components.
PPM1D Is a Therapeutic Target in Childhood Neural Tumors
Authors: Milosevic Jelena , Treis Diana , Fransson Susanne , Gallo-Oller Gabriel , Sveinbjörnsson Baldur , Eissler Nina , Tanino Keiji , Sakaguchi Kazuyasu , Martinsson Tommy , Wickström Malin , Kogner Per , Johnsen John Inge
Published: December 2021

Childhood medulloblastoma and high-risk neuroblastoma frequently present with segmental gain of chromosome 17q corresponding to aggressive tumors and poor patient prognosis. Located within the 17q-gained chromosomal segments is PPM1D at chromosome 17q23.2. PPM1D encodes a serine/threonine phosphatase, WIP1, that is a negative regulator of p53 activity as well as key proteins involved in cell cycle control, DNA repair and apoptosis. Here, we show that the level of PPM1D expression correlates with chromosome 17q gain in medulloblastoma and neuroblastoma cells, and both medulloblastoma and neuroblastoma cells are highly dependent on PPM1D expression for survival. Comparison of different inhibitors of WIP1 showed that SL-176 was the most potent compound inhibiting medulloblastoma and neuroblastoma growth and had similar or more potent effects on cell survival than the MDM2 inhibitor Nutlin-3 or the p53 activator RITA. SL-176 monotherapy significantly suppressed the growth of established medulloblastoma and neuroblastoma xenografts in nude mice. These results suggest that the development of clinically applicable compounds inhibiting the activity of WIP1 is of importance since PPM1D activating mutations, genetic gain or amplifications and/or overexpression of WIP1 are frequently detected in several different cancers.
Interpretability of a Deep Learning Based Approach for the Classification of Skin Lesions into Main Anatomic Body Sites
Authors: Jaworek-Korjakowska Joanna , Brodzicki Andrzej , Cassidy Bill , Kendrick Connah , Yap Moi Hoon
Published: December 2021

Over the past few decades, different clinical diagnostic algorithms have been proposed to diagnose malignant melanoma in its early stages. Furthermore, the detection of skin moles driven by current deep learning based approaches yields impressive results in the classification of malignant melanoma. However, in all these approaches, the researchers do not take into account the origin of the skin lesion. It has been observed that the specific criteria for in situ and early invasive melanoma highly depend on the anatomic site of the body. To address this problem, we propose a deep learning architecture based framework to classify skin lesions into the three most important anatomic sites, including the face, trunk and extremities, and acral lesions. In this study, we take advantage of pretrained networks, including VGG19, ResNet50, Xception, DenseNet121, and EfficientNetB0, to calculate the features with an adjusted and densely connected classifier. Furthermore, we perform in depth analysis on database, architecture, and result regarding the effectiveness of the proposed framework. Experiments confirm the ability of the developed algorithms to classify skin lesions into the most important anatomical sites with 91.45% overall accuracy for the EfficientNetB0 architecture, which is a state-of-the-art result in this domain.
Liver Transplantation for Unresectable Intrahepatic Cholangiocarcinoma: The Role of Sequencing Genetic Profiling
Authors: Gruttadauria Salvatore , Barbera Floriana , Pagano Duilio , Liotta Rosa , Miraglia Roberto , Barbara Marco , Bavetta Maria Grazia , Cammà Calogero , Petridis Ioannis , Di Carlo Daniele , Conaldi Pier Giulio , Di Francesco Fabrizio
Published: December 2021

Intrahepatic cholangiocarcinoma (iCCA) is a rare and aggressive primary liver tumor, characterized by a range of different clinical manifestations and by increasing incidence and mortality rates even after curative treatment with radical resection. In recent years, growing attention has been devoted to this disease and some evidence supports liver transplantation (LT) as an appropriate treatment for intrahepatic cholangiocarcinoma; evolving work has also provided a framework for better understanding the genetic basis of this cancer. The aim of this study was to provide a clinical description of our series of patients complemented with Next-Generation Sequencing genomic profiling. From 1999 to 2021, 12 patients who underwent LT with either iCCA or a combined hepatocellular and cholangiocellular carcinoma (HCC-iCCA) were included in this study. Mutations were observed in gene activating signaling pathways known to be involved with iCCA tumorigenesis (KRAS/MAPK, P53, PI3K-Akt/mTOR, cAMP, WNT, epigenetic regulation and chromatin remodeling). Among several others, a strong association was observed between the Notch pathway and tumor size (point-biserial rhopb = 0.93). Our results are suggestive of the benefit potentially derived from molecular analysis to improve our diagnostic capabilities and to devise new treatment protocols, and eventually ameliorate long-term survival of patients affected by iCCA or HCC-iCCA.
Evaluation of Response to Immune Checkpoint Inhibitors Using a Radiomics, Lesion-Level Approach
Authors: Song Chorog , Park Hyunjin , Lee Ho Yun , Lee Seunghak , Ahn Joong Hyun , Lee Se-Hoon
Published: December 2021

Conventional methods to determine the response to immune checkpoint inhibitors (ICIs) are limited by the unique responses to an ICI. We performed a radiomics approach for all measurable lesions to identify radiomic variables that could distinguish hyperprogressive disease (HPD) on baseline CT scans and classify a dissociated response (DR). One hundred and ninety-six patients with advanced lung cancer, treated with ICI monotherapy, who underwent at least three CT scans, were retrospectively enrolled. For all 621 measurable lesions, HPDv was determined from baseline CT scans using the tumor growth kinetics (TGK) ratio, and radiomics features were extracted. Multivariable logistic regression analysis of radiomics features was performed to discriminate DR. Radiomics features that significantly discriminated HPDv on baseline CT differed according to organ. Of the 196 patients, 54 (27.6%) had a DR and 142 (72.4%) did not have a DR. Overall survival in the group with a DR was significantly inferior to that in the group without a DR (log rank test, p = 0.04). Our study shows that lesion-level analysis using radiomics features has great potential for discriminating HPDv and understanding heterogeneous tumor progression, including a DR, after ICI treatment.
Pathogen-Induced Epigenetic Modifications in Cancers: Implications for Prevention, Detection and Treatment of Cancers in Africa
Authors: Djomkam Zune Alexandra Lindsey , Olwal Charles Ochieng’ , Tapela Kesego , Owoicho Oloche , Nganyewo Nora Nghochuzie , Lyko Frank , Paemka Lily
Published: December 2021

Cancer is a major public health burden worldwide. Tumor formation is caused by multiple intrinsic and extrinsic factors. Many reports have demonstrated a positive correlation between the burden of infectious pathogens and the occurrence of cancers. However, the mechanistic link between pathogens and cancer development remains largely unclear and is subject to active investigations. Apart from somatic mutations that have been widely linked with various cancers, an appreciable body of knowledge points to alterations of host epigenetic patterns as key triggers for cancer development. Several studies have associated various infectious pathogens with epigenetic modifications. It is therefore plausible to assume that pathogens induce carcinogenesis via alteration of normal host epigenetic patterns. Thus, Africa with its disproportionate burden of infectious pathogens is threatened by a dramatic increase in pathogen-mediated cancers. To curb the potential upsurge of such cancers, a better understanding of the role of tropical pathogens in cancer epigenetics could substantially provide resources to improve cancer management among Africans. Therefore, this review discusses cancer epigenetic studies in Africa and the link between tropical pathogens and cancer burden. In addition, we discuss the potential mechanisms by which pathogens induce cancers and the opportunities and challenges of tropical pathogen-induced epigenetic changes for cancer prevention, detection and management.
MicroRNAs: From Junk RNA to Life Regulators and Their Role in Cardiovascular Disease
Authors: Amodio Federica , Caiazza Martina , Fimiani Fabio , Calabrò Paolo , Limongelli Giuseppe
Published: December 2021

MicroRNAs (miRNAs) are single-stranded small non-coding RNA (18–25 nucleotides) that until a few years ago were considered junk RNA. In the last twenty years, they have acquired more importance thanks to the understanding of their influence on gene expression and their role as negative regulators at post-transcriptional level, influencing the stability of messenger RNA (mRNA). Approximately 5% of the genome encodes miRNAs which are responsible for regulating numerous signaling pathways, cellular processes and cell-to-cell communication. In the cardiovascular system, miRNAs control the functions of various cells, such as cardiomyocytes, endothelial cells, smooth muscle cells and fibroblasts, playing a role in physiological and pathological processes and seeming also related to variations in contractility and hereditary cardiomyopathies. They provide a new perspective on the pathophysiology of disorders such as hypertrophy, fibrosis, arrhythmia, inflammation and atherosclerosis. MiRNAs are differentially expressed in diseased tissue and can be released into the circulation and then detected. MiRNAs have become interesting for the development of new diagnostic and therapeutic tools for various diseases, including heart disease. In this review, the concept of miRNAs and their role in cardiomyopathies will be introduced, focusing on their potential as therapeutic and diagnostic targets (as biomarkers).
‘Oxygen-Consuming Complexes’–Catalytic Effects of Iron–Salen Complexes with Dioxygen
Authors: Rydel-Ciszek Katarzyna , Pacześniak Tomasz , Miłaczewska Anna , Chmielarz Paweł , Sobkowiak Andrzej
Published: December 2021

[(salen)FeIII]+MeCN complex is a useful catalyst for cyclohexene oxidation with dioxygen. As the main products, ketone and alcohol are formed. In acetonitrile, [(salen)FeII]MeCN is rapidly oxidized by dioxygen, forming iron(III) species. Voltammetric electroreduction of the [(salen)FeIII]+MeCN complex in the presence of dioxygen causes the increase in current observed, which indicates the existence of a catalytic effect. Further transformations of the oxygen-activated iron(III) salen complex generate an effective catalyst. Based on the catalytic and electrochemical results, as well as DFT calculations, possible forms of active species in c-C6H10 oxidation have been proposed.
Protein Modifications: From Chemoselective Probes to Novel Biocatalysts
Authors: Pessatti Tomás , Terenzi Hernán , Bertoldo Jean
Published: December 2021

Chemical reactions can be performed to covalently modify specific residues in proteins. When applied to native enzymes, these chemical modifications can greatly expand the available set of building blocks for the development of biocatalysts. Nucleophilic canonical amino acid sidechains are the most readily accessible targets for such endeavors. A rich history of attempts to design enhanced or novel enzymes, from various protein scaffolds, has paved the way for a rapidly developing field with growing scientific, industrial, and biomedical applications. A major challenge is to devise reactions that are compatible with native proteins and can selectively modify specific residues. Cysteine, lysine, N-terminus, and carboxylate residues comprise the most widespread naturally occurring targets for enzyme modifications. In this review, chemical methods for selective modification of enzymes will be discussed, alongside with examples of reported applications. We aim to highlight the potential of such strategies to enhance enzyme function and create novel semisynthetic biocatalysts, as well as provide a perspective in a fast-evolving topic.
Single-Atom Catalysts: A Review of Synthesis Strategies and Their Potential for Biofuel Production
Authors: Asikin-Mijan Nurul , Mohd Sidek Haslinda , AlSultan Abdulkareem G. , Azman Nurul Ahtirah , Adzahar Nur Athirah , Ong Hwai Chyuan
Published: December 2021

Biofuels have been derived from various feedstocks by using thermochemical or biochemical procedures. In order to synthesise liquid and gas biofuel efficiently, single-atom catalysts (SACs) and single-atom alloys (SAAs) have been used in the reaction to promote it. SACs are made up of single metal atoms that are anchored or confined to a suitable support to keep them stable, while SAAs are materials generated by bi- and multi-metallic complexes, where one of these metals is atomically distributed in such a material. The structure of SACs and SAAs influences their catalytic performance. The challenge to practically using SACs in biofuel production is to design SACs and SAAs that are stable and able to operate efficiently during reaction. Hence, the present study reviews the system and configuration of SACs and SAAs, stabilisation strategies such as mutual metal support interaction and geometric coordination, and the synthesis strategies. This paper aims to provide useful and informative knowledge about the current synthesis strategies of SACs and SAAs for future development in the field of biofuel production.
Low-Temperature Esterification to Produce Oleic Acid-Based Wax Esters Catalyzed by 4-Dodecylbenzenesulfonic Acid
Authors: Li Zhenzhen , Liu Wei , Yang Guolong
Published: December 2021

Synthesized oleic acid-based wax esters (e.g., cetyl oleate), which can replace spermaceti oil or jojoba oil, have been widely used in the cosmetic, pharmaceutical and other industries. In this work, 4-dodecylbenzenesulfonic acid (DBSA) has been successfully used as an efficient catalyst to synthesize oleic acid-based wax esters through esterification at 40 °C under solvent-free conditions. A 93.6% conversion rate of cetyl alcohol was obtained under optimal conditions: 10 mol% DBSA, a molar ratio of 1.3:1 oleic acid to alcohol, a reaction temperature 40 °C and a reaction time of 4 h. The effect of water content on esterification was investigated, and it was found that the inhibitory effect of water decreased significantly with increasing temperature. Moreover, DBSA-catalyzed esterification could be applied in the production of various oleic acid-based wax esters and excellent conversion (>90%) to esters was obtained under such mild conditions. DBSA-catalyzed low-temperature esterification is an efficient method for the production of liquid wax esters.
Novel Structured Catalytic Reactors
Authors: Landi Gianluca
Published: December 2021

Structured catalytic reactors are widely used in the automotive sector for exhaust after-treatment, thus representing the state-of-art technology in this sector [...]
Molecular Mediators of RNA Loading into Extracellular Vesicles
Authors: Corrado Chiara , Barreca Maria Magdalena , Zichittella Chiara , Alessandro Riccardo , Conigliaro Alice
Published: December 2021

In the last decade, an increasing number of studies have demonstrated that non-coding RNA (ncRNAs) cooperate in the gene regulatory networks with other biomolecules, including coding RNAs, DNAs and proteins. Among them, microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) are involved in transcriptional and translation regulation at different levels. Intriguingly, ncRNAs can be packed in vesicles, released in the extracellular space, and finally internalized by receiving cells, thus affecting gene expression also at distance. This review focuses on the mechanisms through which the ncRNAs can be selectively packaged into extracellular vesicles (EVs).
Co-Expression of Nogo-A in Dopaminergic Neurons of the Human Substantia Nigra Pars Compacta Is Reduced in Parkinson’s Disease
Authors: Eyer Gian-Carlo , Di Santo Stefano , Hewer Ekkehard , Andereggen Lukas , Seiler Stefanie , Widmer Hans Rudolf
Published: December 2021

Parkinson’s disease is mainly characterized by a progressive loss of dopaminergic neurons in the substantia nigra pars compacta. Together with the small number, the high vulnerability of the dopaminergic neurons is a major pathogenic culprit of Parkinson’s disease. Our previous findings of a higher survival of dopaminergic neurons in the substantia nigra co-expressing Nogo-A in an animal model of Parkinson’s disease suggested that Nogo-A may be associated with dopaminergic neurons resilience against Parkinson’s disease neurodegeneration. In the present study, we have addressed the expression of Nogo-A in the dopaminergic neurons in the substantia nigra in postmortem specimens of diseased and non-diseased subjects of different ages. For this purpose, in a collaborative effort we developed a tissue micro array (TMA) that allows for simultaneous staining of many samples in a single run. Interestingly, and in contrast to the observations gathered during normal aging and in the animal model of Parkinson’s disease, increasing age was significantly associated with a lower co-expression of Nogo-A in nigral dopaminergic neurons of patients with Parkinson’s disease. In sum, while Nogo-A expression in dopaminergic neurons is higher with increasing age, the opposite is the case in Parkinson’s disease. These observations suggest that Nogo-A might play a substantial role in the vulnerability of dopaminergic neurons in Parkinson’s disease.
MicroRNA Cues from Nature: A Roadmap to Decipher and Combat Challenges in Human Health and Disease?
Authors: Singh Gurjit , Storey Kenneth B.
Published: December 2021

MicroRNAs are small non-coding RNA (18–24 nt long) that fine-tune gene expression at the post-transcriptional level. With the advent of “multi-omics” analysis and sequencing approaches, they have now been implicated in every facet of basic molecular networks, including metabolism, homeostasis, and cell survival to aid cellular machinery in adapting to changing environmental cues. Many animals must endure harsh environmental conditions in nature, including cold/freezing temperatures, oxygen limitation (anoxia/hypoxia), and food or water scarcity, often requiring them to revamp their metabolic organization, frequently on a seasonal or life stage basis. MicroRNAs are important regulatory molecules in such processes, just as they are now well-known to be involved in many human responses to stress or disease. The present review outlines the role of miRNAs in natural animal models of environmental stress and adaptation including torpor/hibernation, anoxia/hypoxia tolerance, and freeze tolerance. We also discuss putative medical applications of advances in miRNA biology including organ preservation for transplant, inflammation, ageing, metabolic disorders (e.g., obesity), mitochondrial dysfunction (mitoMirs) as well as specialized miRNA subgroups respective to low temperature (CryomiRs) and low oxygen (OxymiRs). The review also covers differential regulation of conserved and novel miRNAs involved at cell, tissue, and stress specific levels across multiple species and their roles in survival. Ultimately, the species-specific comparison and conserved miRNA responses seen in evolutionarily disparate animal species can help us to understand the complex miRNA network involved in regulating and reorganizing metabolism to achieve diverse outcomes, not just in nature, but in human health and disease.
An Optimized Multilayer Perceptrons Model Using Grey Wolf Optimizer to Predict Mechanical and Microstructural Properties of Friction Stir Processed Aluminum Alloy Reinforced by Nanoparticles
Authors: Khoshaim Ahmed B. , Moustafa Essam B. , Bafakeeh Omar Talal , Elsheikh Ammar H.
Published: December 2021

In the current investigation, AA2024 aluminum alloy is reinforced by alumina nanoparticles using a friction stir process (FSP) with multiple passes. The mechanical properties and microstructure observation are conducted experimentally using tensile, microhardness, and microscopy analysis methods. The impacts of the process parameters on the output responses, such as mechanical properties and microstructure grain refinement, were investigated. The effect of multiple FSP passes on the grain refinement, and various mechanical properties are evaluated, then the results are conducted to train a hybrid artificial intelligence predictive model. The model consists of a multilayer perceptrons optimized by a grey wolf optimizer to predict mechanical and microstructural properties of friction stir processed aluminum alloy reinforced by alumina nanoparticles. The inputs of the model were rotational speed, linear processing speed, and number of passes; while the outputs were grain size, aspect ratio, microhardness, and ultimate tensile strength. The prediction accuracy of the developed hybrid model was compared with that of standalone multilayer perceptrons model using different error measures. The developed hybrid model shows a higher accuracy compared with the standalone model.
Thermal Shock Behavior and Particle Erosion Resistance of Toughened GZ Coatings Prepared by Atmospheric Plasma Spraying
Authors: Yang Zining , Wang Weize , Deng Shujuan , Fang Huanjie , Yang Ting , Wang Lubin
Published: December 2021

Gadolinium zirconate with excellent high-temperature phase stability and sintering resistance has become a very promising candidate material for a new generation of thermal barrier coatings (TBCs). However, the low fracture toughness of gadolinium zirconate greatly limits its application. In this study, gadolinium zirconate (GZ) and two kinds of toughened gadolinium zirconate (GZ/YSZ prepared by mixed powder of Gd2Zr2O7 and YSZ and GSZC prepared by (Gd0.925Sc0.075)2(Zr0.7Ce0.3)2O7 powder) double-layered TBCs were prepared by atmospheric plasma spraying (APS). The fracture toughness of the GZ/YSZ coating and GSZC coating were 9 times and 3.5 times that of GZ coating, respectively. The results of thermal shock test showed that the three TBCs exhibit different failure mechanisms. During the thermal shock test, cracking occurred at the interfaces between the YSZ layer and the BC or GZ/YSZ layer, while GSZC TBC failed due to premature cracking inside the GSZC layer. The particle erosion rate of the GZ, GZ/YSZ, and GZSC coatings were 1.81, 0.48, and 1.01 mg/g, respectively, indicating that the erosion resistance of coatings is related to their fracture toughness. Furthermore, the superior erosion resistance of the GZ/YSZ and GSZC coatings can be attributed to the conversion of crack propagation path during the erosion test.
Enhancing Electrical Conductivity and Corrosion Resistance of CrN Coating by Pt Addition
Authors: Wu Hulin , Wang Yihe , Xiang Lin , Song Guanlin , Xie Zhiwen
Published: December 2021

Transition-metal nitride coating used to protect the electronic connector devices in marine environment is required to have high electrical conductivity and good corrosion resistance. This study synthesized a novel CrN–Pt coating with a dense growth texture. Pt addition induced a pronounced increase in electrical conductivity and corrosion resistance. The resistivity decreased from 0.0149 Ohm·cm in the CrN coating to 0.000472 Ohm·cm in the CrN–Pt coating, while the corrosion current density decreased from 24 nA/cm2 in the CrN coating to 6.3 nA/cm2 in the CrN–Pt coating. The results of the above studies confirm that Pt doping has significant advantages in improving the electrical conductivity and corrosion resistance of nitride coatings for potential applications in the marine environment.
Click Fraud in Digital Advertising: A Comprehensive Survey
Authors: Sadeghpour Shadi , Vlajic Natalija
Published: December 2021

Recent research has revealed an alarming prevalence of click fraud in online advertising systems. In this article, we present a comprehensive study on the usage and impact of bots in performing click fraud in the realm of digital advertising. Specifically, we first provide an in-depth investigation of different known categories of Web-bots along with their malicious activities and associated threats. We then ask a series of questions to distinguish between the important behavioral characteristics of bots versus humans in conducting click fraud within modern-day ad platforms. Subsequently, we provide an overview of the current detection and threat mitigation strategies pertaining to click fraud as discussed in the literature, and we categorize the surveyed techniques based on which specific actors within a digital advertising system are most likely to deploy them. We also offer insights into some of the best-known real-world click bots and their respective ad fraud campaigns observed to date. According to our knowledge, this paper is the most comprehensive research study of its kind, as it examines the problem of click fraud both from a theoretical as well as practical perspective.
A Scalable Prototype by In Situ Polymerization of Biodegradables, Cross-Linked Molecular Mode of Vapor Transport, and Metal Ion Rejection for Solar-Driven Seawater Desalination
Authors: Wei Zhou , Arshad Naila , Irshad Muhammad Sultan , Idrees Muhammad , Ahmed Iftikhar , Li Hongrong , Qazi Hummad Habib , Yousaf Muhammad , Alshahrani Lina Abdullah , Lu Yuzheng
Published: December 2021

Water scarcity in mass populated areas has become a major global threat to the survival and sustainability of community life on earth, which needs the prompt attention of technological leadership. Solar evaporation has emerged as a renewable energy resource and a novel technique for clean water production and wastewater treatment. Indeed, mounting a scalable solar evaporator including high evaporation efficiency and thermal management remains a significant challenge. Herein, we demonstrate a self-floatable, ecofriendly polypyrrole/wood sponge-based (PPy@WS) steam generator. The low-cost and easy to fabricate evaporator system consists of a single-step in situ polymerization of a 2-D (two-dimensional) hydrophilic wood sponge abundantly available for commercialization. The as-prepared PPy@WS solar evaporator exhibits excellent wettability and is super hydrophilic (contact angle ∼ 0), salt-resistant, and has an excellent light absorption of ∼94% due to omnidirectional diffusion reflection in PPy Nanoparticles (NPs). The capacity of the PPy@WS evaporator to absorb broadband solar radiation and convert it into thermal energy has enabled it to achieve excellent surface temperature (38.6 °C). The accumulated heat can generate vapors at the rate of 1.62 kg·m−2·h−1 along with 93% photothermal conversion efficiency under one sun (1 kW·m−2). Moreover, the presented prototype possesses the capability to be installed directly without the use of any complex protocol to purify seawater or sewage with an efficient rejection ratio of primary metal ions present in seawater (approximately 100%). This simple fabrication process with renewable polymer resources and photothermal materials can serve as a practical model towards high-performance solar evaporation technology for water-stressed communities in remote areas.
Changes in Brain Energy and Membrane Metabolism in Glioblastoma following Chemoradiation
Authors: Grams Astrid Ellen , Mangesius Stephanie , Steiger Ruth , Radovic Ivan , Rietzler Andreas , Walchhofer Lisa Maria , Galijašević Malik , Mangesius Julian , Nowosielski Martha , Freyschlag Christian Franz , Kerschbaumer Johannes , Gizewski Elke Ruth
Published: December 2021

Brain parenchyma infiltration with glioblastoma (GB) cannot be entirely visualized by conventional magnetic resonance imaging (MRI). The aim of this study was to investigate changes in the energy and membrane metabolism measured with phosphorous MR spectroscopy (31P-MRS) in the presumably “normal-appearing” brain following chemoradiation therapy (CRT) in GB patients in comparison to healthy controls. Twenty (seven female, thirteen male) GB patients underwent a 31P-MRS scan prior to surgery (baseline) and after three months of standard CRT (follow-up examination. The regions of interest “contrast-enhancing (CE) tumor” (if present), “adjacent to the (former) tumor”, “ipsilateral distant” hemisphere, and “contralateral” hemisphere were compared, differentiating between patients with stable (SD) and progressive disease (PD). Metabolite ratios PCr/ATP, Pi/ATP, PCr/Pi, PME/PDE, PME/PCr, and PDE/ATP were investigated. In PD, energy and membrane metabolism in CE tumor areas have a tendency to “normalize” under therapy. In different “normal-appearing” brain areas of GB patients, the energy and membrane metabolism either “normalized” or were “disturbed”, in comparison to baseline or controls. Differences were also detected between patients with SD and PD. 31P-MRS might contribute as an additional imaging biomarker for outcome measurement, which remains to be investigated in a larger cohort.
Changes in Blood Potassium after Reperfusion during Living-Donor Liver Transplantation: An Exploratory Study
Authors: Kim Jeayoun , Kwon Ji-Hye , Kim Gaab Soo
Published: December 2021

The incidence of hyperkalemia (>5.5 mEq/L) or high blood potassium (5–5.5 mEq/L) during living-donor liver transplantation (LDLT) is reported to be more than 10%. It occurs more frequently in the early post-reperfusion period and is a major cause of post-reperfusion arrhythmia and cardiac arrest. Unlike deceased-donor liver transplantation, the pattern of blood potassium changes immediately after reperfusion has not been described in LDLT. From January 2021 to March 2021, fifteen consecutive patients were enrolled. Baseline blood potassium was measured from blood samples obtained 10-min (T-10) and immediately before (T0) reperfusion. During the first 5 min after reperfusion, blood potassium measurements were conducted every one minute (T1–T5). The blood potassium levels at T-10 and T0 were 3.8 ± 0.4 and 3.9 ± 0.4 mEq/L, respectively. After reperfusion, mean increases (95% CI) in blood potassium from T-10 and T0 were 0.5 (0.4–0.6) and 0.4 (0.3–0.5) mEq/L, respectively. Blood potassium peaked at T1, returned to baseline at T3, and fell below the baseline at T5. Peak blood potassium after reperfusion showed strong correlations with blood potassium measured at T-10 (p < 0.001) and T0 (p < 0.0001). These findings can support the establishment of future research plans and perioperative management of blood potassium in LDLT.
Multicenter Evaluation of Rapid BACpro® II for the Accurate Identification of Microorganisms Directly from Blood Cultures Using MALDI-TOF MS
Authors: Oviaño Marina , Ingebretsen André , Steffensen Anne K. , Croxatto Antony , Prod’hom Guy , Quiroga Lidia , Bou Germán , Greub Gilbert , Rodríguez-Temporal David , Rodríguez-Sánchez Belén
Published: December 2021

The identification of microorganisms directly from blood cultures using MALDI-TOF MS has been shown to be the most impacting application of this methodology. In this study, a novel commercial method was evaluated in four clinical microbiology laboratories. Positive blood culture samples (n = 801) were processed using a rapid BACpro® II kit and then compared with the routine gold standard. A subset of monomicrobial BCs (n = 560) were analyzed in parallel with a Sepsityper® Kit (Bruker Daltonics, Bremen, Germany) and compared with the rapid BACpro® II kit. In addition, this kit was also compared with two different in-house methods. Overall, 80.0% of the monomicrobial isolates (609/761; 95% CI 71.5–88.5) were correctly identified by the rapid BACpro® II kit at the species level (92.3% of the Gram negative and 72.4% of the Gram positive bacteria). The comparison with the Sepsityper® Kit showed that the rapid BACpro® II kit generated higher rates of correct species-level identification for all categories (p > 0.0001), except for yeasts identified with score values > 1.7. It also proved superior to the ammonium chloride method (p > 0.0001), but the differential centrifugation method allowed for higher rates of correct identification for Gram negative bacteria (p > 0.1). The percentage of accurate species-level identification of Gram positive bacteria was particularly noteworthy in comparison with other commercial and in-house methods.
Entropy-Based Temporal Downscaling of Precipitation as Tool for Sediment Delivery Ratio Assessment
Authors: Alencar Pedro Henrique Lima , Paton Eva Nora , de Araújo José Carlos
Published: December 2021

Many regions around the globe are subjected to precipitation-data scarcity that often hinders the capacity of hydrological modeling. The entropy theory and the principle of maximum entropy can help hydrologists to extract useful information from the scarce data available. In this work, we propose a new method to assess sub-daily precipitation features such as duration and intensity based on daily precipitation using the principle of maximum entropy. Particularly in arid and semiarid regions, such sub-daily features are of central importance for modeling sediment transport and deposition. The obtained features were used as input to the SYPoME model (sediment yield using the principle of maximum entropy). The combined method was implemented in seven catchments in Northeast Brazil with drainage areas ranging from 10−3 to 10+2 km2 in assessing sediment yield and delivery ratio. The results show significant improvement when compared with conventional deterministic modeling, with Nash–Sutcliffe efficiency (NSE) of 0.96 and absolute error of 21% for our method against NSE of −4.49 and absolute error of 105% for the deterministic approach.
The BioS4You European Project: An Innovative Way to Effectively Engage Z-Generation Students in STEM Disciplines
Authors: Persano Adorno Dominique , Mallahnia Tahereh , Koch Volker , Zailskaitė-Jakštė Ligita , Ostreika Armantas , Urbaitytė Aušra , Punys Vytenis , Pizzolato Nicola
Published: December 2021

In this contribution, we present the BioS4You project and analyse the results obtained in the first 18 months of its activity. The “Bio-Inspired STEM topics for engaging young generations” (BioS4You) Erasmus+ KA2 Innovation project aims to bridge the gap between STEM national curricula (which include Science, Technology, Engineering, and Mathematics) and the needs of Z-generation students, uninterested to basic themes, but enthusiastic in issues related to environmental, social, and health concerns. The BioS4You project engages young learners in STEM subjects, starting with current issues of interest for them, as the social and environmental impact of new technologies, connecting STEM concepts to real-world technologies that are supporting on facing environmental, social, and health current challenges. Novel fields such as Bioengineering, Bioscience, Biotechnology can be implemented into classroom teaching, integrating academic disciplines, and stimulating the academic and social growth of young people. The knowledge of new STEM contents makes the students feel an active part of the technological innovation (and not just passive users) and help them to build a better future, bringing them closer to the STEM world and enabling them to make more informed choices for their future careers.