bluuebunny/crossref_metadata_2025 huggingface dataset:
Dual Roles of Microglia in the Basal Ganglia in Parkinson’s Disease
Authors: Choudhury Mohammed E. , Kigami Yuka , Tanaka Junya
Published: April 2021

With the increasing age of the population, the incidence of Parkinson’s disease (PD) has increased exponentially. The development of novel therapeutic interventions requires an understanding of the involvement of senescent brain cells in the pathogenesis of PD. In this review, we highlight the roles played by microglia in the basal ganglia in the pathophysiological processes of PD. In PD, dopaminergic (DAergic) neuronal degeneration in the substantia nigra pars compacta (SNc) activates the microglia, which then promote DAergic neuronal degeneration by releasing potentially neurotoxic factors, including nitric oxide, cytokines, and reactive oxygen species. On the other hand, microglia are also activated in the basal ganglia outputs (the substantia nigra pars reticulata and the globus pallidus) in response to excess glutamate released from hyperactive subthalamic nuclei-derived synapses. The activated microglia then eliminate the hyperactive glutamatergic synapses. Synapse elimination may be the mechanism underlying the compensation that masks the appearance of PD symptoms despite substantial DAergic neuronal loss. Microglial senescence may correlate with their enhanced neurotoxicity in the SNc and the reduced compensatory actions in the basal ganglia outputs. The dual roles of microglia in different basal ganglia regions make it difficult to develop interventions targeting microglia for PD treatment.
The Antipsychotic Risperidone Alters Dihydroceramide and Ceramide Composition and Plasma Membrane Function in Leukocytes In Vitro and In Vivo
Authors: Canfrán-Duque Alberto , Pastor Óscar , García-Seisdedos David , Molina Yessenia L. , Babiy Bohdan , Lerma Milagros , Sánchez-Castellano Carmen , Martínez-Botas Javier , Gómez-Coronado Diego , Lasunción Miguel A. , Cruz-Jentoft Alfonso J. , Busto Rebeca
Published: April 2021

Atypical or second-generation antipsychotics are used in the treatment of psychosis and behavioral problems in older persons with dementia. However, these pharmaceutical drugs are associated with an increased risk of stroke in such patients. In this study, we evaluated the effects of risperidone treatment on phospholipid and sphingolipid composition and lipid raft function in peripheral blood mononuclear cells (PBMCs) of older patients (mean age >88 years). The results showed that the levels of dihydroceramides, very-long-chain ceramides, and lysophosphatidylcholines decreased in PBMCs of the risperidone-treated group compared with untreated controls. These findings were confirmed by in vitro assays using human THP-1 monocytes. The reduction in the levels of very-long-chain ceramides and dihydroceramides could be due to the decrease in the expression of fatty acid elongase 3, as observed in THP-1 monocytes. Moreover, risperidone disrupted lipid raft domains in the plasma membrane of PBMCs. These results indicated that risperidone alters phospholipid and sphingolipid composition and lipid raft domains in PBMCs of older patients, potentially affecting multiple signaling pathways associated with these membrane domains.
Involvement of Smad7 in Inflammatory Diseases of the Gut and Colon Cancer
Authors: Troncone Edoardo , Marafini Irene , Stolfi Carmine , Monteleone Giovanni
Published: April 2021

In physiological conditions, the human intestinal mucosa is massively infiltrated with various subsets of immune cells, the activity of which is tightly regulated by several counter-regulatory factors. One of these factors is transforming growth factor-β1 (TGF-β1), a cytokine produced by multiple cell types and targeting virtually all the intestinal mucosal cells. Binding of TGF-β1 to its receptors triggers Smad2/3 signaling, thus culminating in the attenuation/suppression of immune–inflammatory responses. In patients with Crohn’s disease and patients with ulcerative colitis, the major human inflammatory bowel diseases (IBD), and in mice with IBD-like colitis, there is defective TGF-β1/Smad signaling due to high levels of the intracellular inhibitor Smad7. Pharmacological inhibition of Smad7 restores TGF-β1 function, thereby reducing inflammatory pathways in patients with IBD and colitic mice. On the other hand, transgenic over-expression of Smad7 in T cells exacerbates colitis in various mouse models of IBD. Smad7 is also over-expressed in other inflammatory disorders of the gut, such as refractory celiac disease, necrotizing enterocolitis and cytomegalovirus-induced colitis, even though evidence is still scarce and mainly descriptive. Furthermore, Smad7 has been involved in colon carcinogenesis through complex and heterogeneous mechanisms, and Smad7 polymorphisms could influence cancer prognosis. In this article, we review the data about the expression and role of Smad7 in intestinal inflammation and cancer.
Antibacterial and Antibiofilm Activities of Novel Antimicrobial Peptides against Multidrug-Resistant Enterotoxigenic Escherichia Coli
Authors: Wu Kang-Chi , Hua Kuo-Feng , Yu Yu-Hsiang , Cheng Yeong-Hsiang , Cheng Ting-Ting , Huang Yao-Kuan , Chang Hui-Wen , Chen Wei-Jung
Published: April 2021

Post-weaning diarrhea due to enterotoxigenic Escherichia coli (ETEC) is a common disease of piglets and causes great economic loss for the swine industry. Over the past few decades, decreasing effectiveness of conventional antibiotics has caused serious problems because of the growing emergence of multidrug-resistant (MDR) pathogens. Various studies have indicated that antimicrobial peptides (AMPs) have potential to serve as an alternative to antibiotics owing to rapid killing action and highly selective toxicity. Our previous studies have shown that AMP GW-Q4 and its derivatives possess effective antibacterial activities against the Gram-negative bacteria. Hence, in the current study, we evaluated the antibacterial efficacy of GW-Q4 and its derivatives against MDR ETEC and their minimal inhibition concentration (MIC) values were determined to be around 2~32 μg/mL. Among them, AMP Q4-15a-1 with the second lowest MIC (4 μg/mL) and the highest minimal hemolysis concentration (MHC, 256 μg/mL), thus showing the greatest selectivity (MHC/MIC = 64) was selected for further investigations. Moreover, Q4-15a-1 showed dose-dependent bactericidal activity against MDR ETEC in time–kill curve assays. According to the cellular localization and membrane integrity analyses using confocal microscopy, Q4-15a-1 can rapidly interact with the bacterial surface, disrupt the membrane and enter cytosol in less than 30 min. Minimum biofilm eradication concentration (MBEC) of Q4-15a-1 is 4× MIC (16 μg/mL), indicating that Q4-15a-1 is effective against MDR ETEC biofilm. Besides, we established an MDR ETEC infection model with intestinal porcine epithelial cell-1 (IPEC-1). In this infection model, 32 μg/mL Q4-15a-1 can completely inhibit ETEC adhesion onto IPEC-1. Overall, these results suggested that Q4-15a-1 may be a promising antibacterial candidate for treatment of weaned piglets infected by MDR ETEC.
PEA-OXA Mitigates Oxaliplatin-Induced Painful Neuropathy through NF-κB/Nrf-2 Axis
Authors: Campolo Michela , Lanza Marika , Paterniti Irene , Filippone Alessia , Ardizzone Alessio , Casili Giovanna , Scuderi Sarah A. , Puglisi Caterina , Mare Marzia , Memeo Lorenzo , Cuzzocrea Salvatore , Esposito Emanuela
Published: April 2021

Chemotherapy-induced neuropathy is a common, dose-dependent adverse effect of several antineoplastics, such as oxaliplatin (L-OHP). The aim of the present work was to evaluate the potential beneficial effects of 2-pentadecyl-2-oxazoline (PEA-OXA) in a murine model of oxaliplatin-induced peripheral neuropathy (OIPN). OIPN was induced by an intraperitoneally injection of L-OHP in rats on five consecutive days (D0–4) for a final cumulative dose of 10 mg/kg. PEA-OXA and ultramicronized palmitoylethanolamide (PEAum), both 10 mg/kg, were given orally 15–20 min prior (L-OHP) and sacrifice was made on day 25. Our results demonstrated that PEA-OXA, more than PEAum, reduced the development of hypersensitivity in rats; this was associated with the reduction in hyperactivation of glia cells and the increased production of proinflammatory cytokines in the dorsal horn of the spinal cord, accompanied by an upregulation of neurotrophic factors in the dorsal root ganglia (DRG). Moreover, we showed that PEA-OXA reduced L-OHP damage via a reduction in NF-κB pathway activation and a modulation of Nrf-2 pathways. Our findings identify PEA-OXA as a therapeutic target in chemotherapy-induced painful neuropathy, through the biomolecular signaling NF-κB/Nrf-2 axis, thanks to its abilities to counteract L-OHP damage. Therefore, we can consider PEA-OXA as a promising adjunct to chemotherapy to reduce chronic pain in patients.
Identification of Potential Leukocyte Biomarkers Related to Drug Recovery of CFTR: Clinical Applications in Cystic Fibrosis
Authors: Pedrazzi Marco , Vercellone Silvia , Barberis Elettra , Capraro Michela , De Tullio Roberta , Cresta Federico , Casciaro Rosaria , Castellani Carlo , Patrone Mauro , Marengo Emilio , Lecca Paola , Melotti Paola , Sorio Claudio , Manfredi Marcello , Averna Monica
Published: April 2021

The aim of this study was the identification of specific proteomic profiles, related to a restored cystic fibrosis transmembrane conductance regulator (CFTR) activity in cystic fibrosis (CF) leukocytes before and after ex vivo treatment with the potentiator VX770. We used leukocytes, isolated from CF patients carrying residual function mutations and eligible for Ivacaftor therapy, and performed CFTR activity together with proteomic analyses through micro-LC–MS. Bioinformatic analyses of the results obtained revealed the downregulation of proteins belonging to the leukocyte transendothelial migration and regulation of actin cytoskeleton pathways when CFTR activity was rescued by VX770 treatment. In particular, we focused our attention on matrix metalloproteinase 9 (MMP9), because the high expression of this protease potentially contributes to parenchyma lung destruction and dysfunction in CF. Thus, the downregulation of MMP9 could represent one of the possible positive effects of VX770 in decreasing the disease progression, and a potential biomarker for the prediction of the efficacy of therapies targeting the defect of Cl− transport in CF.
Low Light/Darkness as Stressors of Multifactor-Induced Senescence in Rice Plants
Authors: Gad Ahmed G. , Habiba  , Zheng Xiangzi , Miao Ying
Published: April 2021

Leaf senescence, as an integral part of the final development stage for plants, primarily remobilizes nutrients from the sources to the sinks in response to different stressors. The premature senescence of leaves is a critical challenge that causes significant economic losses in terms of crop yields. Although low light causes losses of up to 50% and affects rice yield and quality, its regulatory mechanisms remain poorly elucidated. Darkness-mediated premature leaf senescence is a well-studied stressor. It initiates the expression of senescence-associated genes (SAGs), which have been implicated in chlorophyll breakdown and degradation. The molecular and biochemical regulatory mechanisms of premature leaf senescence show significant levels of redundant biomass in complex pathways. Thus, clarifying the regulatory mechanisms of low-light/dark-induced senescence may be conducive to developing strategies for rice crop improvement. This review describes the recent molecular regulatory mechanisms associated with low-light response and dark-induced senescence (DIS), and their effects on plastid signaling and photosynthesis-mediated processes, chloroplast and protein degradation, as well as hormonal and transcriptional regulation in rice.
Effect of Central Corticotropin-Releasing Factor on Hepatic Lipid Metabolism and Inflammation-Related Gene Expression in Rats
Authors: Nakade Yukiomi , Kitano Rena , Yamauchi Taeko , Kimoto Satoshi , Sakamoto Kazumasa , Inoue Tadahisa , Kobayashi Yuji , Ohashi Tomohiko , Sumida Yoshio , Ito Kiyoaki , Yoneda Masashi
Published: April 2021

Corticotropin-releasing factor (CRF) in the brain acts on physiological and pathophysiological modulation of the hepatobiliary system. Central CRF administration aggravates experimental acute liver injury by decreasing hepatic blood flow. Conversely, minimal evidence is available regarding the effect of centrally acting CRF on hepatic lipid metabolism and inflammation. We examined whether central CRF affects hepatic lipid metabolism and inflammation-related gene expression in rats. Male Long Evans rats were intracisternally injected with CRF (10 μg) or saline. Rats were sacrificed 2 h, 6 h, and 24 h after the CRF injection, the liver was isolated, and mRNA was extracted. Next, hepatic lipid metabolism and inflammation-related gene expression were examined. Hepatic SREBF1 (sterol regulatory element-binding transcription factor 1) mRNA levels were significantly increased 6 h and 24 h after intracisternal CRF administration when compared with those in the control group. Hepatic TNFα and IL1β mRNA levels increased significantly 6 h after intracisternal CRF administration. Hepatic sympathectomy or guanethidine treatment, not hepatic branch vagotomy or atropine treatment, inhibited central CRF-induced increase in hepatic SREBF1, TNFα and IL1β mRNA levels. These results indicated that central CRF affects hepatic de novo lipogenesis and inflammation-related gene expression through the sympathetic-noradrenergic nervous system in rats.
Human Endogenous Retrovirus (HERV)-K env Gene Knockout Affects Tumorigenic Characteristics of nupr1 Gene in DLD-1 Colorectal Cancer Cells
Authors: Ko Eun-Ji , Ock Mee-Sun , Choi Yung-Hyun , Iovanna Juan L. , Mun Seyoung , Han Kyudong , Kim Heui-Soo , Cha Hee-Jae
Published: April 2021

Human endogenous retroviruses (HERVs) are suggested to be involved in the development of certain diseases, especially cancers. To elucidate the function of HERV-K Env protein in cancers, an HERV-K env gene knockout (KO) in DLD-1 colorectal cancer cell lines was generated using the CRISPR-Cas9 system. Transcriptome analysis of HERV-K env KO cells using next-generation sequencing (NGS) was performed to identify the key genes associated with the function of HERV-K Env protein. The proliferation of HERV-K env KO cells was significantly reduced in in vitro culture as well as in in vivo nude mouse model. Tumorigenic characteristics, including migration, invasion, and tumor colonization, were also significantly reduced in HERV-K env KO cells. Whereas, they were enhanced in HERV-K env over-expressing DLD-1 cells. The expression of nuclear protein-1 (NUPR1), an ER-stress response factor that plays an important role in cell proliferation, migration, and reactive oxygen species (ROS) generation in cancer cells, significantly reduced in HERV-K env KO cells. ROS levels and ROS-related gene expression was also significantly reduced in HERV-K env KO cells. Cells transfected with NUPR1 siRNA (small interfering RNA) exhibited the same phenotype as HERV-K env KO cells. These results suggest that the HERV-K env gene affects tumorigenic characteristics, including cell proliferation, migration, and tumor colonization through NUPR1 related pathway.
Molecular Imaging of Apoptosis: The Case of Caspase-3 Radiotracers
Authors: Beroske Lucas , Van den Wyngaert Tim , Stroobants Sigrid , Van der Veken Pieter , Elvas Filipe
Published: April 2021

The molecular imaging of apoptosis remains an important method for the diagnosis and monitoring of the progression of certain diseases and the evaluation of the efficacy of anticancer apoptosis-inducing therapies. Among the multiple biomarkers involved in apoptosis, activated caspase-3 is an attractive target, as it is the most abundant of the executioner caspases. Nuclear imaging is a good candidate, as it combines a high depth of tissue penetration and high sensitivity, features necessary to detect small changes in levels of apoptosis. However, designing a caspase-3 radiotracer comes with challenges, such as selectivity, cell permeability and transient caspase-3 activation. In this review, we discuss the different caspase-3 radiotracers for the imaging of apoptosis together with the challenges of the translation of various apoptosis-imaging strategies in clinical trials.
Genetic Architecture and Molecular, Imaging and Prodromic Markers in Dementia with Lewy Bodies: State of the Art, Opportunities and Challenges
Authors: Combi Romina , Salsone Maria , Villa Chiara , Ferini-Strambi Luigi
Published: April 2021

Dementia with Lewy bodies (DLB) is one of the most common causes of dementia and belongs to the group of α-synucleinopathies. Due to its clinical overlap with other neurodegenerative disorders and its high clinical heterogeneity, the clinical differential diagnosis of DLB from other similar disorders is often difficult and it is frequently underdiagnosed. Moreover, its genetic etiology has been studied only recently due to the unavailability of large cohorts with a certain diagnosis and shows genetic heterogeneity with a rare contribution of pathogenic mutations and relatively common risk factors. The rapid increase in the reported cases of DLB highlights the need for an easy, efficient and accurate diagnosis of the disease in its initial stages in order to halt or delay the progression. The currently used diagnostic methods proposed by the International DLB consortium rely on a list of criteria that comprises both clinical observations and the use of biomarkers. Herein, we summarize the up-to-now reported knowledge on the genetic architecture of DLB and discuss the use of prodromal biomarkers as well as recent promising candidates from alternative body fluids and new imaging techniques.
Characterization of Two Complete Mitochondrial Genomes of Atkinsoniella (Hemiptera: Cicadellidae: Cicadellinae) and the Phylogenetic Implications
Authors: Jiang Yan , Li Hao-Xi , Yu Xiao-Fei , Yang Mao-Fa
Published: April 2021

The complete mitochondrial genomes of Atkinsoniella grahami and Atkinsoniella xanthonota were sequenced. The results showed that the mitogenomes of these two species are 15,621 and 15,895 bp in length, with A+T contents of 78.6% and 78.4%, respectively. Both mitogenomes contain 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), 2 ribosomal RNA genes (rRNAs), and a control region (CR). For all PCGs, a standard start ATN codon (ATT, ATG, or ATA) was found at the initiation site, except for ATP8, for which translation is initiated with a TTG codon. All PCGs terminate with a complete TAA or TAG stop codon, except for COX2, which terminates with an incomplete stop codon T. All tRNAs have the typical cloverleaf secondary structure, except for trnS, which has a reduced dihydrouridine arm. Furthermore, these phylogenetic analyses were reconstructed based on 13 PCGs and two rRNA genes of 73 mitochondrial genome sequences, with both the maximum likelihood (ML) and Bayesian inference (BI) methods. The obtained mitogenome sequences in this study will promote research into the classification, population genetics, and evolution of Cicadellinae insects in the future.
Safe, Secure and Sustainable Oil and Gas Drilling, Exploitation and Pipeline Transport Offshore
Authors: Brkić Dejan , Praks Pavel
Published: April 2021

The Special Issue “Safe, Secure and Sustainable Oil and Gas Drilling, Exploitation and Pipeline Transport Offshore” was focused on regulations, including technical and operational standards, safety technologies, and organizational factors, which can greatly contribute to the occurrence of accidents in the offshore oil and gas sector [...]
COLREG-Compliant Optimal Path Planning for Real-Time Guidance and Control of Autonomous Ships
Authors: Zaccone Raphael
Published: April 2021

While collisions and groundings still represent the most important source of accidents involving ships, autonomous vessels are a central topic in current research. When dealing with autonomous ships, collision avoidance and compliance with COLREG regulations are major vital points. However, most state-of-the-art literature focuses on offline path optimisation while neglecting many crucial aspects of dealing with real-time applications on vessels. In the framework of the proposed motion-planning, navigation and control architecture, this paper mainly focused on optimal path planning for marine vessels in the perspective of real-time applications. An RRT*-based optimal path-planning algorithm was proposed, and collision avoidance, compliance with COLREG regulations, path feasibility and optimality were discussed in detail. The proposed approach was then implemented and integrated with a guidance and control system. Tests on a high-fidelity simulation platform were carried out to assess the potential benefits brought to autonomous navigation. The tests featured real-time simulation, restricted and open-water navigation and dynamic scenarios with both moving and fixed obstacles.
The Australian Stock Market’s Reaction to the First Wave of the COVID-19 Pandemic and Black Summer Bushfires: A Sectoral Analysis
Authors: Gunay Samet , Bakry Walid , Al-Mohamad Somar
Published: April 2021

In this study, we investigated the impact of the first wave of the COVID-19 pandemic on various sectors of the Australian stock market. Market capitalization and equally weighted indices were formed for eleven Australian sectors to examine the influence of the pandemic on them. First, we examined the financial contagion between the Chinese stock market and Australian sector indices through the dynamic conditional correlation fractionally integrated generalized autoregressive conditional heteroskedasticity (DCC-FIGARCH) model. We found high time-varying correlations between the Chinese stock market and most of the Australian sector indices, with the financial, health care, information technology, and utility sectors displaying a decrease in co-movements during the pandemic. The Modified Iterative Cumulative Sum of Squares (MICSS) analysis results indicated the presence of structural breaks in the volatilities of most of the sector indices around the end of February 2020, but consumer staples, industry, information technology and real estate indices did not display any break. Markov regime-switching regression analysis depicted that the pandemic has mainly affected three sectors: consumer staples, industry, and real estate. When we considered the firm size, we found that smaller companies in the energy sector exhibited gradual deterioration, whereas small firms in the consumer staples sector experienced the largest positive impact from the pandemic.
Coherence of Cadastral Data in Land Management—A Case Study of Rural Areas in Poland
Authors: Kocur-Bera Katarzyna , Frąszczak Hubert
Published: April 2021

The cadaster functions laid down in the law should guarantee the safety of one’s rights. The reliability of the data gathered in the cadaster affects decisions concerning specific real estate or taken within the sphere of economic management. The legislation often requires the use of cadastral data, which makes it necessary to keep it up-to-date and coherent with the situation in the field. The effects of a lack of coherence may impact public finances and land management. Maintaining high-quality cadastral data is time-consuming and expensive. This study analysed the data coherence between the state in the field and cadastral documents. The analysis was based mainly on the information about the area of a plot and land use. The coherence index showed that the differences between registers and the state in the field range from 30% to 80%. This can be changed by comprehensive data modernisation, which can be facilitated using modern technology. Given the diverse use of cadastral data and the global trends in cadaster development and implementation of the third dimension, the currency and reliability of cadastral data become particularly important.
Electromagnetic Interference Shielding Anisotropy of Unidirectional CFRP Composites
Authors: Hong Jun , Xu Ping
Published: April 2021

Carbon fiber-reinforced polymer (CFRP) composites have excellent mechanical properties and electromagnetic interference (EMI) shielding performance. Recently, their EMI shielding performance has also attracted great attention in many industrial fields to resolve electromagnetic pollution. The present paper mainly investigated the EMI shielding anisotropy of CFRP materials using a specified set-up of free-space measurement. The electrical conductivity of unidirectional CFRP composites was identified to vary with the fiber orientation angles, and the formula was proposed to predict the results consistent with the experimental. The obvious EMI shielding anisotropy of unidirectional CFRP composites was clarified by free-space measurement. The theoretical formula can predict the EMI shielding value at different carbon fiber orientation angles, and the predicted results were highly consistent with the experimental results. A comparison of the free-space measurement and the coaxial transmission line method was also conducted, which indicated that special attention should be paid to the influence of the anisotropy of CFRP composites on the shielding results. With those results, the mechanism of EMI shielding anisotropy of CFRP composites is clarified, which will provide an effective design of EMI shielding products with a designable shielding direction and frequency.
Development of a New Finishing Process Combining a Fixed Abrasive Polishing with Magnetic Abrasive Finishing Process
Authors: Zou Yanhua , Satou Ryunosuke , Yamazaki Ozora , Xie Huijun
Published: April 2021

High quality, highly efficient finishing processes are required for finishing difficult-to-machine materials. Magnetic abrasive finishing (MAF) process is a finishing method that can obtain a high accuracy surface using fine magnetic particles and abrasive particles, but has poor finishing efficiency. On the contrary, fixed abrasive polishing (FAP) is a polishing process can obtain high material removal efficiency but often cannot provide a high-quality surface at the nano-scale. Therefore, this work proposes a new finishing process, which combines the magnetic abrasive finishing process and the fixed abrasive polishing process (MAF-FAP). To verify the proposed methodology, a finishing device was developed and finishing experiments on alumina ceramic plates were performed. Furthermore, the mechanism of the MAF-FAP process was investigated. In addition, the influence of process parameters on finishing characteristics is discussed. According to the experimental results, this process can achieve high-efficiency finishing of brittle hard materials (alumina ceramics) and can obtain nano-scale surfaces. The surface roughness of the alumina ceramic plate is improved from 202.11 nm Ra to 3.67 nm Ra within 30 min.
Population Diversity Control of Genetic Algorithm Using a Novel Injection Method for Bankruptcy Prediction Problem
Authors: Al-Milli Nabeel , Hudaib Amjad , Obeid Nadim
Published: April 2021

Exploration and exploitation are the two main concepts of success for searching algorithms. Controlling exploration and exploitation while executing the search algorithm will enhance the overall performance of the searching algorithm. Exploration and exploitation are usually controlled offline by proper settings of parameters that affect the population-based algorithm performance. In this paper, we proposed a dynamic controller for one of the most well-known search algorithms, which is the Genetic Algorithm (GA). Population Diversity Controller-GA (PDC-GA) is proposed as a novel feature-selection algorithm to reduce the search space while building a machine-learning classifier. The PDC-GA is proposed by combining GA with k-mean clustering to control population diversity through the exploration process. An injection method is proposed to redistribute the population once 90% of the solutions are located in one cluster. A real case study of a bankruptcy problem obtained from UCI Machine Learning Repository is used in this paper as a binary classification problem. The obtained results show the ability of the proposed approach to enhance the performance of the machine learning classifiers in the range of 1% to 4%.
Phage Digestion of a Bacterial Capsule Imparts Resistance to Two Antibiotic Agents
Authors: Luo Cheng-Hung , Hsu Ya-Han , Wu Wen-Jui , Chang Kai-Chih , Yeh Chen-Sheng
Published: April 2021

Bacteriophages are viruses that infect bacteria, replicating and multiplying using host resources. For specific infections, bacteriophages have developed extraordinary proteins for recognizing and degrading their host. Inspired by the remarkable development of viral proteins, we used the tail fiber protein to treat multiple drug-resistant Acinetobacter baumannii. The tail fiber protein exhibits polysaccharide depolymerases activity which specifically degrades exopolysaccharide (EPS) during the phage–host interaction. However, EPS-degraded cells are observed altering host susceptibility to bacterial lysis peptide, the endolysin-derived peptide. Notably, endolysin is necessary in the process of progeny liberation by breaking the bacterial cell wall. Surprisingly, peeling the EPS animated host to resist colistin, the last-resort antibiotic used in multidrug-resistant Gram-negative bacteria infection. Tail fiber-modified cell wall reduces colistin attachment, causing temporary antibiotic-resistance and possibly raising clinical risks in treating multiple drug-resistant A. baumannii.
Comparison of Clinical, Laboratory and Immune Characteristics of the Monophasic and Biphasic Course of Tick-Borne Encephalitis
Authors: Bogovič Petra , Lotrič-Furlan Stanka , Avšič-Županc Tatjana , Korva Miša , Kastrin Andrej , Lusa Lara , Strle Klemen , Strle Franc
Published: April 2021

The biphasic course of tick-borne encephalitis (TBE) is well described, but information on the monophasic course is limited. We assessed and compared the clinical presentation, laboratory findings, and immune responses in 705 adult TBE patients: 283 with monophasic and 422 with biphasic course. Patients with the monophasic course were significantly (p ≤ 0.002) older (57 vs. 50 years), more often vaccinated against TBE (7.4% vs. 0.9%), more often had comorbidities (52% vs. 37%), and were more often treated in the intensive care unit (12.4% vs. 5.2%). Multivariate logistic regression found strong association between the monophasic TBE course and previous TBE vaccination (OR = 18.45), presence of underlying illness (OR = 1.85), duration of neurologic involvement before cerebrospinal fluid (CSF) examination (OR = 1.39), and patients’ age (OR = 1.02). Furthermore, patients with monophasic TBE had higher CSF levels of immune mediators associated with innate and adaptive (Th1 and B-cell) immune responses, and they had more pronounced disruption of the blood–brain barrier. However, the long-term outcome 2–7 years after TBE was comparable. In summary, the monophasic course is a frequent and distinct presentation of TBE that is associated with more difficult disease course and higher levels of inflammatory mediators in CSF than the biphasic course; however, the long-term outcome is similar.
Persistence of SARS-CoV-2 Viral RNA in Nasopharyngeal Swabs after Death: An Observational Study
Authors: Servadei Francesca , Mauriello Silvestro , Scimeca Manuel , Caggiano Bartolo , Ciotti Marco , Anemona Lucia , Montanaro Manuela , Giacobbi Erica , Treglia Michele , Bernardini Sergio , Marsella Luigi Tonino , Urbano Nicoletta , Schillaci Orazio , Mauriello Alessandro
Published: April 2021

The aim of this study was to investigate the persistence of SARS-CoV-2 in post-mortem swabs of subjects who died from SARS-CoV-2 infection. The presence of the virus was evaluated post-mortem from airways of 27 SARS-CoV-2 positive patients at three different time points (T1 2 h; T2 12 h; T3 24 h) by real-time PCR. Detection of antibodies to SARS-CoV-2 was performed by Maglumi 2019-nCoV IgM/IgG chemiluminescence assay. SARS-CoV-2 viral RNA was still detectable in 70.3% of cases within 2 h after death and in 66,6% of cases up to 24 h after death. Our data showed an increase of the viral load in 78,6% of positive individuals 24 h post-mortem (T3) in comparison to that evaluated 2 h after death (T1). Noteworthy, we detected a positive T3 post-mortem swab (24 h after death) from 4 subjects who were negative at T1 (2 h after death). The results of our study may have an important value in the management of deceased subjects not only with a suspected or confirmed diagnosis of SARS-CoV-2, but also for unspecified causes and in the absence of clinical documentation or medical assistance.
Candida auris: Epidemiology, Diagnosis, Pathogenesis, Antifungal Susceptibility, and Infection Control Measures to Combat the Spread of Infections in Healthcare Facilities
Authors: Ahmad Suhail , Alfouzan Wadha
Published: April 2021

Candida auris, a recently recognized, often multidrug-resistant yeast, has become a significant fungal pathogen due to its ability to cause invasive infections and outbreaks in healthcare facilities which have been difficult to control and treat. The extraordinary abilities of C. auris to easily contaminate the environment around colonized patients and persist for long periods have recently resulted in major outbreaks in many countries. C. auris resists elimination by robust cleaning and other decontamination procedures, likely due to the formation of ‘dry’ biofilms. Susceptible hospitalized patients, particularly those with multiple comorbidities in intensive care settings, acquire C. auris rather easily from close contact with C. auris-infected patients, their environment, or the equipment used on colonized patients, often with fatal consequences. This review highlights the lessons learned from recent studies on the epidemiology, diagnosis, pathogenesis, susceptibility, and molecular basis of resistance to antifungal drugs and infection control measures to combat the spread of C. auris infections in healthcare facilities. Particular emphasis is given to interventions aiming to prevent new infections in healthcare facilities, including the screening of susceptible patients for colonization; the cleaning and decontamination of the environment, equipment, and colonized patients; and successful approaches to identify and treat infected patients, particularly during outbreaks.
A Tentative Study of the Effects of Heat-Inactivation of the Probiotic Strain Shewanella putrefaciens Pdp11 on Senegalese Sole (Solea senegalensis) Intestinal Microbiota and Immune Response
Authors: Domínguez-Maqueda Marta , Cerezo Isabel , Tapia-Paniagua Silvana , De La Banda Inés , Moreno-Ventas Xabier , Moriñigo Miguel , Balebona Maria
Published: April 2021

Concerns about safety, applicability and functionality associated with live probiotic cells have led to consideration of the use of non-viable microorganisms, known as paraprobiotics. The present study evaluated the effects of dietary administration of heat-inactivated cells of the probiotic strain Shewanella putrefaciens Pdp11 on the intestinal microbiota and immune gene transcription in Solea senegalensis. Results obtained were evaluated and compared to those described after feeding with viable Pdp11 cells. S. senegalensis specimens were fed with basal (control) diet or supplemented with live or heat inactivated (60 °C, 1 h) probiotics diets for 45 days. Growth improvement was observed in the group receiving live probiotics compared to the control group, but not after feeding with a probiotic heat-inactivated diet. Regarding immune gene transcription, no changes were observed for tnfα, il-6, lys-c1, c7, hsp70, and hsp90aa in the intestinal samples based on the diet. On the contrary, hsp90ab, gp96, cd4, cd8, il-1β, and c3 transcription were modulated after probiotic supplementation, though no differences between viable and heat-inactivated probiotic supplemented diets were observed. Modulation of intestinal microbiota showed remarkable differences based on the viability of the probiotics. Thus, higher diversity in fish fed with live probiotic cells, jointly with increased Mycoplasmataceae and Spirochaetaceae to the detriment of Brevinemataceae, was detected. However, microbiota of fish receiving heat-inactivated probiotic cells showed decreased Mycoplasmataceae and increased Brevinemataceae and Vibrio genus abundance. In short, the results obtained indicate that the viable state of Pdp11 probiotic cells affects growth performance and modulation of S. senegalensis intestinal microbiota. On the contrary, minor changes were detected in the intestinal immune response, being similar for fish receiving both, viable and inactivated probiotic cell supplemented diets, when compared to the control diet.
Bacterial Communities Associated with Poa annua Roots in Central European (Poland) and Antarctic Settings (King George Island)
Authors: Znój Anna , Grzesiak Jakub , Gawor Jan , Gromadka Robert , Chwedorzewska Katarzyna J.
Published: April 2021

Poa annua (annual bluegrass) is one of the most ubiquitous grass species in the world. In isolated regions of maritime Antarctica, it has become an invasive organism threatening native tundra communities. In this study, we have explored and compared the rhizosphere and root-endosphere dwelling microbial community of P. annua specimens of maritime Antarctic and Central European origin in terms of bacterial phylogenetic diversity and microbial metabolic activity with a geochemical soil background. Our results show that the rhizospheric bacterial community was unique for each sampling site, yet the endosphere communities were similar to each other. However, key plant-associated bacterial taxa such as the Rhizobiaceae family were poorly represented in Antarctic samples, probably due to high salinity and heavy metal concentrations in the soil. Metabolic activity in the Antarctic material was considerably lower than in Central European samples. Antarctic root endosphere showed unusually high numbers of certain opportunistic bacterial groups, which proliferated due to low competition conditions. Thirteen bacterial families were recognized in this study to form a core microbiome of the P. annua root endosphere. The most numerous were the Flavobacteriaceae, suspected to be major contributors to the ecological success of annual bluegrass, especially in harsh, Antarctic conditions.
Design, Synthesis, and Validation of a Novel [11C]Promethazine PET Probe for Imaging Abeta Using Autoradiography
Authors: Whitmore Clayton A. , Boules Mariam I. , Behof William J. , Haynes Justin R. , Koktysh Dmitry , Rosenberg Adam J. , Tantawy Mohammed N. , Pham Wellington
Published: April 2021

Promethazine, an antihistamine drug used in the clinical treatment of nausea, has been demonstrated the ability to bind Abeta in a transgenic mouse model of Alzheimer’s disease. However, so far, all of the studies were performed in vitro using extracted tissues. In this work, we report the design and synthesis of a novel [11C]promethazine PET radioligand for future in vivo studies. The [11C]promethazine was isolated by RP-HPLC with radiochemical purity >95% and molar activity of 48 TBq/mmol. The specificity of the probe was demonstrated using human hippocampal tissues via autoradiography.
Mesomorphic Behavior of Symmetric Azomethine Dimers Containing Different Chromophore Groups
Authors: Perju Elena , Marin Luminita
Published: April 2021

A series of new azomethine dimers was synthesized by the condensation reaction of flexible bis-benzaldehydes with four aromatic amines containing phenyl, naphthyl, anthracene and pyrene groups. Their right structure was confirmed by FTIR and 1H-NMR spectroscopy and their thermal properties were investigated by thermogravimetric analysis, differential scanning calorimetry and polarized light optical microscopy. A view on their photophysical behavior was gained by UV-vis and photoluminescence spectroscopy. The dimers containing pyrene and anthracene presented liquid crystalline behavior, while the other dimers were crystalline compounds. Two dimers containing pyrene moieties formed mesomorphic glasses and had intense luminescence, promising properties for applications in building optoelectronic devices.
Surface Modification Effect and Electrochemical Performance of LiOH-High Surface Activated Carbon as a Cathode Material in EDLC
Authors: Otgonbayar Zambaga , Yang Sunhye , Kim Ick-Jun , Oh Won-Chun
Published: April 2021

This study aimed to improve the performance of the activated carbon-based cathode by increasing the Li content and to analyze the effect of the combination of carbon and oxidizing agent. The crystal structure and chemical structure phase of Li-high surface area activated carbon material (Li-HSAC) was analyzed by X-ray diffraction (XRD) and Raman spectroscopy, the surface state and quantitative element by scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDX) and the surface properties with pore-size distribution by Brunauer–Emmett–Teller (BET), Barrett–Joyner–Halenda (BJH) and t-plot methods. The specific surface area of the Li-YP80F is 1063.2 m2/g, micropore volume value is 0.511 cm3/g and mesopore volume is 0.143 cm3/g, and these all values are higher than other LiOH-treated carbon. The surface functional group was analyzed by a Boehm titration, and the higher number of acidic groups compared to the target facilitated the improved electrolyte permeability, reduced the interface resistance and increased the electrochemical properties of the cathode. The oxidizing agent of LiOH treated high surface area of activated carbon was used for the cathode material for EDLC (electric double layer capacitor) to determine its electrochemical properties and the as-prepared electrode retained excellent performance after 10 cycles and 100 cycles. The anodic and cathodic peak current value and peak segregation of Li-YP80F were better than those of the other two samples, due to the micropore-size and physical properties of the sample. The oxidation peak current value appeared at 0.0055 mA/cm2 current density and the reduction peak value at –0.0014 mA/cm2, when the Li-YP80F sample used to the Cu-foil surface. The redox peaks appeared at 0.0025 mA/cm2 and –0.0009 mA/cm2, in the case of using a Nickel foil, after 10 cycling test. The electrochemical stability of cathode materials was tested by 100 recycling tests. After 100 recycling tests, peak current drop decreased the peak profile became stable. The LiOH-treated high surface area of activated carbon had synergistically upgraded electrochemical activity and superior cycling stability that were demonstrated in EDLC.
The Future of Cancer Diagnosis, Treatment and Surveillance: A Systemic Review on Immunotherapy and Immuno-PET Radiotracers
Authors: Liberini Virginia , Laudicella Riccardo , Capozza Martina , Huellner Martin W. , Burger Irene A. , Baldari Sergio , Terreno Enzo , Deandreis Désirée
Published: April 2021

Immunotherapy is an effective therapeutic option for several cancers. In the last years, the introduction of checkpoint inhibitors (ICIs) has shifted the therapeutic landscape in oncology and improved patient prognosis in a variety of neoplastic diseases. However, to date, the selection of the best patients eligible for these therapies, as well as the response assessment is still challenging. Patients are mainly stratified using an immunohistochemical analysis of the expression of antigens on biopsy specimens, such as PD-L1 and PD-1, on tumor cells, on peritumoral immune cells and/or in the tumor microenvironment (TME). Recently, the use and development of imaging biomarkers able to assess in-vivo cancer-related processes are becoming more important. Today, positron emission tomography (PET) with 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) is used routinely to evaluate tumor metabolism, and also to predict and monitor response to immunotherapy. Although highly sensitive, FDG-PET in general is rather unspecific. Novel radiopharmaceuticals (immuno-PET radiotracers), able to identify specific immune system targets, are under investigation in pre-clinical and clinical settings to better highlight all the mechanisms involved in immunotherapy. In this review, we will provide an overview of the main new immuno-PET radiotracers in development. We will also review the main players (immune cells, tumor cells and molecular targets) involved in immunotherapy. Furthermore, we report current applications and the evidence of using [18F]FDG PET in immunotherapy, including the use of artificial intelligence (AI).
BF3-OEt2 Catalyzed C3-Alkylation of Indole: Synthesis of Indolylsuccinimidesand Their Cytotoxicity Studies
Authors: Shaikh Iqbal N. , Rahim Abdul , Faazil Shaikh , Adil Syed Farooq , Assal Mohamed E. , Hatshan Mohammad Rafe
Published: April 2021

A simple and efficient BF3-OEt2 promoted C3-alkylation of indole has been developed to obtain3-indolylsuccinimidesfrom commercially available indoles and maleimides, with excellent yields under mild reaction conditions. Furthermore, anti-proliferative activity of these conjugates was evaluated against HT-29 (Colorectal), Hepg2 (Liver) and A549 (Lung) human cancer cell lines. One of the compounds, 3w, having N,N-Dimethylatedindolylsuccinimide is a potent congener amongst the series with IC50 value 0.02 µM and 0.8 µM against HT-29 and Hepg2 cell lines, respectively, and compound 3i was most active amongst the series with IC50 value 1.5 µM against A549 cells. Molecular docking study and mechanism of reaction have briefly beendiscussed. This method is better than previous reports in view of yield and substrate scope including electron deficient indoles.
Structural Batteries: A Review
Authors: Danzi Federico , Salgado Rui Martim , Oliveira Joana Espain , Arteiro Albertino , Camanho Pedro Ponces , Braga Maria Helena
Published: April 2021

Structural power composites stand out as a possible solution to the demands of the modern transportation system of more efficient and eco-friendly vehicles. Recent studies demonstrated the possibility to realize these components endowing high-performance composites with electrochemical properties. The aim of this paper is to present a systematic review of the recent developments on this more and more sensitive topic. Two main technologies will be covered here: (1) the integration of commercially available lithium-ion batteries in composite structures, and (2) the fabrication of carbon fiber-based multifunctional materials. The latter will be deeply analyzed, describing how the fibers and the polymeric matrices can be synergistically combined with ionic salts and cathodic materials to manufacture monolithic structural batteries. The main challenges faced by these emerging research fields are also addressed. Among them, the maximum allowable curing cycle for the embedded configuration and the realization that highly conductive structural electrolytes for the monolithic solution are noteworthy. This work also shows an overview of the multiphysics material models developed for these studies and provides a clue for a possible alternative configuration based on solid-state electrolytes.