bluuebunny/crossref_metadata_2025 huggingface dataset:
Community Pharmacists’ Opinions towards Poor Prescription Writing in Jazan, Saudi Arabia
Authors: Alqahtani Saad Saeed
Published: August 2021

Avoidance of medication errors is imperative for the safe use of medications, and community pharmacists are uniquely placed to identify and resolve the errors that may arise due to poorly handwritten prescriptions. Purpose: To explore the opinion and attitudes of community pharmacists towards poor prescription writing and their suggestions to overcome this concern. Methods: A cross-sectional, self-administered survey was conducted among the community pharmacists in the Jazan region, Saudi Arabia. Descriptive analysis and chi-square test were used at 5% p-value (p > 0.05) as the significance level. Results: The response rate for the survey was 78.66%, and 140 community pharmacists agreed to participate. Among the study subjects, the majority (73.57%) had a bachelor’s degree. Nearly three-fourths (3/4) of the pharmacists (72.29%) chose to send the patient back to the prescriber when they found difficulty in interpreting the information from an illegible prescription. As many as 80.71% of the pharmacists believed that poorly handwritten prescriptions were the cause of actual errors when dispensing medications. The most commonly encountered problem due to poorly handwritten prescriptions was the commercial name of medicine, which was reported by around two-thirds (67.86%) of the pharmacists. The use of e-prescription was suggested by 72.86% of the pharmacists as a probable solution to encounter this problem. Conclusion: Our findings highlight the belief and attitudes of community pharmacists in the region and their opinions to solve this impending problem of poor prescription writing. Continuous professional development courses can be adopted to tackle the problem. Additionally, health authorities can work on incorporating and facilitating the use of e-prescription in the community sector, which can be a boon to physicians, pharmacists, and patients. Proper and extensive training is however needed before the implementation of e-prescribing.
The Wooden Roof Framing Elements, Furniture and Furnishing of the Etruscan Domus of the Dolia of Vetulonia (Southern Tuscany, Italy)
Authors: Coradeschi Ginevra , Beltrame Massimo , Rafanelli Simona , Quaratesi Costanza , Sadori Laura , Barrocas Dias Cristina
Published: August 2021

The Etruscan Domus of the Dolia remained hidden until 2009, when archaeological excavations began in the Etruscan–Roman district of Vetulonia (Southern Tuscany). Based on the classification of the archaeological materials recovered, the destruction of the Domus and the Etruscan city of Vetulonia was traced back to the 1st century BC. The highly various and precious materials recovered inside the Domus revealed the richness of the building and its inhabitants. With this study, we present the anthracological analyses from the Domus of the Dolia. Wood charcoals were recovered from different house rooms, which had different functions based on the archaeological evidence. The tree species employed for the construction of the roof of the building were deciduous and semi-deciduous oak wood (Quercus sect. robur, Quercus sect. cerris) and silver fir wood (Abies cf. alba). Evergreen oak wood (Quercus sect. suber), boxwood (Buxus sempervirens), beech wood (Fagus cf. sylvatica), maple wood (Acer sp.) and cherry wood (Prunus cf. avium) were adopted for the furniture and furnishings of the house. Moreover, wood charcoal fragments of fruit trees belonging to the family of Rosaceae were identified, documenting a possible garden inside the court of the house. The study shows the use of the local tree species primarily. The silver fir wood and beech wood were likely sourced from the nearby (roughly 60 km) Mount Amiata.
Molecular Dynamics-Derived Pharmacophore Model Explaining the Nonselective Aspect of KV10.1 Pore Blockers
Authors: Toplak Žan , Merzel Franci , Pardo Luis A. , Peterlin Mašič Lucija , Tomašič Tihomir
Published: August 2021

The KV10.1 voltage-gated potassium channel is highly expressed in 70% of tumors, and thus represents a promising target for anticancer drug discovery. However, only a few ligands are known to inhibit KV10.1, and almost all also inhibit the very similar cardiac hERG channel, which can lead to undesirable side-effects. In the absence of the structure of the KV10.1–inhibitor complex, there remains the need for new strategies to identify selective KV10.1 inhibitors and to understand the binding modes of the known KV10.1 inhibitors. To investigate these binding modes in the central cavity of KV10.1, a unique approach was used that allows derivation and analysis of ligand–protein interactions from molecular dynamics trajectories through pharmacophore modeling. The final molecular dynamics-derived structure-based pharmacophore model for the simulated KV10.1–ligand complexes describes the necessary pharmacophore features for KV10.1 inhibition and is highly similar to the previously reported ligand-based hERG pharmacophore model used to explain the nonselectivity of KV10.1 pore blockers. Moreover, analysis of the molecular dynamics trajectories revealed disruption of the π–π network of aromatic residues F359, Y464, and F468 of KV10.1, which has been reported to be important for binding of various ligands for both KV10.1 and hERG channels. These data indicate that targeting the KV10.1 channel pore is also likely to result in undesired hERG inhibition, and other potential binding sites should be explored to develop true KV10.1-selective inhibitors as new anticancer agents.
Liquid Biopsy for Cancer Cachexia: Focus on Muscle-Derived microRNAs
Authors: Belli Roberta , Ferraro Elisabetta , Molfino Alessio , Carletti Raffaella , Tambaro Federica , Costelli Paola , Muscaritoli Maurizio
Published: August 2021

Cancer cachexia displays a complex nature in which systemic inflammation, impaired energy metabolism, loss of muscle and adipose tissues result in unintentional body weight loss. Cachectic patients have a poor prognosis and the presence of cachexia reduces the tolerability of chemo/radio-therapy treatments and it is frequently the primary cause of death in advanced cancer patients. Early detection of this condition could make treatments more effective. However, early diagnostic biomarkers of cachexia are currently lacking. In recent years, although solid biopsy still remains the “gold standard” for diagnosis of cancer, liquid biopsy is gaining increasing interest as a source of easily accessible potential biomarkers. Moreover, the growing interest in circulating microRNAs (miRNAs), has made these molecules attractive for the diagnosis of several diseases, including cancer. Some muscle-derived circulating miRNA might play a pivotal role in the onset/progression of cancer cachexia. This topic is of great interest since circulating miRNAs might be easily detectable by means of liquid biopsies and might allow an early diagnosis of this syndrome. We here summarize the current knowledge on circulating muscular miRNAs involved in muscle atrophy, since they might represent easily accessible and promising biomarkers of cachexia.
Local Therapies and Modulation of Tumor Surrounding Stroma in Malignant Pleural Mesothelioma: A Translational Approach
Authors: Lisini Daniela , Lettieri Sara , Nava Sara , Accordino Giulia , Frigerio Simona , Bortolotto Chandra , Lancia Andrea , Filippi Andrea Riccardo , Agustoni Francesco , Pandolfi Laura , Piloni Davide , Comoli Patrizia , Corsico Angelo Guido , Stella Giulia Maria
Published: August 2021

Malignant Pleural Mesothelioma (MPM) is a rare and aggressive neoplasm of the pleural mesothelium, mainly associated with asbestos exposure and still lacking effective therapies. Modern targeted biological strategies that have revolutionized the therapy of other solid tumors have not had success so far in the MPM. Combination immunotherapy might achieve better results over chemotherapy alone, but there is still a need for more effective therapeutic approaches. Based on the peculiar disease features of MPM, several strategies for local therapeutic delivery have been developed over the past years. The common rationale of these approaches is: (i) to reduce the risk of drug inactivation before reaching the target tumor cells; (ii) to increase the concentration of active drugs in the tumor micro-environment and their bioavailability; (iii) to reduce toxic effects on normal, non-transformed cells, because of much lower drug doses than those used for systemic chemotherapy. The complex interactions between drugs and the local immune-inflammatory micro-environment modulate the subsequent clinical response. In this perspective, the main interest is currently addressed to the development of local drug delivery platforms, both cell therapy and engineered nanotools. We here propose a review aimed at deep investigation of the biologic effects of the current local therapies for MPM, including cell therapies, and the mechanisms of interaction with the tumor micro-environment.
Decreased Interactions between Calmodulin and a Mutant Huntingtin Model Might Reduce the Cytotoxic Level of Intracellular Ca2+: A Molecular Dynamics Study
Authors: Moldovean Sanda Nastasia , Chiş Vasile
Published: August 2021

Mutant huntingtin (m-HTT) proteins and calmodulin (CaM) co-localize in the cerebral cortex with significant effects on the intracellular calcium levels by altering the specific calcium-mediated signals. Furthermore, the mutant huntingtin proteins show great affinity for CaM that can lead to a further stabilization of the mutant huntingtin aggregates. In this context, the present study focuses on describing the interactions between CaM and two huntingtin mutants from a biophysical point of view, by using classical Molecular Dynamics techniques. The huntingtin models consist of a wild-type structure, one mutant with 45 glutamine residues and the second mutant with nine additional key-point mutations from glutamine residues into proline residues (9P(EM) model). Our docking scores and binding free energy calculations show higher binding affinities of all HTT models for the C-lobe end of the CaM protein. In terms of dynamic evolution, the 9P(EM) model triggered great structural changes into the CaM protein’s structure and shows the highest fluctuation rates due to its structural transitions at the helical level from α-helices to turns and random coils. Moreover, our proposed 9P(EM) model suggests much lower interaction energies when compared to the 45Qs-HTT mutant model, this finding being in good agreement with the 9P(EM)’s antagonistic effect hypothesis on highly toxic protein–protein interactions.
The Role of Biomarkers in Atherothrombotic Stroke—A Systematic Review
Authors: Andone Sebastian , Bajko Zoltan , Motataianu Anca , Mosora Oana , Balasa Rodica
Published: August 2021

Stroke represents the primary debilitating disease in adults and is the second-highest cause of death worldwide. Atherosclerosis, the most prevalent etiology for vascular conditions, is a continuous process that gradually creates and develops endothelial lesions known as atherosclerotic plaques. These lesions lead to the appearance of atherothrombotic stroke. In the last decades, the role of biological biomarkers has emerged as either diagnostic, prognostic, or therapeutic targets. This article aims to create a list of potential biomarkers related to atherothrombotic stroke by reviewing the currently available literature. We identified 23 biomarkers and assessed their roles as risk factors, detection markers, prognostic predictors, and therapeutic targets. The central aspect of these biomarkers is related to risk stratification, especially for patients who have not yet suffered a stroke. Other valuable data are focused on the predictive capabilities for stroke patients regarding short-term and long-term prognosis, including their influence over the acute phase treatment, such as rt-PA thrombolysis. Although the role of biomarkers is anticipated to be of extreme value in the future, they cannot yet compete with traditional stroke neuroimaging markers but could be used as additional tools for etiological diagnosis.
Genetics and Inflammation in Endometriosis: Improving Knowledge for Development of New Pharmacological Strategies
Authors: Giacomini Elisa , Minetto Sabrina , Li Piani Letizia , Pagliardini Luca , Somigliana Edgardo , Viganò Paola
Published: August 2021

According to a rich body of literature, immune cell dysfunctions, both locally and systemically, and an inflammatory environment characterize all forms of endometriosis. Alterations in transcripts and proteins involved in the recruitment of immune cells, in the interaction between cytokines and their receptors, cellular adhesion and apoptosis have been demonstrated in endometriotic lesions. The objective of this narrative review is to provide an overview of the components and mechanisms at the intersection between inflammation and genetics that may constitute vanguard therapeutic approaches in endometriosis. The GWAS technology and pathway-based analysis highlighted the role of the MAPK and the WNT/β-catenin cascades in the pathogenesis of endometriosis. These signaling pathways have been suggested to interfere with the disease establishment via several mechanisms, including apoptosis, migration and angiogenesis. Extracellular vesicle-associated molecules may be not only interesting to explain some aspects of endometriosis progression, but they may also serve as therapeutic regimens per se. Immune/inflammatory dysfunctions have always represented attractive therapeutic targets in endometriosis. These would be even more interesting if genetic evidence supported the involvement of functional pathways at the basis of these alterations. Targeting these dysfunctions through next-generation inhibitors can constitute a therapeutic alternative for endometriosis.
Molecular Regulatory Networks for Improving Nitrogen Use Efficiency in Rice
Authors: Hou Mengmeng , Yu Ming , Li Zhiqiang , Ai Zhiyuan , Chen Jingguang
Published: August 2021

Nitrogen is an important factor limiting the growth and yield of rice. However, the excessive application of nitrogen will lead to water eutrophication and economic costs. To create rice varieties with high nitrogen use efficiency (NUE) has always been an arduous task in rice breeding. The processes for improving NUE include nitrogen uptake, nitrogen transport from root to shoot, nitrogen assimilation, and nitrogen redistribution, with each step being indispensable to the improvement of NUE. Here, we summarize the effects of absorption, transport, and metabolism of nitrate, ammonium, and amino acids on NUE, as well as the role of hormones in improving rice NUE. Our discussion provide insight for further research in the future.
Cell-Free Hemoglobin Does Not Attenuate the Effects of SARS-CoV-2 Spike Protein S1 Subunit in Pulmonary Endothelial Cells
Authors: Jana Sirsendu , Heaven Michael R. , Alayash Abdu I.
Published: August 2021

SARS-CoV-2 primarily infects epithelial airway cells that express the host entry receptor angiotensin-converting enzyme 2 (ACE2), which binds to the S1 spike protein on the surface of the virus. To delineate the impact of S1 spike protein interaction with the ACE2 receptor, we incubated the S1 spike protein with human pulmonary arterial endothelial cells (HPAEC). HPAEC treatment with the S1 spike protein caused disruption of endothelial barrier function, increased levels of numerous inflammatory molecules (VCAM-1, ICAM-1, IL-1β, CCL5, CXCL10), elevated mitochondrial reactive oxygen species (ROS), and a mild rise in glycolytic reserve capacity. Because low oxygen tension (hypoxia) is associated with severe cases of COVID-19, we also evaluated treatment with hemoglobin (HbA) as a potential countermeasure in hypoxic and normal oxygen environments in analyses with the S1 spike protein. We found hypoxia downregulated the expression of the ACE2 receptor and increased the critical oxygen homeostatic signaling protein, hypoxia-inducible factor (HIF-1α); however, treatment of the cells with HbA yielded no apparent change in the levels of ACE2 or HIF-1α. Use of quantitative proteomics revealed that S1 spike protein-treated cells have few differentially regulated proteins in hypoxic conditions, consistent with the finding that ACE2 serves as the host viral receptor and is reduced in hypoxia. However, in normoxic conditions, we found perturbed abundance of proteins in signaling pathways related to lysosomes, extracellular matrix receptor interaction, focal adhesion, and pyrimidine metabolism. We conclude that the spike protein alone without the rest of the viral components is sufficient to elicit cell signaling in HPAEC, and that treatment with HbA failed to reverse the vast majority of these spike protein-induced changes.
Natural Killer Cells and Type 1 Innate Lymphoid Cells in Hepatocellular Carcinoma: Current Knowledge and Future Perspectives
Authors: Jacquelot Nicolas , Seillet Cyril , Souza-Fonseca-Guimaraes Fernando , Sacher Adrian G. , Belz Gabrielle T. , Ohashi Pamela S.
Published: August 2021

Natural killer (NK) cells and type 1 innate lymphoid cells (ILC1) are specific innate lymphoid cell subsets that are key for the detection and elimination of pathogens and cancer cells. In liver, while they share a number of characteristics, they differ in many features. These include their developmental pathways, tissue distribution, phenotype and functions. NK cells and ILC1 contribute to organ homeostasis through the production of key cytokines and chemokines and the elimination of potential harmful bacteria and viruses. In addition, they are equipped with a wide range of receptors, allowing them to detect “stressed cells’ such as cancer cells. Our understanding of the role of innate lymphoid cells in hepatocellular carcinoma (HCC) is growing owing to the development of mouse models, the progress in immunotherapeutic treatment and the recent use of scRNA sequencing analyses. In this review, we summarize the current understanding of NK cells and ILC1 in hepatocellular carcinoma and discuss future strategies to take advantage of these innate immune cells in anti-tumor immunity. Immunotherapies hold great promise in HCC, and a better understanding of the role and function of NK cells and ILC1 in liver cancer could pave the way for new NK cell and/or ILC1-targeted treatment.
Immunomodulatory Arming Factors—The Current Paradigm for Oncolytic Vectors Relies on Immune Stimulating Molecules
Authors: Peters Cole W. D. , Nigim Fares
Published: August 2021

The dogma of engineering oncolytic viral vectors has shifted from emphasizing the viral lysis of individual cancer cells to the recruitment and coordination of the adaptive immune system to clear the tumor. To accomplish this, researchers have been adding several classes of transgenes to their preferred viral platforms. The most prevalent of these include antibodies and targeting moieties, interleukins and cytokines, and genes which rely on small molecule co-administration for tumor killing. Most current vectors rely exclusively on one of these types of transgenes to elicit the desired immune response to clear tumors, but are not mutually exclusive, with several larger OVs armed with several of these factors. The common theme of emerging armed vectors is to simply initiate or enhance infiltration of effector CD8+ T cells to clear the tumor locally at OV infection sites, and systemically throughout the body where the OV has not infected tumor cells. The precision of oncolytic vectors to target a cell type or tissue remains its key advantage over small-molecule drugs. Unlike chemo- and other drug therapies, viral vectors can be made to specifically infect and grow within tumor cells. This ensures localized expression of the therapeutic transgene to the diseased tissue, thereby limiting systemic toxicity. This review will examine the immunomodulating transgenes of current OVs, describe their general effect on the immune system, and provide the rationale for each vector’s use in clearing its targeted tumor.
The Role of Exosome and the ESCRT Pathway on Enveloped Virus Infection
Authors: Ju Yichen , Bai Haocheng , Ren Linzhu , Zhang Liying
Published: August 2021

The endosomal sorting complex required for transport (ESCRT) system consists of peripheral membrane protein complexes ESCRT-0, -I, -II, -III VPS4-VTA1, and ALIX homodimer. This system plays an important role in the degradation of non-essential or dangerous plasma membrane proteins, the biogenesis of lysosomes and yeast vacuoles, the budding of most enveloped viruses, and promoting membrane shedding of cytokinesis. Recent results show that exosomes and the ESCRT pathway play important roles in virus infection. This review mainly focuses on the roles of exosomes and the ESCRT pathway in virus assembly, budding, and infection of enveloped viruses. The elaboration of the mechanism of exosomes and the ESCRT pathway in some enveloped viruses provides important implications for the further study of the infection mechanism of other enveloped viruses.
Suppression of LPS-Induced Inflammation and Cell Migration by Azelastine through Inhibition of JNK/NF-κB Pathway in BV2 Microglial Cells
Authors: Nguyen Phuong Linh , Bui Bich Phuong , Duong Men Thi Hoai , Lee Kyeong , Ahn Hee-Chul , Cho Jungsook
Published: August 2021

The c-Jun N-terminal kinases (JNKs) are implicated in many neuropathological conditions, including neurodegenerative diseases. To explore potential JNK3 inhibitors from the U.S. Food and Drug Administration-approved drug library, we performed structure-based virtual screening and identified azelastine (Aze) as one of the candidates. NMR spectroscopy indicated its direct binding to the ATP-binding site of JNK3, validating our observations. Although the antihistamine effect of Aze is well documented, the involvement of the JNK pathway in its action remains to be elucidated. This study investigated the effects of Aze on lipopolysaccharide (LPS)-induced JNK phosphorylation, pro-inflammatory mediators, and cell migration in BV2 microglial cells. Aze was found to inhibit the LPS-induced phosphorylation of JNK and c-Jun. It also inhibited the LPS-induced production of pro-inflammatory mediators, including interleukin-6, tumor necrosis factor-α, and nitric oxide. Wound healing and transwell migration assays indicated that Aze attenuated LPS-induced BV2 cell migration. Furthermore, Aze inhibited LPS-induced IκB phosphorylation, thereby suppressing nuclear translocation of NF-κB. Collectively, our data demonstrate that Aze exerts anti-inflammatory and anti-migratory effects through inhibition of the JNK/NF-κB pathway in BV2 cells. Based on our findings, Aze may be a potential candidate for drug repurposing to mitigate neuroinflammation in various neurodegenerative disorders, including Alzheimer’s and Parkinson’s diseases.
Paradoxical Pro-angiogenic Effect of Low-Dose Ellipticine Identified by In Silico Drug Repurposing
Authors: Oh Jisu , Lee Hyeon Hae , Jeong Yunhui , Yoon Siyeong , An Hyun-Ju , Baek Minjung , Kim Do Kyung , Lee Soonchul
Published: August 2021

Inadequate vessel maintenance or growth causes ischemia in diseases such as myocardial infarction, stroke, and neurodegenerative disorders. Therefore, developing an effective strategy to salvage ischemic tissues using a novel compound is urgent. Drug repurposing has become a widely used method that can make drug discovery more efficient and less expensive. Additionally, computational virtual screening tools make drug discovery faster and more accurate. This study found a novel drug candidate for pro-angiogenesis by in silico virtual screening. Using Gene Expression Omnibus (GEO) microarray datasets related to angiogenesis studies, differentially expressed genes were identified and characteristic direction signatures extracted from GEO2EnrichR were used as input data on L1000CDS2 to screen pro-angiogenic molecules. After a thorough review of the candidates, a list of compounds structurally similar to TWS-119 was generated using ChemMine Tools and its clustering toolbox. ChemMine Tools and ChemminR structural similarity search tools for small-molecule analysis and clustering were used for second screening. A molecular docking simulation was conducted using AutoDock v.4 to evaluate the physicochemical effect of secondary-screened chemicals. A cell viability or toxicity test was performed to determine the proper dose of the final candidate, ellipticine. As a result, we found ellipticine, which has pro-angiogenic effects, using virtual computational methods. The noncytotoxic concentration of ellipticine was 156.25 nM. The phosphorylation of glycogen synthase kinase-3β was decreased, whereas the β-catenin expression was increased in human endothelial cells treated with ellipticine. We concluded that ellipticine at sublethal dosage could be successfully repositioned as a pro-angiogenic substance by in silico virtual screening.
Molecular Mechanisms of Skewed X-Chromosome Inactivation in Female Hemophilia Patients—Lessons from Wide Genome Analyses
Authors: Dardik Rima , Avishai Einat , Lalezari Shadan , Barg Assaf A. , Levy-Mendelovich Sarina , Budnik Ivan , Barel Ortal , Khavkin Yulia , Kenet Gili , Livnat Tami
Published: August 2021

Introduction: Hemophilia A (HA) is an X-linked bleeding disorder caused by factor VIII (FVIII) deficiency or dysfunction due to F8 gene mutations. HA carriers are usually asymptomatic because their FVIII levels correspond to approximately half of the concentration found in healthy individuals. However, in rare cases, a carrier may exhibit symptoms of moderate to severe HA primarily due to skewed inactivation of her non-hemophilic X chromosome. Aim: The aim of the study was to investigate X-chromosome inactivation (XCI) patterns in HA carriers, with special emphasis on three karyotypically normal HA carriers presenting with moderate to severe HA phenotype due to skewed XCI, in an attempt to elucidate the molecular mechanism underlying skewed XCI in these symptomatic HA carriers. The study was based on the hypothesis that the presence of a pathogenic mutation on the non-hemophilic X chromosome is the cause of extreme inactivation of that X chromosome. Methods: XCI patterns were studied by PCR analysis of the CAG repeat region in the HUMARA gene. HA carriers that demonstrated skewed XCI were further studied by whole-exome sequencing (WES) followed by X chromosome-targeted bioinformatic analysis. Results: All three HA carriers presenting with the moderate to severe HA phenotype due to skewed XCI were found to carry pathogenic mutations on their non-hemophilic X chromosomes. Patient 1 was diagnosed with a frameshift mutation in the PGK1 gene that was associated with familial XCI skewing in three generations. Patient 2 was diagnosed with a missense mutation in the SYTL4 gene that was associated with familial XCI skewing in two generations. Patient 3 was diagnosed with a nonsense mutation in the NKAP gene that was associated with familial XCI skewing in two generations. Conclusion: Our results indicate that the main reason for skewed XCI in our female HA patients was negative selection against cells with a disadvantage caused by an additional deleterious mutation on the silenced X chromosome, thus complicating the phenotype of a monogenic X-linked disease. Based on our study, we are currently offering the X inactivation test to symptomatic hemophilia carriers and plan to expand this approach to symptomatic carriers of other X-linked diseases, which can be further used in pregnancy planning.
A Brief Review on the High-Energy Electromagnetic Radiation-Shielding Materials Based on Polymer Nanocomposites
Authors: Acevedo-Del-Castillo Angel , Águila-Toledo Ernesto , Maldonado-Magnere Santiago , Aguilar-Bolados Héctor
Published: August 2021

This paper revises the use of polymer nanocomposites to attenuate high-energy electromagnetic radiation (HE-EMR), such as gamma radiation. As known, high-energy radiation produces drastic damage not only in facilities or electronic devices but also to life and the environment. Among the different approaches to attenuate the HE-EMR, we consider the use of compounds with a high atomic number (Z), such as lead, but as known, lead is toxic. Therefore, different works have considered low-toxicity post-transitional metal-based compounds, such as bismuth. Additionally, nanosized particles have shown higher performance to attenuate HE-EMR than those that are micro-sized. On the other hand, materials with π-conjugated systems can also play a role in spreading the energy of electrons ejected as a consequence of the interaction of HE-EMR with matter, preventing the ionization and bond scission of polymers. The different effects produced by the interactions of the matter with HE-EMR are revised. The increase of the shielding properties of lightweight, flexible, and versatile materials such as polymer-based materials can be a contribution for developing technologies to obtain more efficient materials for preventing the damage produced for the HE-EMR in different industries where it is found.
Nanomedicine for Neurodegenerative Disorders: Focus on Alzheimer’s and Parkinson’s Diseases
Authors: Jagaran Keelan , Singh Moganavelli
Published: August 2021

Neurodegenerative disorders involve the slow and gradual degeneration of axons and neurons in the central nervous system (CNS), resulting in abnormalities in cellular function and eventual cellular demise. Patients with these disorders succumb to the high medical costs and the disruption of their normal lives. Current therapeutics employed for treating these diseases are deemed palliative. Hence, a treatment strategy that targets the disease’s cause, not just the symptoms exhibited, is desired. The synergistic use of nanomedicine and gene therapy to effectively target the causative mutated gene/s in the CNS disease progression could provide the much-needed impetus in this battle against these diseases. This review focuses on Parkinson’s and Alzheimer’s diseases, the gene/s and proteins responsible for the damage and death of neurons, and the importance of nanomedicine as a potential treatment strategy. Multiple genes were identified in this regard, each presenting with various mutations. Hence, genome-wide sequencing is essential for specific treatment in patients. While a cure is yet to be achieved, genomic studies form the basis for creating a highly efficacious nanotherapeutic that can eradicate these dreaded diseases. Thus, nanomedicine can lead the way in helping millions of people worldwide to eventually lead a better life.
Programmed Cell Death in Developing Brachypodium distachyon Grain
Authors: Saada Safia , Solomon Charles Ugochukwu , Drea Sinéad
Published: August 2021

The normal developmental sequence in a grass grain entails the death of several maternal and filial tissues in a genetically regulated process termed programmed cell death (PCD). The progression and molecular aspects of PCD in developing grains have been reported for domesticated species such as barley, rice, maize and wheat. Here, we report a detailed investigation of PCD in the developing grain of the wild model species Brachypodium distachyon. We detected PCD in developing Brachypodium grains using molecular and histological approaches. We also identified in Brachypodium the orthologs of protease genes known to contribute to grain PCD and surveyed their expression. We found that, similar to cereals, PCD in the Brachypodium nucellus occurs in a centrifugal pattern following anthesis. However, compared to cereals, the rate of post-mortem clearance in the Brachypodium nucellus is slower. However, compared to wheat and barley, mesocarp PCD in Brachypodium proceeds more rapidly in lateral cells. Remarkably, Brachypodium mesocarp PCD is not coordinated with endosperm development. Phylogenetic analysis suggests that barley and wheat possess more vacuolar processing enzymes that drive nucellar PCD compared to Brachypodium and rice. Our expression analysis highlighted putative grain-specific PCD proteases in Brachypodium. Combined with existing knowledge on grain PCD, our study suggests that the rate of nucellar PCD moderates grain size and that the pattern of mesocarp PCD influences grain shape.
Otoplasty through Ventral Skin Incision and Shaping of the Antihelix by Abrasion—A Retrospective Study
Authors: Kühn Shafreena , Wöhler Nadine , Wehle Andrej , Küenzlen Lara , Rothenberger Jens , Sader Robert , Lemperle Gottfried , Rieger Ulrich Michael
Published: August 2021

(1) Background: Protruding ears are the most common auricular malformation affecting approximately 5% of the population. One common factor leading to auricular protrusion is a deficiency or total absence of the antihelix. A technique first described by Gottfried Lemperle in 2003 attempts cartilage thinning, folding, and fixation by non-absorbable mattress sutures after ventral skin incision along the ventral helical rim. (2) Methods: Retrospective analysis of patient records was performed for otoplasties according to this technique, performed between 1985 and 2014 at Agaplesion Markus Hospital in Frankfurt, Germany. All recorded complications were examined. (3) Results: A total of 912 single otoplasties were performed according to this technique from 1985 to 2014. Overall complications included 26% minor complications not requiring further surgery and 11% major complications leading to revision surgery. Within those requiring revision surgery, the most common reason was recurrence of auricular protrusion (5%), followed by suture granulomas (5%) and hematomas (2%). (4) Conclusions: Lemperle’s otoplasty technique addresses the open thinning and shaping of the antihelix through a ventral incision along the helix to prevent irregularities and possible ridges. Results show a low complication rate comparable to data found in published studies. This technique is easy to perform, safe, and avoids often seen contour irregularities of the antihelix compared to techniques with a posterior approach.
The Versatility of HVOF Burner Rig Testing for Ceramic Matrix Composite Evaluation
Authors: Morscher Gregory N. , Panakarajupally Ragav P. , Hoffman Leland
Published: August 2021

Effective testing of ceramic matrix composites (CMCs) and CMC/coating systems for high temperature, high stress, high velocity and/or severe oxidation/corrosion environments is a critical need in materials/coatings evaluation for extreme environments of hot section parts in jet engine and hypersonic applications. Most current technology can evaluate two or three of the extreme conditions for a given application; however, incorporating as many of the extreme thermo-mechanical-environmental factors is highly advantageous to understand combinatorial effects. A high velocity oxygen fuel (HVOF) burner rig offers an excellent platform to evaluate many of these extreme conditions. In this work, the following three different thermo-mechanical-environmental test conditions using an HVOF rig on SiC-based CMCs are highlighted: (1) fatigue at temperature for >Mach 1 velocity and high temperature compared to typical stagnant air test environment, (2) high temperature hard particle erosion at temperature for ≤Mach 1 conditions and (3) ~Mach 5 near-hypersonic velocity conditions at very high temperature exposure.
A Comparative Study on Fatigue Response of Aluminum Alloy Friction Stir Welded Joints at Various Post-Processing and Treatments
Authors: Hassanifard Soran , Varvani-Farahani Ahmad
Published: August 2021

The present study examines the fatigue of friction stir welded (FSW) aluminum 6061, 7075, 1060 joints followed by (i) in situ and sequential rolling (SR) processes, (ii) plastic burnishing (iii) solution-treatment artificial aging (STA), (iv) local alloying through depositing thin copper foils, and (v) inserting alumina powder in the weld nugget zone (NZ). The microstructural features and fatigue life of post-processed joints were compared with those of as-welded joints. The in situ rolling technique offered simultaneous rolling and welding operations of aluminum joints, while through the sequential rolling process, the top surface of FSW joints was rolled after the welding process. The fatigue life of in situ rolled samples was increased as the ball diameter of welding tool increased. The fatigue life of friction stir welded joints after a low-plasticity burnishing process was noticeably promoted. The addition of 1 wt.% alumina in the NZ of joints resulted in a significant elevation on fatigue life of friction stir spot welded joints, while an increase in alumina powder to 2.5 wt.% adversely affected fatigue strength. Weld NZ was alloyed through the insertion of copper foils between the faying surfaces of joints. This localized alloy slightly improved the fatigue life of joints; however, its effects on fatigue life were not as influential as STA heat-treated or in situ rolled joints. The microstructure of weld joints was highly affected through post-processing and treatments, resulting in a substantial influence on the fatigue response of FSW aluminum joints.
A Universal Simulation Framework of Shipborne Inertial Sensors Based on the Ship Motion Model and Robot Operating System
Authors: Jing Qianfeng , Wang Haichao , Hu Bin , Liu Xiuwen , Yin Yong
Published: August 2021

A complete virtual test environment is a powerful tool for Autonomous Surface Vessels (ASVs) research, and the simulation of ship motion and shipborne sensors is one of the prerequisites for constructing such an environment. This paper proposed a universal simulation framework of shipborne inertial sensors. A ship motion model considering environmental disturbances is proposed to simulate the six-degrees-of-freedom motion of ships. The discrete form of the inertial sensor stochastic error model is derived. The inertial measurement data are simulated by adding artificial errors to a simulated motion status. In addition, the ship motion simulation, inertial measurement simulation, and environment simulation nodes are implemented based on the computational graph architecture of the Robot Operating System (ROS). The benefit from the versatility of the ROS messages, the format of simulated inertial measurement is exactly the same as that of real sensors, which provides a research basis for the fusion perception algorithm based on visual–inertial and laser–inertial sensors in the research field of ASVs.
The Endophytic Fungus Piriformospora Indica-Assisted Alleviation of Cadmium in Tobacco
Authors: Su Zhenzhu , Zeng Yulan , Li Xiaoli , Perumal Anand Babu , Zhu Jianan , Lu Xuanjun , Dai Mengdi , Liu Xiaohong , Lin Fucheng
Published: August 2021

Increasing evidence suggests that the endophytic fungus Piriformospora indica helps plants overcome various abiotic stresses, especially heavy metals. However, the mechanism of heavy metal tolerance has not yet been elucidated. Here, the role of P. indica in alleviating cadmium (Cd) toxicities in tobacco was investigated. It was found that P. indica improved Cd tolerance to tobacco, increasing Cd accumulation in roots but decreasing Cd accumulation in leaves. The colonization of P. indica altered the subcellular repartition of Cd, increasing the Cd proportion in cell walls while reducing the Cd proportion in membrane/organelle and soluble fractions. During Cd stress, P. indica significantly enhanced the peroxidase (POD) activity and glutathione (GSH) content in tobacco. The spatial distribution of GSH was further visualized by Raman spectroscopy, showing that GSH was distributed in the cortex of P. indica-inoculated roots while in the epidermis of the control roots. A LC-MS/MS-based label-free quantitative technique evaluated the differential proteomics of P. indica treatment vs. control plants under Cd stress. The expressions of peroxidase, glutathione synthase, and photosynthesis-related proteins were significantly upregulated. This study provided extensive evidence for how P. indica enhances Cd tolerance in tobacco at physiological, cytological, and protein levels.
Techno-Stress: Damage Caused by New Emerging Risks
Authors: Elizalde Rubén Rodríguez
Published: August 2021

The world moves and advances very quickly. Production systems and jobs evolve with the world. Occupational risks change as jobs change: The occupational risks of jobs we found two hundred years ago are different from the risks inherent to today’s jobs. The influence of technology is evident in many of today’s companies and, as a consequence, in the work that takes place in them. The recent COVID-19 pandemic, which has so upset the world, has made possible the acceleration in the massive use of certain communication tools that has been linked to the home confinement of a significant part of the population. Lots of workers and companies have been forced to telecommute. In a lot of countries, legislation and regulations were not prepared for these new ways of working: the laws have had to adapt to this new operation. In this area techno-stress has emerged, a new variety of stress derived from the use of new technologies at work, with the consequent negative psychosocial effects for the worker and the people around him, which can, at the same time, be the prelude to many others pathological processes of various nature.
Shape Analysis of the Elastic Deformation Region throughout the Axi-Symmetric Wire Drawing Process of ETP Grade Copper
Authors: Strzępek Paweł , Mamala Andrzej , Zasadzińska Małgorzata , Kiesiewicz Grzegorz , Knych Tadeusz Antoni
Published: August 2021

The wire drawing process is commonly perceived as one of the best studied metal forming processes in almost every aspect; however, when considering elastic deformation, researchers usually focus on the uniaxial tensile forces after the material exits the drawing die and not the elastic deformation region before entering the drawing die, even though it may have a significant impact on the strength parameters and the nature of metal flow inside the drawing die. The aim of this research is to theoretically and experimentally identify the deformation in the elastic region and to further link the shape of this region and the values of stress occurring in it with the geometrical parameters of the drawing process and assess its impact on its strength parameters. In order to achieve the assumed goals, numerical analyses using the finite element method and experimental research on the drawing process in laboratory conditions were carried out using Vickers hardness tests and resistance strain gauges measuring deformation in stationary and non-stationary conditions. The obtained results indicate that the shape and the extent of the region of elastic deformations generated in the material before the plastic deformation region during the drawing process depends on the applied deformation coefficient and stationarity of the process.
Interfacial Friction Anisotropy in Few-Layer Van der Waals Crystals
Authors: Wang Kaibo , Li Hao , Guo Yufeng
Published: August 2021

Friction anisotropy is one of the important friction behaviors for two-dimensional (2D) van der Waals (vdW) crystals. The effects of normal pressure and thickness on the interfacial friction anisotropy in few-layer graphene, h-BN, and MoSe2 under constant normal force mode have been extensively investigated by first-principle calculations. The increase of normal pressure and layer number enhances the interfacial friction anisotropy for graphene and h-BN but weakens that for MoSe2. Such significant deviations in the interfacial friction anisotropy of few-layer graphene, h-BN and MoSe2 can be mainly attributed to the opposite contributions of electron kinetic energies and electrostatic energies to the sliding energy barriers and different interlayer charge exchanges. Our results deepen the understanding of the influence of external loading and thickness on the friction properties of 2D vdW crystals.
Biofabrication of a Low Modulus Bioelectroprobe for Neurons to Grow Into
Authors: Hao Zhiyan , Wang Sen , Zhang Kun , Zhou Jiajia , Li Dichen , He Jiankang , Gao Lin , Wang Ling
Published: August 2021

Implantable nerve electrodes, as a bridge between the brain and external devices, have been widely used in areas such as brain function exploration, neurological disease treatment and human–computer interaction. However, the mechanical properties mismatch between the electrode material and the brain tissue seriously affects the stability of electrode signal acquisition and the effectiveness of long-term service in vivo. In this study, a modified neuroelectrode was developed with conductive biomaterials. The electrode has good biocompatibility and a gradient microstructure suitable for cell growth. Compared with metal electrodes, bioelectrodes not only greatly reduced the elastic modulus (<10 kpa) but also increased the conductivity of the electrode by 200 times. Through acute electrophysiological analysis and a 12-week chronic in vivo experiment, the bioelectrode clearly recorded the rat’s brain electrical signals, effectively avoided the generation of glial scars and induced neurons to move closer to the electrode. The new conductive biomaterial electrodes developed in this research make long-term implantation of cortical nerve electrodes possible.
A Literature Review of Concrete Ability to Sustain Strength after Fire Exposure Based on the Heat Accumulation Factor
Authors: Pasztetnik Michał , Wróblewski Roman
Published: August 2021

Concrete is susceptible to damage during and after high-temperature exposure (most frequently in fire). The concrete partial strength re-gain after a high-temperature exposure obtained by the rehydration process is undoubtedly an advantage of this construction material. However, to use fire-damaged concrete, one has to know why the strength deteriorates and what makes the partial re-gain. Within this framework, the paper aims to find what factors influence the strength re-gain. Moreover, an attempt is made to introduce a measure collecting various influences such as the modified heat accumulation factor—accounting only for that which is important for the process, the temperature decomposing cement paste (i.e., above 400 °C). Several factors, i.e., peak temperature, heating time and rate, cooling regime, post-fire re-curing, concrete composition, age of concrete at exposure, porosity, load level at exposure, and heat accumulation are presented by their influence on the relative residual compressive strength, i.e., a portion of initial strength that is obtained after temperature exposure and strength re-gain. Since the relative strength unifies various concretes, a more general assessment and discussion are presented based on the experimental results and correlation factors. As fundamental influences determining the residual strength, the heating time, peak temperature, cooling, or post-heating re-curing regimes are found with the load level at exposure being inadequately examined. This paper also shows the superiority of the modified heat accumulation factor, but the results obtained are not satisfactory, and additional experimental data are necessary to develop a theoretical model of the residual strength.