bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of Persistent Uncontrolled Asthma Symptoms in Community Members Exposed to World Trade Center Dust and Fumes
Authors: Reibman Joan , Caplan-Shaw Caralee , Wu Yinxiang , Liu Mengling , Amin Milan R. , Berger Kenneth I. , Cotrina-Vidal Maria L. , Kazeros Angeliki , Durmus Nedim , Fernandez-Beros Maria-Elena , Goldring Roberta M. , Rosen Rebecca , Shao Yongzhao
Published: September 2020

The destruction of the World Trade Center (WTC) towers on the 11th of September, 2001 released a vast amount of aerosolized dust and smoke resulting in acute and chronic exposures to community members as well as responders. The WTC Environmental Health Center (WTC EHC) is a surveillance and treatment program for a diverse population of community members, including local residents and local workers with WTC dust exposure. Many of these patients have reported persistent lower respiratory symptoms (LRS) despite treatment for presumed asthma. Our goal was to identify conditions associated with persistent uncontrolled LRS despite standard asthma management. We recruited 60 patients who were uncontrolled at enrollment and, after a three-month run-in period on high-dose inhaled corticosteroid and long acting bronchodilator, reassessed their status as Uncontrolled or Controlled based on a score from the Asthma Control Test (ACT). Despite this treatment, only 11 participants (18%) gained Controlled status as defined by the ACT. We compared conditions associated with Uncontrolled and Controlled status. Those with Uncontrolled symptoms had higher rates of upper airway symptoms. Many patients had persistent bronchial hyper-reactivity (BHR) and upper airway hyper-reactivity as measured by paradoxical vocal fold movement (PVFM). We found a significant increasing trend in the percentage of Controlled with respect to the presence of BHR and PVFM. We were unable to identify significant differences in lung function or inflammatory markers in this small group. Our findings suggest persistent upper and lower airway hyper-reactivity that may respond to standard asthma treatment, whereas others with persistent LRS necessitate additional diagnostic evaluation, including a focus on the upper airway.
Passing Networks and Tactical Action in Football: A Systematic Review
Authors: Caicedo-Parada Sergio , Lago-Peñas Carlos , Ortega-Toro Enrique
Published: September 2020

The aim of this study is to examine the most significant literature on network analyses and factors associated with tactical action in football. A systematic review was conducted on Web of Science, taking into account the PRISMA guidelines using the keyword “network”, associated with “football” or “soccer”. The search yielded 162 articles, 24 of which met the inclusion criteria. Significant results: (a) 50% of the studies ratify the importance of network structures, quantifying and comparing properties to determine the applicability of the results instead of analyzing them separately; (b) 12.5% analyze the process of offensive sequences and communication between teammates by means of goals scored; (c) the studies mainly identify a balance in the processes of passing networks; (d) the variables allowed for the interpretation of analyses of grouping metrics, centralization, density and heterogeneity in connections between players of the same team. Finally, a systematic analysis provides a functional understanding of knowledge that will help improve the performance of players and choose the most appropriate response within the circumstances of the game.
Process, Practice and Progress: A Case Study of the Health Impact Assessment (HIA) of Brexit in Wales
Authors: Green Liz , Ashton Kathryn , Edmonds Nerys , Azam Sumina
Published: September 2020

Health impact assessment (HIA) is a systematic and flexible tool, which is advocated by the World Health Organisation as a method through which to consider the impact of policies on the health and well-being of a population, and the inequalities that may arise because of it. In 2018, the HIA support unit in Wales carried out a comprehensive and unique HIA on the impact of Brexit in Wales. The aims were to understand the differential impacts that Brexit would have on the health and well-being of the population and to provide evidence to inform decision makers across a range of public bodies. It followed a five-step process for HIA and utilised a wide range of evidence sources and health intelligence including both quantitative and qualitative evidence. This paper reflects on the process of carrying out the HIA and the methods used. It discusses the stages of the HIA, and shares the findings and reflections of implementation which will be beneficial to other HIA practitioners and policy makers. It does not concentrate on the findings of the HIA in detail, but focusses on what worked and any challenges encountered. It has been used to progress the practice of HIA in Wales and demonstrates the value of HIA as a method to inform and influence complex decisions.
A Review of Psychological Issues among Patients and Healthcare Staff during Two Major Coronavirus Disease Outbreaks in China: Contributory Factors and Management Strategies
Authors: Chow Ka Ming , Law Bernard M.H. , Ng Marques S.N. , Chan Dorothy N.S. , So Winnie K.W. , Wong Cho Lee , Chan Carmen W.H.
Published: September 2020

Outbreaks of severe acute respiratory syndrome (SARS) and coronavirus disease 2019 (COVID-19) have affected populations worldwide. Our literature review summarises the studies reporting psychological issues among healthcare staff and infected patients in mainland China, Hong Kong, and Taiwan during these two outbreaks and the potential strategies for addressing these issues. Our review shows that patients and healthcare staff presented similar psychological symptoms, including anxiety, fear, distress, and depression, which may lead to stress-related complications such as insomnia. In patients, these psychological impairments can be contributed to by being quarantined, perceptions of threats to life, and uncertainty about health status. Quarantine is also a factor for distress among healthcare staff, together with their heavy workload, the fear that they and their families would become infected, witnessing their patients’ poor and deteriorating conditions, and the requirement to wear protective gear. Strategies that are needed to address these factors include providing counselling services, implementing mindfulness-based therapies and optimism interventions, and providing telecommunication facilities for patients to communicate with their families. Healthcare staff should also be provided with these services, together with appropriate and flexible work shift arrangements and morale boosting. These strategies would improve not only the mental well-being of patients and healthcare staff, but also the self-efficacy and competence of the staff to provide quality healthcare services.
Multifactorial 10-Year Prior Diagnosis Prediction Model of Dementia
Authors: Dallora Ana Luiza , Minku Leandro , Mendes Emilia , Rennemark Mikael , Anderberg Peter , Sanmartin Berglund Johan
Published: September 2020

Dementia is a neurodegenerative disorder that affects the older adult population. To date, no cure or treatment to change its course is available. Since changes in the brains of affected individuals could be evidenced as early as 10 years before the onset of symptoms, prognosis research should consider this time frame. This study investigates a broad decision tree multifactorial approach for the prediction of dementia, considering 75 variables regarding demographic, social, lifestyle, medical history, biochemical tests, physical examination, psychological assessment and health instruments. Previous work on dementia prognoses with machine learning did not consider a broad range of factors in a large time frame. The proposed approach investigated predictive factors for dementia and possible prognostic subgroups. This study used data from the ongoing multipurpose Swedish National Study on Aging and Care, consisting of 726 subjects (91 presented dementia diagnosis in 10 years). The proposed approach achieved an AUC of 0.745 and Recall of 0.722 for the 10-year prognosis of dementia. Most of the variables selected by the tree are related to modifiable risk factors; physical strength was important across all ages. Also, there was a lack of variables related to health instruments routinely used for the dementia diagnosis.
Green Open Innovation Activities and Green Co-Innovation Performance in Taiwan’s Manufacturing Sector
Authors: Chang Ching-Hsun
Published: September 2020

This study investigates the positive effects of an appropriability regime and perceived similarity to green co-innovation performance when considering green open innovation activities as the mediator. It proposes a novel construct, i.e., green open innovation activities, and employs structural equation modeling to test its hypotheses. 190 valid questionnaires were collected from executives in Taiwanese manufacturing companies. Manufacturing activities are regarded as a major source of pollution. Consequently, given the broad concern for the environment among governments and consumers, adopting green practices has become critical for manufacturing companies. All the proposed hypotheses were supported by the analysis results. An appropriability regime is positively associated with green open innovation activities and green co-innovation performance. Perceived similarity is positively associated with green open innovation activities and green co-innovation performance. Moreover, green open innovation activities are positively associated with green co-innovation performance. A major finding is that if a company introduces one, the longer the duration of a green project is, the stronger the green open innovation activities and green co-innovation performance are. This study aimed to determine the simultaneous effects of both factors, i.e., appropriability regime, and perceived similarity on green open innovation activities and green co-innovation performance. The contribution of this study highlights the simultaneous importance of appropriability regimes and perceived similarity to determine a company’s green practices. While companies have tended to increase their green co-innovation performance, they need to improve their appropriability regime, perceived similarity, and green open innovation activities.
Lysenko and the Screwworm Fly—When Politics Interferes with Science and Public Health
Authors: Brisola Marcondes Carlos , Canale Angelo , Benelli Giovanni
Published: September 2020

In the One Health scenario, a deep understanding of the dynamics potentially threatening the development and implementation of useful pest and vector management tools is of key importance. The New World screwworm fly, Cochliomyia hominivorax (Coquerel) (Diptera: Calliphoridae), is characterized by a wide host range. It acts as an important agent of myiasis in humans and warm-blooded animals in the Neotropics, and has been eliminated from a wide region through genetic methods. Of note, Serebrovsky had already proposed in 1940 the principles of autocidal control by the translocation of segments between two chromosomes, but his work was negated by Lysenko, based on the negation of Mendelian genetics. This entomological case study emphasizes the danger of politics interfering with science, a still contemporary hot issue. The negation of global warming or current pandemics are further examples of this noxious influence.
Neurological Complications of COVID-19 and Possible Neuroinvasion Pathways: A Systematic Review
Authors: Orrù Graziella , Conversano Ciro , Malloggi Eleonora , Francesconi Francesca , Ciacchini Rebecca , Gemignani Angelo
Published: September 2020

The Coronavirus Disease 2019 (COVID-19) outbreak has shocked the whole world with its unexpected rapid spread. The virus responsible for the disease, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), enters host cells by means of the envelope spike protein, which binds to angiotensin-converting enzyme 2 receptors. These receptors are highly expressed in heart, lungs, respiratory tract epithelium, endothelial cells and brain. Since an increasing body of significant evidence is highlighting a possible neuroinvasion related to SARS-CoV-2, a state of the art on the neurological complications is needed. To identify suitable publications, our systematic review was carried out by searching relevant studies on PubMed and Scopus databases. We included studies investigating neurologic manifestations of SARS-CoV-2 in patients over 18. According to the analyzed studies, the most frequent disorders affecting central nervous system (CNS) seem to be the following: olfactory and taste disorders, ischemic/hemorrhagic stroke, meningoencephalitis and encephalopathy, including acute necrotizing encephalopathy, a rare type of encephalopathy. As regards the peripheral nervous system (PNS), Guillain-Barré and Miller Fisher syndromes are the most frequent manifestations reported in the literature. Important clinical information on the neurological manifestations of SARS-CoV-2 would help clinicians raise awareness and simultaneously improve the prognosis of critically ill patients.
National Disaster Management System: COVID-19 Case in Korea
Authors: Kim Junic , Ashihara Kelly
Published: September 2020

The COVID-19 pandemic poses unprecedented challenges for governments and societies around the world and represents a global crisis of hitherto unexperienced proportions. Our research seeks to analyse disaster management systems from a national perspective by examining the Korean management of the COVID-19 crisis according to a four-phase epidemiological disaster management system. Utilising a meta-study, official documents, reports and interviews, we explore the role of the control tower mechanism related to the life-cycle of disaster management, and Korea’s sustainable containment strategy. This study begins with a discussion of the crisis and disaster management literature and provides specific information related to the Korean government’s response to COVID-19. It continues by detailing specific strategies such as wide-spread testing, tracking, treatment and quarantine that have enabled Korea to prevent wide-spread community transmission. The study concludes emphasising the relevance of systematic national disaster management, providing insight into methods for containment in Korea – a system commended by the WHO. Implications include the extension and the efficient application of disaster management theory by empirical application and integration of concepts.
MuRF1/TRIM63, Master Regulator of Muscle Mass
Authors: Peris-Moreno Dulce , Taillandier Daniel , Polge Cécile
Published: September 2020

The E3 ubiquitin ligase MuRF1/TRIM63 was identified 20 years ago and suspected to play important roles during skeletal muscle atrophy. Since then, numerous studies have been conducted to decipher the roles, molecular mechanisms and regulation of this enzyme. This revealed that MuRF1 is an important player in the skeletal muscle atrophy process occurring during catabolic states, making MuRF1 a prime candidate for pharmacological treatments against muscle wasting. Indeed, muscle wasting is an associated event of several diseases (e.g., cancer, sepsis, diabetes, renal failure, etc.) and negatively impacts the prognosis of patients, which has stimulated the search for MuRF1 inhibitory molecules. However, studies on MuRF1 cardiac functions revealed that MuRF1 is also cardioprotective, revealing a yin and yang role of MuRF1, being detrimental in skeletal muscle and beneficial in the heart. This review discusses data obtained on MuRF1, both in skeletal and cardiac muscles, over the past 20 years, regarding the structure, the regulation, the location and the different functions identified, and the first inhibitors reported, and aim to draw the picture of what is known about MuRF1. The review also discusses important MuRF1 characteristics to consider for the design of future drugs to maintain skeletal muscle mass in patients with different pathologies.
Prion Protein at the Leading Edge: Its Role in Cell Motility
Authors: Prado Mariana Brandão , Melo Escobar Maria Isabel , Alves Rodrigo Nunes , Coelho Bárbara Paranhos , Fernandes Camila Felix de Lima , Boccacino Jacqueline Marcia , Iglesia Rebeca Piatniczka , Lopes Marilene Hohmuth
Published: September 2020

Cell motility is a central process involved in fundamental biological phenomena during embryonic development, wound healing, immune surveillance, and cancer spreading. Cell movement is complex and dynamic and requires the coordinated activity of cytoskeletal, membrane, adhesion and extracellular proteins. Cellular prion protein (PrPC) has been implicated in distinct aspects of cell motility, including axonal growth, transendothelial migration, epithelial–mesenchymal transition, formation of lamellipodia, and tumor migration and invasion. The preferential location of PrPC on cell membrane favors its function as a pivotal molecule in cell motile phenotype, being able to serve as a scaffold protein for extracellular matrix proteins, cell surface receptors, and cytoskeletal multiprotein complexes to modulate their activities in cellular movement. Evidence points to PrPC mediating interactions of multiple key elements of cell motility at the intra- and extracellular levels, such as integrins and matrix proteins, also regulating cell adhesion molecule stability and cell adhesion cytoskeleton dynamics. Understanding the molecular mechanisms that govern cell motility is critical for tissue homeostasis, since uncontrolled cell movement results in pathological conditions such as developmental diseases and tumor dissemination. In this review, we discuss the relevant contribution of PrPC in several aspects of cell motility, unveiling new insights into both PrPC function and mechanism in a multifaceted manner either in physiological or pathological contexts.
The New Paradigm of Network Medicine to Analyze Breast Cancer Phenotypes
Authors: Grimaldi Anna Maria , Conte Federica , Pane Katia , Fiscon Giulia , Mirabelli Peppino , Baselice Simona , Giannatiempo Rosa , Messina Francesco , Franzese Monica , Salvatore Marco , Paci Paola , Incoronato Mariarosaria
Published: September 2020

Breast cancer (BC) is a heterogeneous and complex disease as witnessed by the existence of different subtypes and clinical characteristics that poses significant challenges in disease management. The complexity of this tumor may rely on the highly interconnected nature of the various biological processes as stated by the new paradigm of Network Medicine. We explored The Cancer Genome Atlas (TCGA)-BRCA data set, by applying the network-based algorithm named SWItch Miner, and mapping the findings on the human interactome to capture the molecular interconnections associated with the disease modules. To characterize BC phenotypes, we constructed protein–protein interaction modules based on “hub genes”, called switch genes, both common and specific to the four tumor subtypes. Transcriptomic profiles of patients were stratified according to both clinical (immunohistochemistry) and genetic (PAM50) classifications. 266 and 372 switch genes were identified from immunohistochemistry and PAM50 classifications, respectively. Moreover, the identified switch genes were functionally characterized to select an interconnected pathway of disease genes. By intersecting the common switch genes of the two classifications, we selected a unique signature of 28 disease genes that were BC subtype-independent and classification subtype-independent. Data were validated both in vitro (10 BC cell lines) and ex vivo (66 BC tissues) experiments. Results showed that four of these hub proteins (AURKA, CDC45, ESPL1, and RAD54L) were over-expressed in all tumor subtypes. Moreover, the inhibition of one of the identified switch genes (AURKA) similarly affected all BC subtypes. In conclusion, using a network-based approach, we identified a common BC disease module which might reflect its pathological signature, suggesting a new vision to face with the disease heterogeneity.
Agonist Binding and G Protein Coupling in Histamine H2 Receptor: A Molecular Dynamics Study
Authors: Conrad Marcus , Söldner Christian A. , Miao Yinglong , Sticht Heinrich
Published: September 2020

The histamine H2 receptor (H2R) plays an important role in the regulation of gastric acid secretion. Therefore, it is a main drug target for the treatment of gastroesophageal reflux or peptic ulcer disease. However, there is as of yet no 3D-structural information available hampering a mechanistic understanding of H2R. Therefore, we created a model of the histamine-H2R-Gs complex based on the structure of the ternary complex of the β2-adrenoceptor and investigated the conformational stability of this active GPCR conformation. Since the physiologically relevant motions with respect to ligand binding and conformational changes of GPCRs can only partly be assessed on the timescale of conventional MD (cMD) simulations, we also applied metadynamics and Gaussian accelerated molecular dynamics (GaMD) simulations. A multiple walker metadynamics simulation in combination with cMD was applied for the determination of the histamine binding mode. The preferential binding pose detected is in good agreement with previous data from site directed mutagenesis and provides a basis for rational ligand design. Inspection of the H2R-Gs interface reveals a network of polar interactions that may contribute to H2R coupling selectivity. The cMD and GaMD simulations demonstrate that the active conformation is retained on a μs-timescale in the ternary histamine-H2R-Gs complex and in a truncated complex that contains only Gs helix α5 instead of the entire G protein. In contrast, histamine alone is unable to stabilize the active conformation, which is in line with previous studies of other GPCRs.
Host Synthesized Carbohydrate Antigens on Viral Glycoproteins as “Achilles’ Heel” of Viruses Contributing to Anti-Viral Immune Protection
Authors: Galili Uri
Published: September 2020

The glycans on enveloped viruses are synthesized by host-cell machinery. Some of these glycans on zoonotic viruses of mammalian reservoirs are recognized by human natural antibodies that may protect against such viruses. These antibodies are produced mostly against carbohydrate antigens on gastrointestinal bacteria and fortuitously, they bind to carbohydrate antigens synthesized in other mammals, neutralize and destroy viruses presenting these antigens. Two such antibodies are: anti-Gal binding to α-gal epitopes synthesized in non-primate mammals, lemurs, and New World monkeys, and anti-N-glycolyl neuraminic acid (anti-Neu5Gc) binding to N-glycolyl-neuraminic acid (Neu5Gc) synthesized in apes, Old World monkeys, and many non-primate mammals. Anti-Gal appeared in Old World primates following accidental inactivation of the α1,3galactosyltransferase gene 20–30 million years ago. Anti-Neu5Gc appeared in hominins following the inactivation of the cytidine-monophosphate-N-acetyl-neuraminic acid hydroxylase gene, which led to the loss of Neu5Gc <6 million-years-ago. It is suggested that an epidemic of a lethal virus eliminated ancestral Old World-primates synthesizing α-gal epitopes, whereas few mutated offspring lacking α-gal epitopes and producing anti-Gal survived because anti-Gal destroyed viruses presenting α-gal epitopes, following replication in parental populations. Similarly, anti-Neu5Gc protected few mutated hominins lacking Neu5Gc in lethal virus epidemics that eliminated parental hominins synthesizing Neu5Gc. Since α-gal epitopes are presented on many zoonotic viruses it is suggested that vaccines elevating anti-Gal titers may be of protective significance in areas endemic for such zoonotic viruses. This protection would be during the non-primate mammal to human virus transmission, but not in subsequent human to human transmission where the virus presents human glycans. In addition, production of viral vaccines presenting multiple α-gal epitopes increases their immunogenicity because of effective anti-Gal-mediated targeting of vaccines to antigen presenting cells for extensive uptake of the vaccine by these cells.
Influence of the Casting Concentration on the Mechanical and Optical Properties of FA/CaCl2-Derived Silk Fibroin Membranes
Authors: Kopp Alexander , Schunck Laura , Gosau Martin , Smeets Ralf , Burg Simon , Fuest Sandra , Kröger Nadja , Zinser Max , Krohn Sebastian , Behbahani Mehdi , Köpf Marius , Lauts Lisa , Rutkowski Rico
Published: September 2020

In this study, we describe the manufacturing and characterization of silk fibroin membranes derived from the silkworm Bombyx mori. To date, the dissolution process used in this study has only been researched to a limited extent, although it entails various potential advantages, such as reduced expenses and the absence of toxic chemicals in comparison to other conventional techniques. Therefore, the aim of this study was to determine the influence of different fibroin concentrations on the process output and resulting membrane properties. Casted membranes were thus characterized with regard to their mechanical, structural and optical assets via tensile testing, SEM, light microscopy and spectrophotometry. Cytotoxicity was evaluated using BrdU, XTT, and LDH assays, followed by live–dead staining. The formic acid (FA) dissolution method was proven to be suitable for the manufacturing of transparent and mechanically stable membranes. The fibroin concentration affects both thickness and transparency of the membranes. The membranes did not exhibit any signs of cytotoxicity. When compared to other current scientific and technical benchmarks, the manufactured membranes displayed promising potential for various biomedical applications. Further research is nevertheless necessary to improve reproducible manufacturing, including a more uniform thickness, less impurity and physiological pH within the membranes.
Toll-Like Receptor as a Potential Biomarker in Renal Diseases
Authors: Mertowski Sebastian , Lipa Paulina , Morawska Izabela , Niedźwiedzka-Rystwej Paulina , Bębnowska Dominika , Hrynkiewicz Rafał , Grywalska Ewelina , Roliński Jacek , Załuska Wojciech
Published: September 2020

One of the major challenges faced by modern nephrology is the identification of biomarkers associated with histopathological patterns or defined pathogenic mechanisms that may assist in the non-invasive diagnosis of kidney disease, particularly glomerulopathy. The identification of such molecules may allow prognostic subgroups to be established based on the type of disease, thereby predicting response to treatment or disease relapse. Advances in understanding the pathogenesis of diseases, such as membranous nephropathy, minimal change disease, focal segmental glomerulosclerosis, IgA (immunoglobulin A) nephropathy, and diabetic nephropathy, along with the progressive development and standardization of plasma and urine proteomics techniques, have facilitated the identification of an increasing number of molecules that may be useful for these purposes. The growing number of studies on the role of TLR (toll-like receptor) receptors in the pathogenesis of kidney disease forces contemporary researchers to reflect on these molecules, which may soon join the group of renal biomarkers and become a helpful tool in the diagnosis of glomerulopathy. In this article, we conducted a thorough review of the literature on the role of TLRs in the pathogenesis of glomerulopathy. The role of TLR receptors as potential marker molecules for the development of neoplastic diseases is emphasized more and more often, as prognostic factors in diseases on several epidemiological backgrounds.
Functional Characterization of Temporin-SHe, a New Broad-Spectrum Antibacterial and Leishmanicidal Temporin-SH Paralog from the Sahara Frog (Pelophylax saharicus)
Authors: André Sonia , Raja Zahid , Humblot Vincent , Piesse Christophe , Foulon Thierry , Sereno Denis , Oury Bruno , Ladram Ali
Published: September 2020

Amphibian skin is a promising natural resource for antimicrobial peptides (AMPs), key effectors of innate immunity with attractive therapeutic potential to fight antibiotic-resistant pathogens. Our previous studies showed that the skin of the Sahara Frog (Pelophylax saharicus) contains broad-spectrum AMPs of the temporin family, named temporins-SH. Here, we focused our study on temporin-SHe, a temporin-SHd paralog that we have previously identified in this frog but was never structurally and functionally characterized. We synthesized and determined the structure of temporin-SHe. This non-amphipathic α-helical peptide was demonstrated to strongly destabilize the lipid chain packing of anionic multilamellar vesicles mimicking bacterial membranes. Investigation of the antimicrobial activity revealed that temporin-SHe targets Gram-negative and Gram-positive bacteria, including clinical isolates of multi-resistant Staphylococcus aureus strains. Temporin-SHe exhibited also antiparasitic activity toward different Leishmania species responsible for visceral leishmaniasis, as well as cutaneous and mucocutaneous forms. Functional assays revealed that temporin-SHe exerts bactericidal effects with membrane depolarization and permeabilization, via a membranolytic mechanism observed by scanning electron microscopy. Temporin-SHe represents a new member of the very limited group of antiparasitic temporins/AMPs. Despite its cytotoxicity, it is nevertheless an interesting tool to study the AMP antiparasitic mechanism and design new antibacterial/antiparasitic agents.
Can miRNAs Be Considered as Diagnostic and Therapeutic Molecules in Ischemic Stroke Pathogenesis?—Current Status
Authors: Bulygin Kirill V. , Beeraka Narasimha M. , Saitgareeva Aigul R. , Nikolenko Vladimir N. , Gareev Ilgiz , Beylerli Ozal , Akhmadeeva Leila R. , Mikhaleva Liudmila M. , Torres Solis Luis Fernando , Solís Herrera Arturo , Avila-Rodriguez Marco F. , Somasundaram Siva G. , Kirkland Cecil E. , Aliev Gjumrakch
Published: September 2020

Ischemic stroke is one of the leading causes of death worldwide. Clinical manifestations of stroke are long-lasting and causing economic burden on the patients and society. Current therapeutic modalities to treat ischemic stroke (IS) are unsatisfactory due to the intricate pathophysiology and poor functional recovery of brain cellular compartment. MicroRNAs (miRNA) are endogenously expressed small non-coding RNA molecules, which can act as translation inhibitors and play a pivotal role in the pathophysiology associated with IS. Moreover, miRNAs may be used as potential diagnostic and therapeutic tools in clinical practice; yet, the complete role of miRNAs is enigmatic during IS. In this review, we explored the role of miRNAs in the regulation of stroke risk factors viz., arterial hypertension, metabolic disorders, and atherosclerosis. Furthermore, the role of miRNAs were reviewed during IS pathogenesis accompanied by excitotoxicity, oxidative stress, inflammation, apoptosis, angiogenesis, neurogenesis, and Alzheimer’s disease. The functional role of miRNAs is a double-edged sword effect in cerebral ischemia as they could modulate pathological mechanisms associated with risk factors of IS. miRNAs pertaining to IS pathogenesis could be potential biomarkers for stroke; they could help researchers to identify a particular stroke type and enable medical professionals to evaluate the severity of brain injury. Thus, ascertaining the role of miRNAs may be useful in deciphering their diagnostic role consequently it is plausible to envisage a suitable therapeutic modality against IS.
Deep Learning-Assisted High-Throughput Analysis of Freeze-Fracture Replica Images Applied to Glutamate Receptors and Calcium Channels at Hippocampal Synapses
Authors: Kleindienst David , Montanaro Jacqueline , Bhandari Pradeep , Case Matthew J. , Fukazawa Yugo , Shigemoto Ryuichi
Published: September 2020

The molecular anatomy of synapses defines their characteristics in transmission and plasticity. Precise measurements of the number and distribution of synaptic proteins are important for our understanding of synapse heterogeneity within and between brain regions. Freeze–fracture replica immunogold electron microscopy enables us to analyze them quantitatively on a two-dimensional membrane surface. Here, we introduce Darea software, which utilizes deep learning for analysis of replica images and demonstrate its usefulness for quick measurements of the pre- and postsynaptic areas, density and distribution of gold particles at synapses in a reproducible manner. We used Darea for comparing glutamate receptor and calcium channel distributions between hippocampal CA3-CA1 spine synapses on apical and basal dendrites, which differ in signaling pathways involved in synaptic plasticity. We found that apical synapses express a higher density of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and a stronger increase of AMPA receptors with synaptic size, while basal synapses show a larger increase in N-methyl-D-aspartate (NMDA) receptors with size. Interestingly, AMPA and NMDA receptors are segregated within postsynaptic sites and negatively correlated in density among both apical and basal synapses. In the presynaptic sites, Cav2.1 voltage-gated calcium channels show similar densities in apical and basal synapses with distributions consistent with an exclusion zone model of calcium channel-release site topography.
Activate or Inhibit? Implications of Autophagy Modulation as a Therapeutic Strategy for Alzheimer’s Disease
Authors: Krishnan Sharmeelavathi , Shrestha Yasaswi , Jayatunga Dona P. W. , Rea Sarah , Martins Ralph , Bharadwaj Prashant
Published: September 2020

Neurodegenerative diseases result in a range of conditions depending on the type of proteinopathy, genes affected or the location of the degeneration in the brain. Proteinopathies such as senile plaques and neurofibrillary tangles in the brain are prominent features of Alzheimer’s disease (AD). Autophagy is a highly regulated mechanism of eliminating dysfunctional organelles and proteins, and plays an important role in removing these pathogenic intracellular protein aggregates, not only in AD, but also in other neurodegenerative diseases. Activating autophagy is gaining interest as a potential therapeutic strategy for chronic diseases featuring protein aggregation and misfolding, including AD. Although autophagy activation is a promising intervention, over-activation of autophagy in neurodegenerative diseases that display impaired lysosomal clearance may accelerate pathology, suggesting that the success of any autophagy-based intervention is dependent on lysosomal clearance being functional. Additionally, the effects of autophagy activation may vary significantly depending on the physiological state of the cell, especially during proteotoxic stress and ageing. Growing evidence seems to favour a strategy of enhancing the efficacy of autophagy by preventing or reversing the impairments of the specific processes that are disrupted. Therefore, it is essential to understand the underlying causes of the autophagy defect in different neurodegenerative diseases to explore possible therapeutic approaches. This review will focus on the role of autophagy during stress and ageing, consequences that are linked to its activation and caveats in modulating this pathway as a treatment.
Measuring IGF-1 and IGFBP-3 Profiles in Women Seeking Assisted Reproduction; Relationship to Clinical Parameters (Study 1)
Authors: Yovich John L. , Zaidi Syeda , Nguyen Minh D. K. , Hinchliffe Peter M.
Published: September 2020

This study examines the IGF serum profile (IGF-1, IGFBP-3 and the IGF Ratio) from 1633 women who undertook an Assessment Cycle prior to any treatment by assisted reproduction. The idea is to progressively study the IGF profile with a view to identify those women who may be classified as having adult growth hormone deficiency (AGHD) and who may benefit from specific dynamic endocrinological testing to identify a potential benefit from growth hormone adjuvant treatment. This first study evaluates the IGF profile on clinical parameters, namely age, body mass index (BMI) and stature. The study shows a significant linear reduction in IGF-1 levels across the four age groups (<35 years, 35–39 years, 40–44 years and ≥45 years; p < 0.001). However, there was no variation in IGFBP-3 levels but the IGF Ratio showed a progressive linear elevation with advancing age (p < 0.001). With respect to both BMI and stature, none of the IGF profile parameters showed any variation. We conclude that further studies are warranted to examine the notion of underlying AGHD in the causation of the well-known feature of age-related poor prognosis in assisted reproduction.
Bone Loss in Distal Radial Fractures Treated with A Composite Xenohybrid Bone Substitute: A Two Years Follow-Up Retrospective Study
Authors: Ferracini Riccardo , Bistolfi Alessandro , Guidotti Claudio , Artiaco Stefano , Battista Agnese , Battiston Bruno , Perale Giuseppe
Published: September 2020

(1) Background: Recently, surgical treatment of distal radius fractures has increased exponentially. Many locking plates’ fixation systems have been developed allowing a more stable reduction and early mobilization. Sometimes, open reduction and fixation of distal radius fractures may leave a residual bone loss requiring grafting. This retrospective study reports clinical and radiologic outcomes of distal radius fractures treated with xenohybrid bone grafting in order to assess (i) the safety of the investigated bone graft; (ii) its radiological integration and biomechanical performances, and (iii) clinical outcomes of the patients; (2) Methods: We performed a retrospective study on a cohort of 19 patients. Preoperative X-ray and CT scan were performed. The mean clinical and radiographical follow-up was two years. Safety of the xenohybrid bone graft was constantly evaluated. Clinical results were assessed through the DASH score and Mayo wrist score; (3) Results: No adverse reactions, infections, and local or general complication were related to the use of xenohybrid bone graft. The radiolucency of the xenografts suggested progressive osteointegration. No evidence of bone graft resorption was detected. All the patients reached consolidation with good to excellent clinical results; and (4) Conclusions: Clinical and radiological data demonstrated that xenohybrid bone grafting promotes new bone formation and healing in osteopenic areas caused by fracture reduction.
PCM Cement-Lime Mortars for Enhanced Energy Efficiency of Multilayered Building Enclosures under Different Climatic Conditions
Authors: Guardia Cynthia , Barluenga Gonzalo , Palomar Irene
Published: September 2020

Phase change materials (PCMs) are promising materials for the energy efficiency improvement of building enclosures, due to their energy storage capacity. The thermal behaviour of a multi-layered building enclosure with five different compositions of PCM cement-lime mortars was evaluated under heating and cooling cycles. The behaviour of cement-lime mortars with 20% of microencapsulated PCM mixed with other additions, such as cellulose fibres and perlite, a lightweight aggregate (LWA), were studied under climate conditions of 15 °C–82% RH (cooling) and 30 °C–33% RH (heating) that were applied with a climatic chamber. Temperature and heat flux on both sides of the multi-layered enclosure were experimentally measured in laboratory tests. Temperature was also measured on both sides of the PCM cement-lime mortar layer. It was observed that the addition of the PCM cement-lime mortar layer delayed the heat flux through the enclosure. During a heating cycle, the incorporation of PCM delayed the arrival of the heat wave front by 30 min (8.1% compared to the reference mortar without PCM). The delay of the arrival of the heat wave front during the cooling cycle after adding PCM, compared to the reference mixture, reached 40.6% (130 min of delay). Furthermore, the incorporation of LWA in PCM cement-lime mortars also improved thermal insulation, further increasing energy efficiency of the building enclosure, and can be used not only for new buildings but also for energy rehabilitation of existing building enclosures.
Recent Development in Micromanufacturing of Metallic Materials
Authors: Zhao Jingwei , Jiang Zhengyi , Dobrzański Leszek A. , Lee Chong Soo , Yu Fuxiao
Published: September 2020

Product miniaturization is a trend for facilitating product usage, enabling product functions to be implemented in microscale geometries, and aimed at reducing product weight, volume, cost and pollution. Driven by ongoing miniaturization in diverse areas including medical devices, precision equipment, communication devices, micro-electromechanical systems (MEMS) and microsystems technology (MST), the demands for micro metallic products have increased tremendously. Such a trend requires development of advanced micromanufacturing technology of metallic materials for producing high-quality micro metallic products that possess excellent dimensional tolerances, required mechanical properties and improved surface quality. Micromanufacturing differs from conventional manufacturing technology in terms of materials, processes, tools, and machines and equipment, due to the miniaturization nature of the whole micromanufacturing system, which challenges the rapid development of micromanufacturing technology. Against such a background, the Special Issue “Micromanufacturing of Metallic Materials” was proposed to present the recent developments of micromanufacturing technologies of metallic materials. The papers collected in the Special Issue include research articles, literature review and technical notes, which have been highlighted in this editorial.
Dynamic Mechanical Properties and Visco-Elastic Damage Constitutive Model of Freeze–Thawed Concrete
Authors: Li Yan , Zhai Yue , Liang Wenbiao , Li Yubai , Dong Qi , Meng Fandong
Published: September 2020

To study the dynamic mechanical characteristics and constitutive relation of concrete materials under freeze–thaw (FT) cycle conditions, C35 concrete was taken as the research object in this paper, and FT tests were carried out with a freeze–thaw range of −20–20 °C and a freeze–thaw frequency up to 50 times. By using the separated Hopkinson pressure bar (SHPB) system, impact compression tests of concrete specimens under different FT cycle actions were developed, then the dynamic fracture morphology, fracture block distribution, stress–strain curve, peak stress and other dynamic mechanical properties of concrete were analyzed, and the influence law of FT action and strain rate was obtained. Through introducing the freeze–thaw deterioration damage factor and the stress damage variable, the dynamic visco-elastic damage constitutive equation of freeze–thawed concrete was constructed based on component combination theory. Furthermore, the damage evolution process and mechanism of freeze–thawed concrete materials were revealed. The research results show that the dynamic mechanical properties of concrete under a freeze–thaw environment are the combined results of the freeze–thaw deterioration effect and the strain rate strengthening effect. The dynamic visco-elastic damage constitutive model established in this paper can effectively describe the dynamic mechanical properties of freeze–thawed concrete, and has the characteristics of few parameters and good effect. The stress damage evolution path of concrete goes backward with the increase of FT cycles and the development speed gradually slows down. The greater the difference in FT cycles, the greater the difference in stress damage path.
Green Preparation of Aqueous Graphene Dispersion and Study on Its Dispersion Stability
Authors: Li Liangchuan , Zhou Ming , Jin Long , Mo Youtang , Xu Enyong , Chen Huajin , Liu Lincong , Wang Mingyue , Chen Xin , Zhu Hongwei
Published: September 2020

The large-scale preparation of stable graphene aqueous dispersion has been a challenge in the theoretical research and industrial applications of graphene. This study determined the suitable exfoliation agent for overcoming the van der Waals force between the layers of expanded graphite sheets using the liquid-phase exfoliation method on the basis of surface energy theory to prepare a single layer of graphene. To evenly and stably disperse graphene in pure water, the dispersants were selected based on Hansen solubility parameters, namely, hydrophilicity, heterocyclic structure and easy combinative features. The graphene exfoliation grade and the dispersion stability, number of layers and defect density in the dispersion were analysed under Tyndall phenomenon using volume sedimentation method, zeta potential analysis, scanning electron microscopy, Raman spectroscopy and atomic force microscopy characterization. Subsequently, the long-chain quaternary ammonium salt cationic surfactant octadecyltrimethylammonium chloride (0.3 wt.%) was electrolyzed in pure water to form ammonium ions, which promoted hydrogen bonding in the remaining oxygen-containing groups on the surface of the stripped graphene. Forming the electrostatic steric hindrance effect to achieve the stable dispersion of graphene in water can exfoliate a minimum of eight layers of graphene nanosheets; the average number of layers was less than 14. The 0.1 wt.% (sodium dodecylbenzene sulfonate: melamine = 1:1) mixed system forms π–π interaction and hydrogen bonding with graphene in pure water, which allow the stable dispersion of graphene for 22 days without sedimentation. The findings can be beneficial for the large-scale preparation of waterborne graphene in industrial applications.
Improving Corrosion Resistance of Aluminosilicate Refractories towards Molten Al-Mg Alloy Using Non-Wetting Additives: A Short Review
Authors: Barandehfard Faranak , Aluha James , Hekmat-Ardakan AliReza , Gitzhofer François
Published: September 2020

The corrosion of refractories in contact with high temperature aluminum-magnesium alloys leads to contamination of the Al-Mg alloy products by solid impurities from degraded refractories. Where both the spinel and corundum phases form in the refractories, cracks are generated and propagated by diffusion of molten Al-Mg, resulting in severe corrosion. In this review paper, the corrosion phenomenon is discussed, and published work is summarized, supplemented by our recent experimental results. Using the Alcan immersion test, materials based on white-fused mullite (WFM) were evaluated for their corrosion resistance and interfacial behavior. WFM was modified using different 2-wt.% of non-wetting additives (NWAs), such as BaSO4, CaF2, Secar®71 cement and wollastonite to improve their performance when in contact with molten Al-Mg alloy at 850 °C for 96 h. The mechanical properties of the samples such as flexural and compressive strength were evaluated, in addition to X-ray diffraction and microscopic analysis (optical and scanning electron microscopy coupled with X-ray elemental mapping). It was observed that cracks formed in samples were promoted with only BaSO4, CaF2, Secar®71 cement or wollastonite. However, cracks did not appear in the sample promoted with both 1-wt.% CaF2 and 1-wt.% BaSO4, because of improved anti-wetting properties in addition to inhibiting spinel (MgAl2O4) formation, which is the main cause of the cracks. This is a significant finding in the prevention of cracks and improvement of the refractory corrosion resistance.