bluuebunny/crossref_metadata_2025 huggingface dataset:
Delay-Based True Random Number Generator in Sub-Nanomillimeter IoT Devices
Authors: Randa Maulana , Samie Mohammad , Jennions Ian K.
Published: May 2020

True Random Number Generators (TRNGs) use physical phenomenon as their source of randomness. In electronics, one of the most popular structures to build a TRNG is constructed based on the circuits that form propagation delays, such as a ring oscillator, shift register, and routing paths. This type of TRNG has been well-researched within the current technology of electronics. However, in the future, where electronics will use sub-nano millimeter (nm) technology, the components become smaller and work on near-threshold voltage (NTV). This condition has an effect on the timing-critical circuit, as the distribution of the process variation becomes non-gaussian. Therefore, there is an urge to assess the behavior of the current delay-based TRNG system in sub-nm technology. In this paper, a model of TRNG implementation in sub-nm technology was created through the use of a specific Look-Up Table (LUT) in the Field-Programmable Gate Array (FPGA), known as SRL16E. The characterization of the TRNG was presented and it shows a promising result, in that the delay-based TRNG will work properly, with some constraints in sub-nm technology.
Characteristics of the Partial Discharge in the Development of Conductive Particle-Initiated Flashover of a GIS Insulator
Authors: Zhao Junping , An Zhengjie , Lv Bin , Wu Zhicheng , Zhang Qiaogen
Published: May 2020

Conductive particles are one of the most important defects which can greatly degrade the performance of gas-insulated metal-enclosed switchgear (GIS). Many efforts have been made to clarify the influence on the withstand voltage, understand the flashover mechanism, and build a comprehensive model to describe the particle-initiated flashover. In this study, a partial discharge (PD) signal detected through a photomultiplier (PMT) and recorded by a high-speed data acquisition (DAQ) system was used to analyze the discharge development of a conductive particle-contaminated GIS insulator under constant high AC voltage. An additional PMT was used as a reference to eliminate the dark count of the PMT and the data collection method of a DAQ system was optimized to capture the pulse waveform of each PD to obtain detailed physical information. Spectra of the PD pulse amplitude over pulse width, PD counts within various amplitude ranges over time and phase resolved partial discharge (PRPD) patterns of the PDs in different stages are obtained through the captured PD waveforms. Characteristics of the PDs from the application of the high AC voltage up to the flashover of the insulator were then analyzed, and it was found that the features of the PDs in the near-flashover stage were significantly different to the previous stages.
The Road toward Smart Cities: A Study of Citizens’ Acceptance of Mobile Applications for City Services
Authors: Hou Jinghui (Jove) , Arpan Laura , Wu Yijie , Feiock Richard , Ozguven Eren , Arghandeh Reza
Published: May 2020

Many local governments have started using smartphone applications to more effectively inform and communicate with citizens. This trend is of interest, as cities can only be smart if they are responsive to their citizens. In this paper, the intention to use such a mobile application among adult residents (n = 420) of a mid-sized city in the southeastern United States was examined using hierarchical linear regression analysis. The regression model that was tested indicated significant predictors of the intention to use the app in order to report municipal problems, such as power outages, and to request services for one’s home or community, including: Performance expectancy (e.g., citizens’ beliefs that the app would be efficient, helpful, convenient), effort expectancy (citizens’ beliefs about difficulty of using the app), social influence, perceived cost (e.g., privacy loss, storage space, unwanted notifications), and prior use of city apps. Consistent with current research on technology adoption, performance expectancy had the strongest influence on app-use intentions. Additionally, citizens’ trust in their city government’s ability to effectively manage an app was a weak, positive predictor of app-use intentions; general trust in the city government did not predict app-use intentions. Implications for city governments and city app developers are discussed.
Electricity Consumption Forecast Model Using Household Income: Case Study in Tanzania
Authors: Shibano Kyohei , Mogi Gento
Published: May 2020

When considering the electrification of a particular region in developing country, the electricity consumption in that region must be estimated. In sub-Saharan Africa, which is one of the areas with the lowest electrification rates in the world, the villages of minority groups are scattered over a vast area of land, so electrification using distributed generators is being actively studied. Specifically, constructing a microgrid or introducing a solar system to each household is being considered. In this case, the electricity consumption of each area needs to be estimated, then a system with enough capacity could be introduced. In this study, we propose a household income electricity consumption model to estimate the electricity consumption of a specific area. We first estimate the electricity consumption of each household based on income and the electricity consumption of a specific area can be derived by adding up them in that area. Through a case study in Tanzania, electricity consumption derived using this model was compared with electricity consumption published by TANESCO, and the validity of the model was verified. We forecasted the electricity consumption in each region using the household income electricity consumption model, and the average forecast accuracy was 74%. The accuracy was 87% when the electricity consumption in Tanzania mainland was forecasted by adding the predicted values.
A Coordination Mechanism For Reducing Price Spikes in Distribution Grids
Authors: Chakraborty Shantanu , Verzijlbergh Remco , Baker Kyri , Cvetkovic Milos , Vries Laurens De , Lukszo Zofia
Published: May 2020

Recently, given the increased integration of renewables and growing uncertainty in demand, the wholesale market price has become highly volatile. Energy communities connected to the main electricity grid may be exposed to this increasing price volatility. Additionally, they may also be exposed to local network congestions, resulting in price spikes. Motivated by this problem, in this paper, we present a coordination mechanism between entities at the distribution grid to reduce price volatility. The mechanism relies on the concept of duality theory in mathematical programming through which explicit constraints can be imposed on the local electricity price. Constraining the dual variable related to price enables the quantification of the demand-side flexibility required to guarantee a certain price limit. We illustrate our approach with a case study of a congested distribution grid and an energy storage system as the source of the required demand-side flexibility. Through detailed simulations, we determine the optimal size and operation of the storage system required to constrain prices. An economic evaluation of the case study shows that the business case for providing the contracted flexibility with the storage system depends strongly on the chosen price limit.
Replacement and Maintenance Decision Analysis for Hydraulic Machinery Facilities at Reservoirs under Imperfect Maintenance
Authors: Leu Sou-Sen , Ying Tao-Ming
Published: May 2020

After the long-term operation of reservoir facilities, they will become nonoperational due to the material deterioration and the performance degradation. One of crucial decisions is to determine the maintenance or replacement of the facilities in a cost-effective manner. Conventional replacement models seldom consider the maintenance effect. The facilities after maintenance are generally not as good as new, but are relatively restored. The target of this study is to establish a replacement decision model of the reservoir facilities under imperfect maintenance. By combining the theories of reliability analysis, imperfect maintenance, and engineering economics, the best timing of replacement that achieves cost-effectiveness is analyzed and proposed. Lastly, based on the design of experiments (DOE) and simulation, the regression curve chart for the economical replacement decision is established. Once the failure rate, the age of recovery after maintenance, and the ratio of maintenance cost to replacement cost are estimated based on historical data, the cost-effective replacement time of hydraulic machinery facilities will be efficiently determined.
Performance Comparison and Current Challenges of Using Machine Learning Techniques in Cybersecurity
Authors: Shaukat Kamran , Luo Suhuai , Varadharajan Vijay , Hameed Ibrahim , Chen Shan , Liu Dongxi , Li Jiaming
Published: May 2020

Cyberspace has become an indispensable factor for all areas of the modern world. The world is becoming more and more dependent on the internet for everyday living. The increasing dependency on the internet has also widened the risks of malicious threats. On account of growing cybersecurity risks, cybersecurity has become the most pivotal element in the cyber world to battle against all cyber threats, attacks, and frauds. The expanding cyberspace is highly exposed to the intensifying possibility of being attacked by interminable cyber threats. The objective of this survey is to bestow a brief review of different machine learning (ML) techniques to get to the bottom of all the developments made in detection methods for potential cybersecurity risks. These cybersecurity risk detection methods mainly comprise of fraud detection, intrusion detection, spam detection, and malware detection. In this review paper, we build upon the existing literature of applications of ML models in cybersecurity and provide a comprehensive review of ML techniques in cybersecurity. To the best of our knowledge, we have made the first attempt to give a comparison of the time complexity of commonly used ML models in cybersecurity. We have comprehensively compared each classifier’s performance based on frequently used datasets and sub-domains of cyber threats. This work also provides a brief introduction of machine learning models besides commonly used security datasets. Despite having all the primary precedence, cybersecurity has its constraints compromises, and challenges. This work also expounds on the enormous current challenges and limitations faced during the application of machine learning techniques in cybersecurity.
The Role of Energy Valuation of Agroforestry Biomass on the Circular Economy
Authors: Torreiro Yarima , Pérez Leticia , Piñeiro Gonzalo , Pedras Francisco , Rodríguez-Abalde Angela
Published: May 2020

The use of biomass has increased significantly in recent years. In this context, the use of not valued high-potential biomass (NVHPB) is emerging as a suitable alternative. This is the case of pruning vine, pruning kiwi, scrub (heather, gorse, broom) and forest pruning. The objective of this research was to study the potential of six selected agroforestry biomasses as biofuels in thermochemical processes. For that purpose, biomass was collected by specific machinery. Proximate and ultimate analyses were carried out as well as the inorganic compounds’ determination. Then, natural and forced drying were conducted. Low heating values (LHV) between 17 and 20 MJ/kg (dry basis) were achieved in all analyzed cases. Granulometric reduction, biomass classification and densification took place. Finally, energy recovery tests through microcogeneration were carried out. Values close to 97% in cogeneration efficiency were reached (9% net electric yield and 88% thermal yield), offering an alternative to obtain clean energy.
Antiedematogenic and Anti-Inflammatory Activity of the Monoterpene Isopulegol and Its β-Cyclodextrin (β-CD) Inclusion Complex in Animal Inflammation Models
Authors: Ramos Andreza Guedes Barbosa , de Menezes Irwin Rose Alencar , da Silva Maria Sanádia Alexandre , Torres Pessoa Renata , de Lacerda Neto Luiz Jardelino , Rocha Santos Passos Fabíola , Melo Coutinho Henrique Douglas , Iriti Marcello , Quintans-Júnior Lucindo José
Published: May 2020

Isopulegol (ISO) is an alcoholic monoterpene widely found in different plant species, such as Melissa officinalis, and has already been reported to have a number of pharmacological properties. Like other terpenes, ISO is a highly volatile compound that is slightly soluble in water, so its inclusion into cyclodextrins (CDs) is an interesting approach to increase its solubility and bioavailability. Thus, our aim was to evaluate the antiedematogenic and anti-inflammatory activity of isopulegol and a β-cyclodextrin–isopulegol inclusion complex (ISO/β-CD) in rodent models. For the anti-inflammatory activity evaluation, antiedematogenic plethysmometry and acute (peritonitis and pleurisy), as well as chronic (cotton pellet-induced granuloma) anti-inflammatory models, were used. The docking procedure is used to evaluate, analyze, and predict their binding mode of interaction with H1 and Cox-2 receptors. The animals (n = 6) were divided into groups: ISO and ISO/β-CD, negative control (saline), and positive control (indomethacin and promethazine). ISO and ISO/β-CD were able to reduce acute inflammatory activity by decreasing albumin extravasation, leukocyte migration, and MPO concentration, and reducing exudate levels of IL-1β and TNF-α. ISO and ISO/β-CD significantly inhibited edematogenic activity in carrageenan- and dextran-induced paw edema. Moreover, both significantly reduced chronic inflammatory processes, given the lower weight and protein concentration of granulomas in the foreign body granulomatous inflammation model. The results suggest that the inclusion of ISO in β-cyclodextrins improves its pharmacological properties, with the histamine and prostaglandin pathways as probable mechanisms of inhibition, and also reinforces the anti-inflammatory profile of this terpene.
Allergenicity of Deamidated and/or Peptide-Bond-Hydrolyzed Wheat Gliadin by Transdermal Administration
Authors: Abe Ryosuke , Matsukaze Narumi , Kobayashi Hayato , Yamaguchi Yusuke , Uto-Kondo Harumi , Kumagai Hitoshi , Kumagai Hitomi
Published: May 2020

Hydrochloric acid (HCl)-treated wheat protein (HWP) is widely used in various products, including foods, cosmetics and shampoos. Recently, immediate hypersensitivity towards facial soap containing HWP has been reported. HCl treatment of protein causes hydrolysis not only of main-chain amide bonds (peptide-bond hydrolysis) but also of side-chain ones (deamidation). We have already reported that gliadin, the main allergen in wheat, reduces allergenicity and increases digestibility by deamidation, indicating that deamidation and peptide-bond hydrolysis are effective to reduce the allergenicity of wheat protein. However, transdermally administered HWP is assumed to induce sensitization to orally administered wheat protein even in those who have been taking wheat products daily before sensitization. The present study was conducted to examine which structural change is responsible for the induction of cutaneous sensitization by comparing the allergenicity of deamidated and/or peptide-bond-hydrolyzed wheat gliadin. Because we have developed a deamidation method without causing peptide-bond hydrolysis, only deamidated wheat gliadin is available. Therefore, after deamidated-only, hydrolyzed-only, and deamidated and hydrolyzed gliadins were transdermally administered to mice for several weeks, the corresponding gliadin was intraperitoneally administered and allergenicity was evaluated. Transdermal administration of deamidated and hydrolyzed gliadin induced severe allergic reaction, while that of deamidated-only and hydrolyzed-only gliadin showed almost no allergic response. This result indicates that both deamidation and peptide-bond hydrolysis are necessary to increase the allergenic potency of transdermally administered wheat gliadin.
Masculinity, Intimacy, and Mourning: A Father’s Memoir of His Son Killed in Action in World War II
Authors: Ruxton Sandy
Published: May 2020

Emotional restraint was the norm for the bereaved during and after the Second World War. Displays of individual grief were discouraged, and overshadowed by a wider concern for mass bereavement. There is limited archival evidence of the suffering that fathers of sons killed in action endured. This article draws upon and analyses a powerful memoir written by my grandfather, lamenting the death of his only son killed in action near the end of the War. While most men contained their emotions in such circumstances, this extended lament expresses a range of deep feelings: Love and care for the departed son, tenderness towards other family members, guilt at sending his son away to boarding school, loss of faith in (Christian) religion, and a sense of worthlessness and personal failure. Of particular interest is the impact of geographical distance over which this narrative is played out, and what it reveals about the experience of one white British middle-class family living overseas, but strongly interconnected with ‘home’ (and specifically Scotland). It also documents the pain of prolonged absence as a result of war; often boys sent ‘home’ to board were separated from their parents for much of their childhood, and were forced to ‘become men’—but not as their parents had envisaged. The article concludes by exploring the implications of this private memoir and what it reveals about memoir, masculinity, and subjectivity; gender and grieving; connections with ‘home’; and constructing meaning after trauma.
The Contribution of Geophysics to the Knowledge of the Hidden Archaeological Heritage of Montenegro
Authors: Cozzolino Marilena , Baković Mile , Borovinić Nikola , Galli Giorgia , Gentile Vincenzo , Jabučanin Marija , Mauriello Paolo , Merola Pasquale , Živanović Miloš
Published: May 2020

Montenegro is a land of great history which needs attention and care for a deeper knowledge and its making at the disposal of new generations. It is still a territory to be discovered, studied, and disclosed. It is important to understand how much hidden heritage there is still in this area to explore and exploit, but on the other hand, how much known heritage exists to protect and monitor, preventing its destruction and loss. In this context, Montenegro is heavily investing in the management of cultural heritage through initiatives for identification, protection, preservation, enhancement and fruition of them. In the frame of the knowledge, the use of non-destructive geophysical methods can be helpful for a cognitive investigation immediately in the bud of any archaeological verification project, safeguarded through preventive archaeology operations and the exploration of large areas within archaeological parks. In this paper, the results of geophysical prospections at the Hellenistic-Illyrian site of Mjace, the roman towns of Doclea and Municipium S, the medieval city of Svač, and the Stećci medieval tombstones graveyards of Novakovići, Žugića, and Plužine are presented. The study allowed the reconnaissance of new buried structures in the soil and has provided an updated view of the rich archaeological heritage of Montenegro.
Integrating Land-Use and Renewable Energy Planning Decisions: A Technical Mapping Guide for Local Government
Authors: Guo Jiaao , Fast Victoria , Teri Philip , Calvert Kirby
Published: May 2020

Land-based, utility-scale renewable energy (RE) systems using wind or solar resources to generate electricity is becoming a decisive solution to meet long-term carbon emission reduction goals. Local governments are responding in kind, by adopting their own goals and/or establishing policies to facilitate successful implementations of RE in their jurisdiction. One factor to successful RE development is to locate the most suitable lands, while continuing to sustain land-based economies and ecosystem services. Local governments often have limited resources; and this is especially true for small, land-constrained local governments. In this paper, we illustrate how a standardized RE technical mapping framework can be used by local governments to advance the implementation of RE in land-constrained areas, through a case study in the Town of Canmore, Alberta. Canmore has a limited municipal area surrounded by the Canadian Rockies, along with complex land-use bylaw and environmentally sensitive habitats. This mapping framework accounts for these conditions as it considers theoretical resources, technically recoverable lands, legally accessible lands, and the spatial capital cost of connecting new RE facilities. Different land-use planning scenarios are considered including changing setback buffers and expanding restrictions on development to all environmentally sensitive districts. The total RE potentials are then estimated based on the least-conflict lands. Technically speaking, even under restrictive land suitability scenarios, Canmore holds enough land to achieve ambitious RE targets, but opportunities and challenges to implementation remain. To eventually succeed in its long-term emission reduction goal, the most decisive step for Canmore is to balance the growth of energy demands, land-use changes, and practicable RE development. Mapping systems that can study the influence of land-use planning decisions on RE potential are critical to achieving this balance.
Overview of Dual-Acting Drug Methotrexate in Different Neurological Diseases, Autoimmune Pathologies and Cancers
Authors: Koźmiński Przemysław , Halik Paweł Krzysztof , Chesori Raphael , Gniazdowska Ewa
Published: May 2020

Methotrexate, a structural analogue of folic acid, is one of the most effective and extensively used drugs for treating many kinds of cancer or severe and resistant forms of autoimmune diseases. In this paper, we take an overview of the present state of knowledge with regards to complex mechanisms of methotrexate action and its applications as immunosuppressive drug or chemotherapeutic agent in oncological combination therapy. In addition, the issue of the potential benefits of methotrexate in the development of neurological disorders in Alzheimer’s disease or myasthenia gravis will be discussed.
Eyeing the Extracellular Matrix in Vascular Development and Microvascular Diseases and Bridging the Divide between Vascular Mechanics and Function
Authors: Chaqour Brahim , Karrasch Charles
Published: May 2020

The extracellular matrix (ECM) is critical in all aspects of vascular development and health: supporting cell anchorage, providing structure, organization and mechanical stability, and serving as a sink for growth factors and sustained survival signals. Abnormal changes in ECM protein expression, organization, and/or properties, and the ensuing changes in vascular compliance affect vasodilator responses, microvascular pressure transmission, and collateral perfusion. The changes in microvascular compliance are independent factors initiating, driving, and/or exacerbating a plethora of microvascular diseases of the eye including diabetic retinopathy (DR) and vitreoretinopathy, retinopathy of prematurity (ROP), wet age-related macular degeneration (AMD), and neovascular glaucoma. Congruently, one of the major challenges with most vascular regenerative therapies utilizing localized growth factor, endothelial progenitor, or genetically engineered cell delivery, is the regeneration of blood vessels with physiological compliance properties. Interestingly, vascular cells sense physical forces, including the stiffness of their ECM, through mechanosensitive integrins, their associated proteins and the actomyosin cytoskeleton, which generates biochemical signals that culminate in a rapid expression of matricellular proteins such as cellular communication network 1 (CCN1) and CCN2 (aka connective tissue growth factor or CTGF). Loss or gain of function of these proteins alters genetic programs of cell growth, ECM biosynthesis, and intercellular signaling, that culminate in changes in cell behavior, polarization, and barrier function. In particular, the function of the matricellular protein CCN2/CTGF is critical during retinal vessel development and regeneration wherein new blood vessels form and invest a preformed avascular neural retina following putative gradients of matrix stiffness. These observations underscore the need for further in-depth characterization of the ECM-derived cues that dictate structural and functional properties of the microvasculature, along with the development of new therapeutic strategies addressing the ECM-dependent regulation of pathophysiological stiffening of blood vessels in ischemic retinopathies.
Deubiquitinating Enzymes in Coronaviruses and Possible Therapeutic Opportunities for COVID-19
Authors: Clemente Valentino , D’Arcy Padraig , Bazzaro Martina
Published: May 2020

Following the outbreak of novel severe acute respiratory syndrome (SARS)-coronavirus (CoV)2, the majority of nations are struggling with countermeasures to fight infection, prevent spread and improve patient survival. Considering that the pandemic is a recent event, no large clinical trials have been possible and since coronavirus specific drug are not yet available, there is no strong consensus on how to treat the coronavirus disease 2019 (COVID-19) associated viral pneumonia. Coronaviruses code for an important multifunctional enzyme named papain-like protease (PLP), that has many roles in pathogenesis. First, PLP is one of the two viral cysteine proteases, along with 3-chymotripsin-like protease, that is responsible for the production of the replicase proteins required for viral replication. Second, its intrinsic deubiquitinating and deISGylating activities serve to antagonize the host’s immune response that would otherwise hinder infection. Both deubiquitinating and deISGylating functions involve the removal of the small regulatory polypeptides, ubiquitin and ISG15, respectively, from target proteins. Ubiquitin modifications can regulate the innate immune response by affecting regulatory proteins, either by altering their stability via the ubiquitin proteasome pathway or by directly regulating their activity. ISG15 is a ubiquitin-like modifier with pleiotropic effects, typically expressed during the host cell immune response. PLP inhibitors have been evaluated during past coronavirus epidemics, and have showed promising results as an antiviral therapy in vitro. In this review, we recapitulate the roles of PLPs in coronavirus infections, report a list of PLP inhibitors and suggest possible therapeutic strategies for COVID-19 treatment, using both clinical and preclinical drugs.
Homo- and Hetero-Oligonuclear Complexes of Platinum Group Metals (PGM) Coordinated by Imine Schiff Base Ligands
Authors: Miroslaw Barbara
Published: May 2020

Chemistry of Schiff base (SB) ligands began in 1864 due to the discovery made by Hugo Schiff (Schiff, H., Justus Liebigs Ann. der Chemie 1864, 131 (1), 118–119). However, there is still a vivid interest in coordination compounds based on imine ligands. The aim of this paper is to review the most recent concepts on construction of homo- and hetero-oligonuclear Schiff base coordination compounds narrowed down to the less frequently considered complexes of platinum group metals (PGM). The combination of SB and PGM in oligonuclear entities has several advantages over mononuclear or polynuclear species. Such complexes usually exhibit better electroluminescent, magnetic and/or catalytic properties than mononuclear ones due to intermetallic interactions and frequently have better solubility than polymers. Various construction strategies of oligodentate imine ligands for coordination of PGM are surveyed including simple imine ligands, non-innocent 1,2-diimines, chelating imine systems with additional N/O/S atoms, classic N2O2-compartmental Schiff bases and their modifications resulting in acyclic fused ligands, macrocycles such as calixsalens, metallohelical structures, nano-sized molecular wheels and hybrid materials incorporating mesoionic species. Co-crystallization and formation of metallophilic interactions to extend the mononuclear entities up to oligonuclear coordination species are also discussed.
Inhalation Toxicology of Vaping Products and Implications for Pulmonary Health
Authors: Traboulsi Hussein , Cherian Mathew , Abou Rjeili Mira , Preteroti Matthew , Bourbeau Jean , Smith Benjamin M. , Eidelman David H. , Baglole Carolyn J.
Published: May 2020

E-cigarettes have a liquid that may contain flavors, solvents, and nicotine. Heating this liquid generates an aerosol that is inhaled into the lungs in a process commonly referred to as vaping. E-cigarette devices can also contain cannabis-based products including tetrahydrocannabinol (THC), the psychoactive component of cannabis (marijuana). E-cigarette use has rapidly increased among current and former smokers as well as youth who have never smoked. The long-term health effects are unknown, and emerging preclinical and clinical studies suggest that e-cigarettes may not be harmless and can cause cellular alterations analogous to traditional tobacco smoke. Here, we review the historical context and the components of e-cigarettes and discuss toxicological similarities and differences between cigarette smoke and e-cigarette aerosol, with specific reference to adverse respiratory outcomes. Finally, we outline possible clinical disorders associated with vaping on pulmonary health and the recent escalation of acute lung injuries, which led to the declaration of the vaping product use-associated lung injury (EVALI) outbreak. It is clear there is much about vaping that is not understood. Consequently, until more is known about the health effects of vaping, individual factors that need to be taken into consideration include age, current and prior use of combustible tobacco products, and whether the user has preexisting lung conditions such as asthma and chronic obstructive pulmonary disease (COPD).
Novel Cell-Based and Tissue Engineering Approaches for Induction of Angiogenesis as an Alternative Therapy for Diabetic Retinopathy
Authors: Jalilian Elmira , Elkin Kenneth , Shin Su Ryon
Published: May 2020

Diabetic retinopathy (DR) is the most frequent microvascular complication of long-term diabetes and the most common cause of blindness, increasing morbidity in the working-age population. The most effective therapies for these complications include laser photocoagulation and anti-vascular endothelial growth factor (VEGF) intravitreal injections. However, laser and anti-VEGF drugs are untenable as a final solution as they fail to address the underlying neurovascular degeneration and ischemia. Regenerative medicine may be a more promising approach, aimed at the repair of blood vessels and reversal of retinal ischemia. Stem cell therapy has introduced a novel way to reverse the underlying ischemia present in microvascular complications in diseases such as diabetes. The present review discusses current treatments, their side effects, and novel cell-based and tissue engineering approaches as a potential alternative therapeutic approach.
Epigenetic Alterations in Oesophageal Cancer: Expression and Role of the Involved Enzymes
Authors: Lopes Nair , Correia Margareta P. , Henrique Rui , Jerónimo Carmen
Published: May 2020

Oesophageal cancer is a life-threatening disease, accounting for high mortality rates. The poor prognosis of this malignancy is mostly due to late diagnosis and lack of effective therapies for advanced disease. Epigenetic alterations may constitute novel and attractive therapeutic targets, owing to their ubiquity in cancer and their reversible nature. Herein, we offer an overview of the most important studies which compared differences in expression of enzymes that mediate epigenetic alterations between oesophageal cancer and normal mucosa, as well as in vitro data addressing the role of these genes/proteins in oesophageal cancer. Furthermore, The Cancer Genome Atlas database was interrogated for the correlation between expression of these epigenetic markers and standard clinicopathological features. We concluded that most epigenetic players studied thus far are overexpressed in tumours compared to normal tissue. Furthermore, functional assays suggest an oncogenic role for most of those enzymes, supporting their potential as therapeutic targets in oesophageal cancer.
Cementless Oxford Medial Unicompartmental Knee Replacement—Clinical and Radiological Results of 228 Knees with a Minimum 2-Year Follow-Up
Authors: Panzram Benjamin , Mandery Mira , Reiner Tobias , Gotterbarm Tobias , Schiltenwolf Marcus , Merle Christian
Published: May 2020

(1) Background: Studies show several advantages of unicompartmental knee replacement (UKR) over total knee replacements (TKR), whereas registry based revision rates of UKR are significantly higher than for TKA. Registry data report lower revision rates for cementless UKR compared to cemented UKR. The aim of this study was to assess clinical and radiological results of cementless Oxford UKR (OUKR) in an independent cohort. (2) Methods: This retrospective cohort study examines a consecutive series of 228 cementless OUKR. Clinical outcome was measured using functional scores (Oxford Knee Score (OKS), American Knee Society Score (AKSS), Hannover Functional Ability Questionnaire for Osteoarthritis (FFbH-OA), range of motion (ROM)), pain and satisfaction. Radiographs were analyzed regarding the incidence of radiolucent lines (RL), implant positioning, and their possible impact on clinical outcome. (3) Results: At a mean follow-up of 37.1 months, the two and three year revision free survival-rates were 97.5% and 96.9%. Reasons for revision surgery were progression of osteoarthritis, inlay dislocation and pain. All clinical outcome scores showed a significant improvement from pre- to postoperative. The incidence of RL around the implant was highest within the first year postoperatively (36%), and decreased (5%) within the second year. Their presence was not correlated with inferior clinical outcome. Implant positioning showed no influence on clinical outcome. (4) Conclusion: Cementless OUKR showed excellent clinical outcome and survival rates, with reliable osteointegration. Neither the incidence of radiolucent lines nor implant positioning were associated with inferior clinical outcome.
Reduced and Normalized Carbohydrate Antigen 19-9 Concentrations after Neoadjuvant Chemotherapy Have Comparable Prognostic Performance in Patients with Borderline Resectable and Locally Advanced Pancreatic Cancer
Authors: Lee Woohyung , Park Yejong , Kwon Jae Woo , Jun Eunsung , Song Ki Byung , Lee Jae Hoon , Hwang Dae Wook , Yoo Changhoon , Kim Kyu-pyo , Jeong Jae Ho , Chang Heung-Moon , Ryoo Baek-Yeol , Park Seo Young , Kim Song Cheol
Published: May 2020

Background: The association between optimal carbohydrate antigen (CA) 19-9 concentration after neoadjuvant chemotherapy (NACT) and prognosis has not been confirmed in patients with borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC). Methods: This retrospective study included 122 patients with BRPC and 103 with LAPC who underwent surgery after NACT between 2012 and 2019 in a tertiary referral center. Prognostic models were established based on relative difference of the CA 19-9 (RDC), with their prognostic performance compared using C-index and Akaike information criterion (AIC). Results: CA 19-9 concentrations of 37–1000 U/mL before NACT showed prognostic significance in patients with BRPC and LAPC (hazard ratio [HR]: 0.262; 95% confidence interval [CI]: 0.092–0.748; p = 0.012). Prognostic models in this subgroup showed that RDC was independently prognostic of better overall survival (HR: 0.262; 95% CI: 0.093–0.739; p = 0.011) and recurrence free survival (HR: 0.299; 95% CI: 0.140–0.642; p = 0.002). The prognostic performances of RDC (C-index: 0.653; AIC: 227.243), normalization of CA 19-9 after NACT (C-index: 0.625; AIC: 230.897) and surgery (C-index: 0.613; AIC: 233.114) showed no significant differences. Conclusion: RDC was independently associated with better prognosis after NACT in patients with BRPC or LAPC. Decreased CA19-9 after NACT was a prognostic indicator of better survival and recurrence, as was normalization of CA 19-9 after both NACT and surgery.
Temporal Trends of Emergency Department Visits of Patients with Atrial Fibrillation: A Nationwide Population-Based Study
Authors: Lee So-Ryoung , Choi Eue-Keun , Lee Seo-Young , Lee Euijae , Han Kyung-Do , Cha Myung-Jin , Kwon Woon Yong , Shin Sang Do , Oh Seil , Lip Gregory Y. H.
Published: May 2020

We aimed to describe temporal trends in emergency department (ED) visits of patients with atrial fibrillation (AF) over 12 years. A repeated cross-sectional analysis of ED visits in AF patients using the Korean nationwide claims database between 2006 and 2017 were conducted. We identified AF patients who had ≥1 ED visits. The incidence of ED visits among total AF population, cause of ED visit, and clinical outcomes were evaluated. During 12 years, the annual numbers of AF patients who attended ED at least once a year continuously increased (40,425 to 99,763). However, the annual incidence of ED visits of AF patients was stationary at about 30% because the number of total AF patients also increased during the same period. The most common cause of ED visits was cerebral infarction. Although patients had a higher risk profile over time, the 30-day and 90-day mortality after ED visit decreased over time. ED visits due to ischemic stroke, intracranial hemorrhage, and myocardial infarction decreased, whereas ED visits due to AF, gastrointestinal bleeding, and other major bleeding slightly increased among total AF population over 12 years. A substantial proportion of AF patients attended ED every year, and the annual numbers of AF patients who visited the ED significantly increased over 12 years. Optimized management approaches in a holistic and integrated manner should be provided to reduce ED visits of AF patients.
Thoracic Ultrasound for Immediate Exclusion of Pneumothorax after Interventional Bronchoscopy
Authors: Eisenmann Stephan , Winantea Jane , Karpf-Wissel Rüdiger , Funke Faustina , Stenzel Elena , Taube Christian , Darwiche Kaid
Published: May 2020

Background. Pneumothorax is a common side effect in interventional pulmonology. The ideal moment for detection with chest X-ray or ultrasound has not yet been defined. Earlier studies demonstrated the utility of performing these tests with a certain delay, which always results in a potentially dangerous gap. Methods. We prospectively enrolled patients with pulmonary interventions at increased risk of pneumothorax. Thoracic ultrasound was performed immediately after the intervention and at the moment of chest X-ray with a delay up to two hours. Results: Overall, we detected four pneumothoraxes in 115 procedures. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 75%, 100%, 100%, 99%, 99% for ultrasound and 75%, 90%, 21%, 99% und 89% for chest X-ray respectively. All pneumothoraces requiring chest tube were sufficiently detected by both methods. Conclusion. Thoracic ultrasound when performed immediately can more accurately exclude pneumothorax after interventional bronchoscopy when compared to chest X-ray. Further ultrasound examinations are unnecessary.
Summary-Based Methylome-Wide Association Analyses Suggest Potential Genetically Driven Epigenetic Heterogeneity of Alzheimer’s Disease
Authors: Nazarian Alireza , Yashin Anatoliy , Kulminski Alexander
Published: May 2020

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with no curative treatment available. Exploring the genetic and non-genetic contributors to AD pathogenesis is essential to better understand its underlying biological mechanisms, and to develop novel preventive and therapeutic strategies. We investigated potential genetically driven epigenetic heterogeneity of AD through summary data-based Mendelian randomization (SMR), which combined results from our previous genome-wide association analyses with those from two publicly available methylation quantitative trait loci studies of blood and brain tissue samples. We found that 152 probes corresponding to 113 genes were epigenetically associated with AD at a Bonferroni-adjusted significance level of 5.49E-07. Of these, 10 genes had significant probes in both brain-specific and blood-based analyses. Comparing males vs. females and hypertensive vs. non-hypertensive subjects, we found that 22 and 79 probes had group-specific associations with AD, respectively, suggesting a potential role for such epigenetic modifications in the heterogeneous nature of AD. Our analyses provided stronger evidence for possible roles of four genes (i.e., AIM2, C16orf80, DGUOK, and ST14) in AD pathogenesis as they were also transcriptionally associated with AD. The identified associations suggest a list of prioritized genes for follow-up functional studies and advance our understanding of AD pathogenesis.
Use of Saliva for Diagnosis and Monitoring the SARS-CoV-2: A General Perspective
Authors: Ceron Jose , Lamy Elsa , Martinez-Subiela Silvia , Lopez-Jornet Pia , Capela-Silva Fernando , Eckersall Peter , Tvarijonaviciute Asta
Published: May 2020

In this report, updated information and future perspectives about the use of saliva as a sample for laboratory analysis of the Covid-19 are highlighted. Saliva can be used for the direct detection of the SARS-CoV-2 virus, the quantification of the specific immunoglobulins produced against it, and for the evaluation of the non-specific, innate immune response of the patient. Moreover, a deeper knowledge of potential changes in the saliva proteome in this disease may allow the identification of new diagnostic and prognostic biomarkers, or even help our understanding of the mechanisms associated with the disease. With the development of appropriate sample collection and processing methods and the use of adequate assays, saliva can provide useful clinical information about the disease and could be potentially included in guidelines for sample collection for the diagnosis, disease management, and control of Covid-19.
Population-Based Screening or Targeted Screening Based on Initial Clinical Risk Assessment for Atrial Fibrillation: A Report from the Huawei Heart Study
Authors: Guo Yutao , Wang Hao , Zhang Hui , Chen Yundai , Lip Gregory Y. H.
Published: May 2020

Background: A general-population approach has been advocated to improve the screening of patients with atrial fibrillation (AF). A more pragmatic alternative may be targeted screening of patients at high risk of developing AF. We assess the value of a simple clinical risk score, C2HEST (C2, coronary artery disease/chronic obstructive pulmonary disease; COPD (1 point each); H, hypertension; E, elderly (age ≥75, doubled); S, systolic heart failure; HF (doubled); T, hyperthyroidism)); to facilitate population screening and detection of incident AF in the general population, in a prespecified ancillary analysis of the Huawei Heart Study. Methods: The Huawei Heart Study investigated general population screening for AF, identified using photoplethysmography (PPG)-based HUAWEI smart devices. We compared the value of a general population approach to a target screening approach between 26 October 2018 and 20 November 2019. Results: There were 644,124 individuals (mean age ± standard deviation, SD 34 ± 11; female 15.9%) who monitored their pulse rhythm using smart devices, among which 209,274 individuals (mean age 34 years, SD11; 10.6% female) completed the questionnaire on cardiovascular risk factors, with 739 detecting AF. Of these, 31.4% (n = 65,810) subjects reported palpitations. The median (interquartile range, IQR) duration to first detected AF was 11 (1–46), 6 (1–49), and 4 (1–24) in the population with low, intermediate, and high C2HEST score category, respectively (p = 0.03). Detected AF events rates increased with increasing C2HEST score points, stratified by age (p for trend, p < 0.001). Hazard ratios of the components of the C2HEST score for detected AF were between 1.31 and 2.75. A combination of symptomatic palpitations and C2HEST score increased prediction of AF detection, compared to using C2HEST score alone (c-indexes 0.72 vs. 0.76, Delong test, p < 0.001). Conclusions: The C2HEST score, especially when combined with symptoms, could facilitate a targeted population-based screening and preventive strategy for AF.
Update for Anaesthetists on Clinical Features of COVID-19 Patients and Relevant Management
Authors: Preckel Benedikt , Schultz Marcus J. , Vlaar Alexander P. , Hulst Abraham H. , Hermanides Jeroen , de Jong Menno D. , Schlack Wolfgang S. , Stevens Markus F. , Weenink Robert P. , Hollmann Markus W.
Published: May 2020

When preparing for the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the coronavirus infection disease (COVID-19) questions arose regarding various aspects concerning the anaesthetist. When reviewing the literature it became obvious that keeping up-to-date with all relevant publications is almost impossible. We searched for and summarised clinically relevant topics that could help making clinical decisions. This is a subjective analysis of literature concerning specific topics raised in our daily practice (e.g., clinical features of COVID-19 patients; ventilation of the critically ill COVID-19 patient; diagnostic of infection with SARS-CoV-2; stability of the virus; Covid-19 in specific patient populations, e.g., paediatrics, immunosuppressed patients, patients with hypertension, diabetes mellitus, kidney or liver disease; co-medication with non-steroidal anti-inflammatory drugs (NSAIDs); antiviral treatment) and we believe that these answers help colleagues in clinical decision-making. With ongoing treatment of severely ill COVID-19 patients other questions will come up. While respective guidelines on these topics will serve clinicians in clinical practice, regularly updating all guidelines concerning COVID-19 will be a necessary, although challenging task in the upcoming weeks and months. All recommendations during the current extremely rapid development of knowledge must be evaluated on a daily basis, as suggestions made today may be out-dated with the new evidence available tomorrow.
Current and Desired Quality of Life in People with Parkinson’s Disease: The Calman Gap Increases with Depression
Authors: Prell Tino , Teschner Ulrike , Witte Otto W. , Kunze Albrecht
Published: May 2020

Hopes and expectations often differ from current experiences. This so-called Calman gap influences quality of life (QoL). We investigated this gap in 77 elderly patients with Parkinson’s disease (PD), 25 patients with epilepsy, and 39 age-matched healthy older adults using a novel QoL questionnaire, where current and desired states were marked on a visual analogue scale. We studied the relationships between (1) epidemiological factors, (2) current and desired QoL, as well as the difference between the latter two. Current QoL was determined by depression, education level, living situation, and condition (PD, epilepsy, control). In contrast, desired QoL was essentially determined by the presence of a disease (condition), education level, and age, but not by depression. In particular, the presence of PD, lower education level, and higher age was correlated with lower expectations. In patients with PD, the gap between the current and desired QoL was largest for pain and physical functions. Accordingly, the significant effects of depression were observed only for mean current QoL, but not for desired QoL. Therefore, depression mainly influences current but not desired QoL in patients with PD. Depressed patients with PD had significantly worse QoL than PD patients without depression, although they both had almost the same desired QoL and hence, depressed PD patients had a larger Calman gap between current and desired QoL.