bluuebunny/crossref_metadata_2025 huggingface dataset:
A CMOS Active Rectifier with Time Domain Technique to Enhance PCE
Authors: Kao Shao-Ku
Published: June 2021

This paper presents a CMOS active rectifier with a time-domain technique to enhance power efficiency. A delay compensation circuit was designed using a time-domain technique. It converts the delay buffer’s delay time to a voltage value. The voltage is able to control on/off time in the comparator for variable input voltage. This circuit is designed in 0.18 m CMOS process. The input voltage range is from 2 V to 3.8 V with the output voltage from 1.8 V to 3.6 V. The efficiency can be maintained at more than 83% when the load is from 100 Ω to 1300 Ω for 3.3 V input voltage. The maximum efficiency is 90.3% at output power to be 109 mW for 3.3 V input voltage.
Optimal Placement and Sizing of D-STATCOM in Radial and Meshed Distribution Networks Using a Discrete-Continuous Version of the Genetic Algorithm
Authors: Castiblanco-Pérez Cristian Mateo , Toro-Rodríguez David Esteban , Montoya Oscar Danilo , Giral-Ramírez Diego Armando
Published: June 2021

In this paper, we propose a new discrete-continuous codification of the Chu–Beasley genetic algorithm to address the optimal placement and sizing problem of the distribution static compensators (D-STATCOM) in electrical distribution grids. The discrete part of the codification determines the nodes where D-STATCOM will be installed. The continuous part of the codification regulates their sizes. The objective function considered in this study is the minimization of the annual operative costs regarding energy losses and installation investments in D-STATCOM. This objective function is subject to the classical power balance constraints and devices’ capabilities. The proposed discrete-continuous version of the genetic algorithm solves the mixed-integer non-linear programming model that the classical power balance generates. Numerical validations in the 33 test feeder with radial and meshed configurations show that the proposed approach effectively minimizes the annual operating costs of the grid. In addition, the GAMS software compares the results of the proposed optimization method, which allows demonstrating its efficiency and robustness.
Electrical Load Prediction Using Interval Type-2 Atanassov Intuitionist Fuzzy System: Gravitational Search Algorithm Tuning Approach
Authors: Khanesar Mojtaba Ahmadieh , Lu Jingyi , Smith Thomas , Branson David
Published: June 2021

Establishing accurate electrical load prediction is vital for pricing and power system management. However, the unpredictable behavior of private and industrial users results in uncertainty in these power systems. Furthermore, the utilization of renewable energy sources, which are often variable in their production rates, also increases the complexity making predictions even more difficult. In this paper an interval type-2 intuitionist fuzzy logic system whose parameters are trained in a hybrid fashion using gravitational search algorithms with the ridge least square algorithm is presented for short-term prediction of electrical loading. Simulation results are provided to compare the performance of the proposed approach with that of state-of-the-art electrical load prediction algorithms for Poland, and five regions of Australia. The simulation results demonstrate the superior performance of the proposed approach over seven different current state-of-the-art prediction algorithms in the literature, namely: SVR, ANN, ELM, EEMD-ELM-GOA, EEMD-ELM-DA, EEMD-ELM-PSO and EEMD-ELM-GWO.
Central Tunicate Swarm NFOPID-Based Load Frequency Control of the Egyptian Power System Considering New Uncontrolled Wind and Photovoltaic Farms
Authors: Fayek Hady H. , Kotsampopoulos Panos
Published: June 2021

This paper presents load frequency control of the 2021 Egyptian power system, which consists of multi-source electrical power generation, namely, a gas and steam combined cycle, and hydro, wind and photovoltaic power stations. The simulation model includes five generating units considering physical constraints such as generation rate constraints (GRC) and the speed governor dead band. It is assumed that a centralized controller is located at the national control center to regulate the frequency of the grid. Four controllers are applied in this research: PID, fractional-order PID (FOPID), non-linear PID (NPID) and non-linear fractional-order PID (NFOPID), to control the system frequency. The design of each controller is conducted based on the novel tunicate swarm algorithm at each operating condition. The novel method is compared to other widely used optimization techniques. The results show that the tunicate swarm NFOPID controller leads the Egyptian power system to a better performance than the other control schemes. This research also presents a comparison between four methods to self-tune the NFOPID controller at each operating condition.
The Importance of Optical Fibres for Internal Temperature Sensing in Lithium-ion Batteries during Operation
Authors: Wahl Markus S. , Spitthoff Lena , Muri Harald I. , Jinasena Asanthi , Burheim Odne S. , Lamb Jacob J.
Published: June 2021

Lithium-ion batteries (LiBs) are widely used as energy storage systems (ESSs). The biggest challenge they face is retaining intrinsic health under all conditions, and understanding internal thermal behaviour is crucial to this. The key concern is the potentially large temperature differences at high charge/discharge rates. Excess heat created during charge/discharge will accelerate irreversible aging, eventually leading to failure. As a consequence, it is important to keep battery states within their safe operating range, which is determined by voltage, temperature, and current windows. Due to the chemically aggressive and electrically noisy environment, internal temperature measurement is difficult. As a result, non-invasive sensors must be physically stable, electromagnetic interference-resistant, and chemically inert. These characteristics are provided by fibre Bragg grating (FBG) sensors, which are also multiplexable. This review article discusses the thermal problems that arise during LiB use, as well as their significance in terms of LiB durability and protection. FBG-based sensors are described as a technology, with emphasis on their importance for direct temperature measurement within the LiB cell.
Variable Energy Fluxes and Exact Relations in Magnetohydrodynamics Turbulence
Authors: Verma Mahendra , Sharma Manohar , Chatterjee Soumyadeep , Alam Shadab
Published: June 2021

In magnetohydrodynamics (MHD), there is a transfer of energy from the velocity field to the magnetic field in the inertial range itself. As a result, the inertial-range energy fluxes of velocity and magnetic fields exhibit significant variations. Still, these variable energy fluxes satisfy several exact relations due to conservation of energy. In this paper, using numerical simulations, we quantify the variable energy fluxes of MHD turbulence, as well as verify several exact relations. We also study the energy fluxes of Elsässer variables that are constant in the inertial range.
A Novel Method for Food Market Regulation by Emotional Tendencies Predictions from Food Reviews Based on Blockchain and SAEs
Authors: Hao Zhihao , Wang Guancheng , Mao Dianhui , Zhang Bob , Li Haisheng , Zuo Min , Zhao Zhihua , Yen Jerome
Published: June 2021

As a part of food safety research, researches on food transactions safety has attracted increasing attention recently. Food choice is an important factor affecting food transactions safety: It can reflect consumer preferences and provide a basis for market regulation. Therefore, this paper proposes a food market regulation method based on blockchain and a deep learning model: Stacked autoencoders (SAEs). Blockchain is used to ensure the fairness of transactions and achieve transparency within the transaction process, thereby reducing the complexity of the trading environment. In order to enhance the usability, relevant Web pages have been developed to make it more friendly and conduct a security analysis for using blockchain. Consumers’ reviews after the transactions are finished can be used to train SAEs in order to perform emotional tendencies predictions. Compared with different advanced models for predictions, the test results show that SAEs have a better performance. Furthermore, in order to provide a basis for the formulation of regulation strategies and its related policies, case studies of different traders and commodities have also been conducted, proving the effectiveness of the proposed method.
Comparing the Antimicrobial Actions of Greek Honeys from the Island of Lemnos and Manuka Honey from New Zealand against Clinically Important Bacteria
Authors: Gkoutzouvelidou Maria , Panos Georgios , Xanthou Maria Nefertiti , Papachristoforou Alexandros , Giaouris Efstathios
Published: June 2021

Honey is a natural food with a long history as a traditional medicine because of its many biological characteristics, including antimicrobial, antioxidant, anti-tumor and anti-inflammatory properties. In this study, the antimicrobial actions of eight different honeys from Lemnos island (north-eastern Greece) plus manuka honey (from New Zealand, UMF 30+, licensed in many countries as topical medical preparation) were evaluated against 10 clinically relevant bacteria, including five Gram-positive and five Gram-negative. To achieve this, an agar well diffusion assay measured the diameter of inhibition zones (mm) of two selected concentrations for each honey (25% and 12.5% v/v). The minimum inhibitory and bactericidal concentrations (MIC and MBC) of each sample were also calculated and compared against two representative bacterial species (Salmonella Typhimurium and Staphylococcus aureus) using broth microdilution and agar spot methods, respectively. The pH, water activity (aw), 5-hydroxymethylfurfural (HMF) and diastase levels, together with the pollen type and content of each honey, were also determined. Results revealed that all the Lemnos honeys presented antibacterial action, which for some samples was like that of manuka. These all had an acidic pH (3.61 ± 0.04), with a aw ≤ 0.60, while it is worth noting that those found to display the strongest antibacterial actions also presented the lowest HMF content, together with the highest diastase values, both of the latter being used as quality parameters. Pollen composition of the Lemnos honeys was multifloral, underlining the rich plant biodiversity encountered on the island. To summarize, Lemnos honeys could be further exploited as natural antimicrobial systems for use in foods and medicine.
Theanine Improves High-Dose Epigallocatechin-3-Gallate-Induced Lifespan Reduction in Caenorhabditis elegans
Authors: Peng Yuxuan , Dai Shen , Lu Yan , Xiong Ligui , Huang Jianan , Liu Zhonghua , Gong Yushun
Published: June 2021

Epigallocatechin-3-gallate (EGCG) is the most abundant polyphenol in green tea. Our previous report showed that induced hormesis was a critical determinant for the promotion of a healthy lifespan in Caenorhabditis elegans. In the present study, we investigated the anti-aging effects of the main active ingredients in green tea. We found that galloylated catechins (EGCG and epicatechin gallate) could extend the lifespan of C. elegans, while their metabolites (gallic acid, epicatechin, and epigallocatechin) could not. Interestingly, the combination with theanine, not caffeine, could alleviate the adverse effects induced by high-dose EGCG, including the promotion of lifespan and locomotor ability. This was due to the attenuation of the excess production of reactive oxygen species and the activation of DAF-16. These findings will facilitate further studies on the health benefits of tea active components and their interactions.
Cringe Histories: Harold Pinter and the Steptoes
Authors: Bignell Jonathan
Published: June 2021

This article argues that cringe humour in British television had begun at least by the early 1960s and derived from a theatre history in which conventions of Naturalism were modified by emergent British writers working with European avant-garde motifs. The article makes the case by analysing the importance of cringe to the BBC sitcom Steptoe and Son, tracing its form and themes back to the ‘comedy of menace’ and ‘Theatre of the Absurd’ emblematised by the early work of playwright Harold Pinter. The article links the play that made Pinter’s reputation, The Birthday Party, to dramatic tropes and social commentary identified in Steptoe and Son and in other British sitcoms with cringe elements. The analysis not only discusses relationships between the different dramatic works on stage and screen but also pursues some of the other connections between sitcom and Pinter’s drama via networks of actors and contemporaneous discourses of critical commentary. It assesses the political stakes of cringe as a comic form, particularly the failure of cringe to impel political activism, and places this in the context of the repeated broadcast of Pinter’s plays and episodes of Steptoe and Son over an extended period.
Publisher’s Note to Launch Hydrobiology
Authors: Lin Shu-Kun
Published: June 2021

When I was a student at Wuhan University, the last captive individual of baiji (Lipotes vexillifer), a species of freshwater dolphin, was living at the Freshwater Dolphin Research Centre of Wuhan Institute of Hydrobiology, Chinese Academy of Sciences [...]
Can the Human Resources Index (HRI) Be Used as a Process Feedback Measurement in a Structured Support Model for Systematic Work Environment Management?
Authors: Molin Fredrik , Paulsson Sofia Åström , Hellman Therese , Svartengren Magnus
Published: June 2021

The aim of the study was to estimate the level of the human resources index (HRI) measure among Swedish municipal employees, and to investigate the association between human resources index (HRI) and relational justice, short-term recovery, work environment-related production loss, and health-related production loss. A cross-sectional design was used with one sample of municipal employees (n = 6402). The results showed a positive association (r = 0.31) between human resources index (HRI) and relational justice; a positive (r = 0.27) association between HRI and short-term recovery; a negative association between HRI and work environment-related production loss (r = −0.37); and a negative association between HRI and health-related production loss (r = −0.23). The findings implicate that HRI captures important aspects of the work environment such as productivity, relational justice, and short-term recovery. The HRI measure is part of a support model used in workplaces to systematically address work environment-related issues. Monitoring changes in the HRI measure, it is possible to determine whether the measures taken effect production loss, perceived leadership, and short-term recovery in a work group. The support model using HRI may thus be used to complement traditional work environment surveys conducted in Swedish organizations as obliged by legal provisions.
Understanding Continuance Intention Determinants to Adopt Online Health Care Community: An Empirical Study of Food Safety
Authors: Yang Jinxin , Jong Din
Published: June 2021

The purpose of this research is to determine whether users’ social interaction tie and trust have a mediating effect on the willingness to use the online healthcare community (OHC) platform on an ongoing basis to respond to food safety crises and monitor food safety practices. During the three-month survey, we conducted an online investigation of users who had experience sharing on the OHC platform and were concerned about food safety. Thereby, three hundred and fifty-two valid questionnaires were received and partial least squares was adopted in this study to test the proposed hypotheses. The empirical results show that perceived critical mass, image, and para-social interaction strengthen the social interaction tie between users and the food safety platform. In addition, this study found that social interaction tie and trust of OHC platform users increased users’ willingness to continue using the OHC platform. This research provides OHC platform managers with an in-depth understanding of online social interactions on food safety pages. Moreover, the results of this study can help food business owners, government regulators, hospitals, and physicians to improve the way they use the Web for opinion-led food safety crises and provide insight into the intent of promoting the ongoing use of OHC platforms.
Reply to Laby, D.M.; Appelbaum, L.G. Comment on “Nascimento et al. Citations Network Analysis of Vision and Sport. Int. J. Environ. Res. Public Health 2020, 17, 7574”
Authors: Nascimento Henrique , Martinez-Perez Clara , Alvarez-Peregrina Cristina , Sánchez-Tena Miguel Ángel
Published: June 2021

In response to a comment, in this study [...]
Predictors for Depression, Sleep Disturbance, and Subjective Pain among Inpatients with Depressive Disorders during the COVID-19 Pandemic: A Cross-Sectional Study
Authors: Li Dian-Jeng , Hsu Su-Ting , Chou Frank Huang-Chih , Chou Li-Shiu , Hsieh Kuan-Ying , Kao Wei-Tsung , Lin Guei-Ging , Chen Wei-Jen , Liao Che-Hun , Huang Joh-Jong
Published: June 2021

The coronavirus disease 2019 (COVID-19) pandemic can have a negative impact on patients with mood disorders. The aim of this study is to explore the societal influence of COVID-19 and associated impacts on levels of depression, sleep disturbance, and subjective pain among patients with mood disorders. This cross-sectional study recruited inpatients with depression and bipolar disorder. Levels of depression, sleep disturbance, subjective pain, and related demographic variables were collected through self-reported questionnaires. Potential factors associated with levels of depression, sleep disturbance, and subjective pain were identified using univariate linear regression and further entered into a stepwise multivariate linear regression model to identify the independent predictors. A total of 119 participants were included in the analysis, of whom 50.42% had bipolar disorder and 49.58% had unipolar depression. Multivariate analysis showed that a higher level of depression was associated with female subjects, subjects with partners, present history of psychological trauma, and drinking alcohol. Sleep disturbance was associated with subjects with partners and drinking alcohol. A higher level of subjective pain was associated with a higher level of social anxiety and a history of psychological trauma. The current study identified several predictors of psychological burden and subjective pain among inpatients with depression during the COVID-19 pandemic. Further investigations are warranted to extend the application and generalizability of our results.
The Characteristics of Patients with Oral Lichen Planus and Malignant Transformation—A Retrospective Study of 271 Patients
Authors: Radochová Vladimíra , Koberová Ivančaková Romana , Heneberk Ondřej , Slezák Radovan
Published: June 2021

Introduction: Oral lichen planus (OLP) is a chronic inflammatory disease with an unknown etiology rating among oral potentially malignant disorder. The aim of the study was to determine the epidemiological and clinical characteristics of the patients with OLP and rate of malignant transformation. Patients and methods: Data were obtained from the medical records of 271 patients referred to the Oral Medicine Unit at the University Hospital in Hradec Králové diagnosed with oral lichen planus in the period of 2003–2020. The records were retrospectively analyzed. The following clinical data were retrieved from the medical charts: gender, age, systemic diseases, alcohol and tobacco consumption, localization/clinical appearance of lesions, distribution of the lesions, presence of the symptoms, treatment provided and malignant transformation. Results: A total of 271 charts of patients with confirmed diagnosis of OLP were retrospectively analyzed, of whom, 66.4% (180/271) were women and 33.6% (91/271) were men. The mean age of the patients was 56.0 (18.2–85.0) years. The median follow-up of all patients was 15.2 months. Overall, 2 patients (2/271, 0.74%) meeting the above-mentioned criteria for malignant transformation were identified during the follow-up period. Both patients suffered from erosive type OLP and developed squamous cell carcinoma of the tongue. Conclusions: This retrospective study is in concordance with other studies showing the similar profile and clinical features of the patients with OLP. Malignant transformation rate was 0.74%.
A Swiss Health Care Professionals’ Perspective on the Meaning of Interprofessional Collaboration in Health Care of People with MS—A Focus Group Study
Authors: Schmid Fabienne , Rogan Slavko , Glässel Andrea
Published: June 2021

Multiple sclerosis (MS) is a chronic, inflammatory autoimmune disease of the central nervous system mainly of adults ranging from 20 to 45 years of age. The risk of developing MS is 50% higher in women than in men. Most people with MS (PwMS) experience a spectrum of symptoms such as spasticity, continence dysfunctions, fatigue, or neurobehavioral manifestations. Due to the complexity of MS and the variety of patient-centered needs, a comprehensive approach of interprofessional collaboration (IPC) of multiple health care professionals (HCP) is necessary. The aim of this qualitative study was to explore the meaning of IPC in the comprehensive care of PwMS from a HCP perspective. Focus groups (FG) with HCP were conducted, recorded, and transcribed verbatim. The sample contained HCP from three MS clinics in different phases of care and rehabilitation. Four main categories emerged: (a) experience with IPC, (b) relevant aspects for IPC in patients’ treatment, (c) differences in in- and outpatient settings, and (d) influence of patient perspective. IPC plays a crucial role in HCP perspective when treating PwMS, which can benefit from an IPC therapeutic approach because HCP work together in a patient-centered way. The inpatient setting of HCP strongly supports the implementation of IPC. This prerequisite does not exist in outpatient settings.
Mental Health States Experienced by Perinatal Healthcare Workers during COVID-19 Pandemic in Italy
Authors: Cena Loredana , Rota Matteo , Calza Stefano , Massardi Barbara , Trainini Alice , Stefana Alberto
Published: June 2021

Background: The ongoing COVID-19 pandemic has had an impact on mental health status in a variety of populations. Methods: An online non-probability sample survey was used to assess psychological distress symptoms and burnout among perinatal healthcare professionals (PHPs) during the pandemic in Italy. The questionnaire included the Depression, Anxiety, and Stress Scale-21 (DASS-21) and the Maslach Burnout Inventory (MBI). Demographic and occupational factors associated with stress, anxiety, and depression symptoms were analyzed. Results: The sample size was 195. The estimated self-reported rates of moderate to severe anxiety symptoms, depression symptoms, and perceived stress levels were 18.7, 18.7, and 21.5%, respectively. Furthermore, 6.2% of respondents reported burnout. One factor associated with all three self-reported psychological distress issues was suffering from trauma unrelated to the pandemic (aOR: 7.34, 95% CI: 2.73–20.28 for depression; aOR: 6.13, 95% CI: 2.28–16.73 for anxiety; aOR: 3.20, 95% CI: 1.14–8.88 for stress). Compared to physicians, psychologists had lower odds of developing clinically significant depressive symptoms (aOR: 0.21, 95% CI: 0.04–0.94) and high stress levels (aOR: 0.19, 95% CI: 0.04–0.80). Conclusions: High rates of self-reported symptoms of depression and anxiety, as well as perceived stress, among PHPs were reported during the COVID-19 pandemic. Health authorities should implement and integrate timely and regular evidence-based assessment of psychological distress targeting PHPs in their work plans.
Early Changes in Crayfish Hemocyte Proteins after Injection with a β-1,3-glucan, Compared to Saline Injected and Naive Animals
Authors: Ekblom Charlotta , Söderhäll Kenneth , Söderhäll Irene
Published: June 2021

Early changes in hemocyte proteins in freshwater crayfish Pacifastacus leniusculus, in response to an injection with the fungal pattern recognition protein β-1,3-glucan (laminarin) were investigated, as well as changes after saline (vehicle) injection and in naïve animals. Injection of saline resulted in rapid recruitment of granular hemocytes from surrounding tissues, whereas laminarin injection on the other hand induced an initial dramatic drop of hemocytes. At six hours after injection, the hemocyte populations therefore were of different composition. The results show that mature granular hemocytes increase in number after saline injection as indicated by the high abundance of proteins present in granular cell vesicles, such as a vitelline membrane outer layer protein 1 homolog, mannose-binding lectin, masquerade, crustin 1 and serine protease homolog 1. After injection with the β-1,3-glucan, only three proteins were enhanced in expression, in comparison with saline-injected animals and uninjected controls. All of them may be associated with immune responses, such as a new and previously undescribed Kazal proteinase inhibitor. One interesting observation was that the clotting protein was increased dramatically in most of the animals injected with laminarin. The number of significantly affected proteins was very few after a laminarin injection when compared to uninjected and saline-injected crayfish. This finding may demonstrate some problematic issues with gene and protein expression studies from other crustaceans receiving injections with pathogens or pattern recognition proteins. If no uninjected controls are included and no information about hemocyte count (total or differential) is given, expressions data for proteins or mRNAs are very difficult to properly interpret.
Imidazole-Based Ionic Liquids with BF4 as the Counterion Perform Outstanding Abilities in Both Inhibiting Clay Swelling and Lowing Water Cluster Size
Authors: Zhang Qiqi , Zhang Shanmeiyu , Yang Hui , Pei Guangling , Yang Ming , Zhang Wei , Chen Rui , Wang Jinben
Published: June 2021

Promoting fluid transportation in porous media has important applications in energy, pedology, bioscience, etc. For this purpose, one effective way is to prevent swelling through surface modification; however, it is far from enough in real cases, such as ultra-low permeability reservoirs and tight oils. In this study, we considered the comprehensive effects of inhibiting clay swelling, flocculation performance, reducing water clusters and interfacial tension and developed a series of imidazole-based tetrafluoroborate ionic liquids (ILs) with different lengths of alkyl chains. Through measurements of anti-swelling rates, XRD, SEM, 17O NMR, molecular dynamics simulation, zeta potential, flocculation evaluation, interfacial tension and a core flooding experiment based on ultra-low permeability reservoirs, the relationships between the molecular structure and physicochemical properties of ILs have been revealed. Interestingly, one of the selected ILs, imidazole-based tetrafluoroborate ILs (C8-OMImBF4), shows excellent performance, which is helpful to design an effective strategy in promoting fluid transportation in narrow spaces.
Molecular and Functional Analysis of Sunitinib-Resistance Induction in Human Renal Cell Carcinoma Cells
Authors: Rausch Magdalena , Rutz Adriano , Allard Pierre-Marie , Delucinge-Vivier Céline , Docquier Mylène , Dormond Olivier , Wolfender Jean-Luc , Nowak-Sliwinska Patrycja
Published: June 2021

Resistance in clear cell renal cell carcinoma (ccRCC) against sunitinib is a multifaceted process encompassing numerous molecular aberrations. This induces clinical complications, reducing the treatment success. Understanding these aberrations helps us to select an adapted treatment strategy that surpasses resistance mechanisms, reverting the treatment insensitivity. In this regard, we investigated the dominant mechanisms of resistance to sunitinib and validated an optimized multidrug combination to overcome this resistance. Human ccRCC cells were exposed to single or chronic treatment with sunitinib to obtain three resistant clones. Upon manifestation of sunitinib resistance, morphometric changes in the cells were observed. At the molecular level, the production of cell membrane and extracellular matrix components, chemotaxis, and cell cycle progression were dysregulated. Molecules enforcing the cell cycle progression, i.e., cyclin A, B1, and E, were upregulated. Mass spectrometry analysis revealed the intra- and extracellular presence of N-desethyl sunitinib, the active metabolite. Lysosomal sequestration of sunitinib was confirmed. After treatment with a synergistic optimized drug combination, the cell metabolic activity in Caki-1-sunitinib-resistant cells and 3D heterotypic co-cultures was reduced by >80%, remaining inactive in non-cancerous cells. These results demonstrate geno- and phenotypic changes in response to sunitinib treatment upon resistance induction. Mimicking resistance in the laboratory served as a platform to study drug responses.
The Muscle-Brain Axis and Neurodegenerative Diseases: The Key Role of Mitochondria in Exercise-Induced Neuroprotection
Authors: Burtscher Johannes , Millet Grégoire P. , Place Nicolas , Kayser Bengt , Zanou Nadège
Published: June 2021

Regular exercise is associated with pronounced health benefits. The molecular processes involved in physiological adaptations to exercise are best understood in skeletal muscle. Enhanced mitochondrial functions in muscle are central to exercise-induced adaptations. However, regular exercise also benefits the brain and is a major protective factor against neurodegenerative diseases, such as the most common age-related form of dementia, Alzheimer’s disease, or the most common neurodegenerative motor disorder, Parkinson’s disease. While there is evidence that exercise induces signalling from skeletal muscle to the brain, the mechanistic understanding of the crosstalk along the muscle–brain axis is incompletely understood. Mitochondria in both organs, however, seem to be central players. Here, we provide an overview on the central role of mitochondria in exercise-induced communication routes from muscle to the brain. These routes include circulating factors, such as myokines, the release of which often depends on mitochondria, and possibly direct mitochondrial transfer. On this basis, we examine the reported effects of different modes of exercise on mitochondrial features and highlight their expected benefits with regard to neurodegeneration prevention or mitigation. In addition, knowledge gaps in our current understanding related to the muscle–brain axis in neurodegenerative diseases are outlined.
Severe Adverse Drug Reactions to Quetiapine in Two Patients Carrying CYP2D6*4 Variants: A Case Report
Authors: Stäuble Céline K. , Lampert Markus L. , Mikoteit Thorsten , Hatzinger Martin , Hersberger Kurt E. , Meyer zu Schwabedissen Henriette E.
Published: June 2021

We report two cases of patients who developed severe adverse drug reactions including persistent movement disorders, nausea, and vertigo during treatment with quetiapine at maximum daily doses ranging between 300 and 400 mg. The extensive hepatic metabolism of quetiapine is mainly attributed to cytochrome P450 3A4 (CYP3A4). However, there is recent evidence supporting the idea of CYP2D6 playing a role in the clearance of the quetiapine active metabolite norquetiapine. Interestingly, both patients we are reporting of are carriers of the CYP2D6*4 variant, predicting an intermediate metabolizer phenotype. Additionally, co-medication with a known CYP2D6 inhibitor and renal impairment might have further affected quetiapine pharmacokinetics. The herein reported cases could spark a discussion on the potential impact of a patient’s pharmacogenetic predisposition in the treatment with quetiapine. However, further studies are warranted to promote the adoption of pharmacogenetic testing for the prevention of drug-induced toxicities associated with quetiapine.
The Role of Calcium in Wound Healing
Authors: Subramaniam Thayaalini , Fauzi Mh Busra , Lokanathan Yogeswaran , Law Jia Xian
Published: June 2021

Skin injury is quite common, and the wound healing is a complex process involving many types of cells, the extracellular matrix, and soluble mediators. Cell differentiation, migration, and proliferation are essential in restoring the integrity of the injured tissue. Despite the advances in science and technology, we have yet to find the ideal dressing that can support the healing of cutaneous wounds effectively, particularly for difficult-to-heal chronic wounds such as diabetic foot ulcers, bed sores, and venous ulcers. Hence, there is a need to identify and incorporate new ideas and methods to design a more effective dressing that not only can expedite wound healing but also can reduce scarring. Calcium has been identified to influence the wound healing process. This review explores the functions and roles of calcium in skin regeneration and reconstruction during would healing. Furthermore, this review also investigates the possibility of incorporating calcium into scaffolds and examines how it modulates cutaneous wound healing. In summary, the preliminary findings are promising. However, some challenges remain to be addressed before calcium can be used for cutaneous wound healing in clinical settings.
2-O-Methylhonokiol Suppresses HCV Replication via TRAF6-Mediated NF-kB Activation
Authors: Jeong Suyun , Lee Young-seok , Kim Kiyoon , Yoon Ji-su , Kim Sungsoo , Ha Joohun , Kang Insug , Choe Wonchae
Published: June 2021

Hepatitis C virus (HCV) is associated with various liver diseases. Chronic HCV infection is characterized by an abnormal host immune response. Therefore, it is speculated that to suppress HCV, a well-regulated host immune response is necessary. 2-O-methylhonokiol was identified by the screening of anti-HCV compounds using Renilla luciferase assay in Huh 7.5/Con 1 genotype 1b replicon cells. Here, we investigated the mechanism by which 2-O-methylhonokiol treatment inhibits HCV replication using real-time PCR. Our data shows that treatment with 2-O-methylhonokiol activated innate immune responses via nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) pathway. Additionally, the immunoprecipitation result shows that treatment with 2-O-methylhonokiol augmented tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6) by preventing p62 from binding to TRAF6, resulting in reduced autophagy caused by HCV. Finally, we reproduced our data with the conditioned media from 2-O-methylhonokiol-treated cells. These findings strongly suggest that 2-O-methylhonokiol enhances the host immune response and suppresses HCV replication via TRAF6-mediated NF-kB activation.
18F-Sodium Fluoride PET as a Diagnostic Modality for Metabolic, Autoimmune, and Osteogenic Bone Disorders: Cellular Mechanisms and Clinical Applications
Authors: Park Peter Sang Uk , Raynor William Y. , Sun Yusha , Werner Thomas J. , Rajapakse Chamith S. , Alavi Abass
Published: June 2021

In a healthy body, homeostatic actions of osteoclasts and osteoblasts maintain the integrity of the skeletal system. When cellular activities of osteoclasts and osteoblasts become abnormal, pathological bone conditions, such as osteoporosis, can occur. Traditional imaging modalities, such as radiographs, are insensitive to the early cellular changes that precede gross pathological findings, often leading to delayed disease diagnoses and suboptimal therapeutic strategies. 18F-sodium fluoride (18F-NaF)-positron emission tomography (PET) is an emerging imaging modality with the potential for early diagnosis and monitoring of bone diseases through the detection of subtle metabolic changes. Specifically, the dissociated 18F- is incorporated into hydroxyapatite, and its uptake reflects osteoblastic activity and bone perfusion, allowing for the quantification of bone turnover. While 18F-NaF-PET has traditionally been used to detect metastatic bone disease, recent literature corroborates the use of 18F-NaF-PET in benign osseous conditions as well. In this review, we discuss the cellular mechanisms of 18F-NaF-PET and examine recent findings on its clinical application in diverse metabolic, autoimmune, and osteogenic bone disorders.
Engineering of a Biomimetic Interface between a Native Dental Tissue and Restorative Composite and Its Study Using Synchrotron FTIR Microscopic Mapping
Authors: Seredin Pavel , Goloshchapov Dmitry , Ippolitov Yuri , Vongsvivut Jitraporn
Published: June 2021

The aim of this work is to develop a biomimetic interface between the natural tooth tissue and the restorative composite and to study it on the basis of synchrotron micro-FTIR mapping and multidimensional processing of the spectral data array. Using hierarchical cluster analysis of 3D FTIR data revealed marked improvements in the formation of the dentine/adhesive/dental hybrid interface using a biomimetic approach. The use of a biomimetic strategy (application of an amino acid–modified primer, alkaline calcium and a nano-c-HAp–modified adhesive) allowed the formation of a matrix that can be structurally integrated with natural dentine and dental composite. The biomimetic hybrid layer was characterised by homogeneous chemical composition and a higher degree of conversion of the adhesive during polymerisation, which should provide optimal integration of the dental composite with the dentine.
Functional Characterization of Two Novel Mutations in SCN5A Associated with Brugada Syndrome Identified in Italian Patients
Authors: Balla Cristina , Conte Elena , Selvatici Rita , Marsano Renè Massimiliano , Gerbino Andrea , Farnè Marianna , Blunck Rikard , Vitali Francesco , Armaroli Annarita , Brieda Alessandro , Liantonio Antonella , De Luca Annamaria , Ferlini Alessandra , Rapezzi Claudio , Bertini Matteo , Gualandi Francesca , Imbrici Paola
Published: June 2021

Background. Brugada syndrome (BrS) is an autosomal dominantly inherited cardiac disease characterized by “coved type” ST-segment elevation in the right precordial leads, high susceptibility to ventricular arrhythmia and a family history of sudden cardiac death. The SCN5A gene, encoding for the cardiac voltage-gated sodium channel Nav1.5, accounts for ~20–30% of BrS cases and is considered clinically relevant. Methods. Here, we describe the clinical findings of two Italian families affected by BrS and provide the functional characterization of two novel SCN5A mutations, the missense variant Pro1310Leu and the in-frame insertion Gly1687_Ile1688insGlyArg. Results. Despite being clinically different, both patients have a family history of sudden cardiac death and had history of arrhythmic events. The Pro1310Leu mutation significantly reduced peak sodium current density without affecting channel membrane localization. Changes in the gating properties of expressed Pro1310Leu channel likely account for the loss-of-function phenotype. On the other hand, Gly1687_Ile1688insGlyArg channel, identified in a female patient, yielded a nearly undetectable sodium current. Following mexiletine incubation, the Gly1687_Ile1688insGlyArg channel showed detectable, albeit very small, currents and biophysical properties similar to those of the Nav1.5 wild-type channel. Conclusions. Overall, our results suggest that the degree of loss-of-function shown by the two Nav1.5 mutant channels correlates with the aggressive clinical phenotype of the two probands. This genotype-phenotype correlation is fundamental to set out appropriate therapeutical intervention.
Inhibition of Carotenoid Biosynthesis by CRISPR/Cas9 Triggers Cell Wall Remodelling in Carrot
Authors: Oleszkiewicz Tomasz , Klimek-Chodacka Magdalena , Kruczek Michał , Godel-Jędrychowska Kamila , Sala Katarzyna , Milewska-Hendel Anna , Zubko Maciej , Kurczyńska Ewa , Qi Yiping , Baranski Rafal
Published: June 2021

Recent data indicate that modifications to carotenoid biosynthesis pathway in plants alter the expression of genes affecting chemical composition of the cell wall. Phytoene synthase (PSY) is a rate limiting factor of carotenoid biosynthesis and it may exhibit species-specific and organ-specific roles determined by the presence of psy paralogous genes, the importance of which often remains unrevealed. Thus, the aim of this work was to elaborate the roles of two psy paralogs in a model system and to reveal biochemical changes in the cell wall of psy knockout mutants. For this purpose, Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR associated (Cas9) proteins (CRISPR/Cas9) vectors were introduced to carotenoid-rich carrot (Daucus carota) callus cells in order to induce mutations in the psy1 and psy2 genes. Gene sequencing, expression analysis, and carotenoid content analysis revealed that the psy2 gene is critical for carotenoid biosynthesis in this model and its knockout blocks carotenogenesis. The psy2 knockout also decreased the expression of the psy1 paralog. Immunohistochemical staining of the psy2 mutant cells showed altered composition of arabinogalactan proteins, pectins, and extensins in the mutant cell walls. In particular, low-methylesterified pectins were abundantly present in the cell walls of carotenoid-rich callus in contrast to the carotenoid-free psy2 mutant. Transmission electron microscopy revealed altered plastid transition to amyloplasts instead of chromoplasts. The results demonstrate for the first time that the inhibited biosynthesis of carotenoids triggers the cell wall remodelling.
Binding Properties of a Dinuclear Zinc(II) Salen-Type Molecular Tweezer with a Flexible Spacer in the Formation of Lewis Acid-Base Adducts with Diamines
Authors: Munzi Gabriella , Consiglio Giuseppe , Failla Salvatore , Di Bella Santo
Published: June 2021

In this paper we report the binding properties, by combined 1H NMR, optical absorption, and fluorescence studies, of a molecular tweezer composed of two Zn(salen)-type Schiff-base units connected by a flexible spacer, towards a series of ditopic diamines having a strong Lewis basicity, with different chain length and rigidity. Except for the 1,2-diaminoethane, in all other cases the formation of stable 1:1 Lewis acid-base adducts with large binding constants is demonstrated. For α,ω-aliphatic diamines, binding constants progressively increase with the increasing length of the alkyl chain, thanks to the flexible nature of the spacer and the parallel decreased conformational strain upon binding. Stable adducts are also found even for short diamines with rigid molecular structures. Given their preorganized structure, these latter species are not subjected to loss of degrees of freedom. The binding characteristics of the tweezer have been exploited for the colorimetric and fluorometric selective and sensitive detection of piperazine.
Medical Device Regulation Efforts for mHealth Apps during the COVID-19 Pandemic—An Experience Report of Corona Check and Corona Health
Authors: Holfelder Marc , Mulansky Lena , Schlee Winfried , Baumeister Harald , Schobel Johannes , Greger Helmut , Hoff Andreas , Pryss Rüdiger
Published: June 2021

Within the healthcare environment, mobile health (mHealth) applications (apps) are becoming more and more important. The number of new mHealth apps has risen steadily in the last years. Especially the COVID-19 pandemic has led to an enormous amount of app releases. In most countries, mHealth applications have to be compliant with several regulatory aspects to be declared a “medical app”. However, the latest applicable medical device regulation (MDR) does not provide more details on the requirements for mHealth applications. When developing a medical app, it is essential that all contributors in an interdisciplinary team—especially software engineers—are aware of the specific regulatory requirements beforehand. The development process, however, should not be stalled due to integration of the MDR. Therefore, a developing framework that includes these aspects is required to facilitate a reliable and quick development process. The paper at hand introduces the creation of such a framework on the basis of the Corona Health and Corona Check apps. The relevant regulatory guidelines are listed and summarized as a guidance for medical app developments during the pandemic and beyond. In particular, the important stages and challenges faced that emerged during the entire development process are highlighted.
Differentiation of Idiopathic Pulmonary Fibrosis from Connective Tissue Disease-Related Interstitial Lung Disease Using Quantitative Imaging
Authors: Chung Jonathan H. , Adegunsoye Ayodeji , Cannon Brenna , Vij Rekha , Oldham Justin M. , King Christopher , Montner Steven M. , Thirkateh Prahasit , Barnett Scott , Karwoski Ronald , Bartholmai Brian J. , Strek Mary , Nathan Steven D.
Published: June 2021

A usual interstitial pneumonia (UIP) imaging pattern can be seen in both idiopathic pulmonary fibrosis (IPF) and connective tissue disease-related interstitial lung disease (CTD-ILD). The purpose of this multicenter study was to assess whether quantitative imaging data differ between IPF and CTD-ILD in the setting of UIP. Patients evaluated at two medical centers with CTD-ILD or IPF and a UIP pattern on CT or pathology served as derivation and validation cohorts. Chest CT data were quantitatively analyzed including total volumes of honeycombing, reticulation, ground-glass opacity, normal lung, and vessel related structures (VRS). VRS was compared with forced vital capacity percent predicted (FVC%) and percent predicted diffusing capacity of the lungs for carbon monoxide (DLCO%). There were 296 subjects in total, with 40 CTD-ILD and 85 IPF subjects in the derivation cohort, and 62 CTD-ILD and 109 IPF subjects in the validation cohort. VRS was greater in IPF across the cohorts on univariate (p < 0.001) and multivariable (p < 0.001–0.047) analyses. VRS was inversely correlated with DLCO% in both cohorts on univariate (p < 0.001) and in the derivation cohort on multivariable analysis (p = 0.003) but not FVC%. Total volume of normal lung was associated with DLCO% (p < 0.001) and FVC% (p < 0.001–0.009) on multivariable analysis in both cohorts. VRS appears to have promise in differentiating CTD-ILD from IPF. The underlying pathophysiological relationship between VRS and ILD is complex and is likely not explained solely by lung fibrosis.
Neutrophil to Lymphocyte Ratio in Maternal Blood: A Clue to Suspect Amnionitis
Authors: Lee Joon-Hyung , Park Chan-Wook , Moon Kyung-Chul , Park Joong-Shin , Jun Jong-Kwan
Published: June 2021

There is no information about whether maternal neutrophil to lymphocyte ratios (NLRs) progressively increase with respect to the progression of acute histologic chorioamnionitis (acute-HCA) and increased maternal NLR is a risk factor for amnionitis, known as advanced acute-HCA, in pregnant women at risk for spontaneous preterm birth (PTB). The objective of the current study is to examine this issue. The study population included 132 singleton PTB (<34 weeks) due to either preterm labor or preterm-PROM with both placental pathology and maternal CBC results within 48 h before delivery. We examined maternal NLRs according to the progression of acute-HCA in extra-placental membranes (EPM) (i.e., group-0, inflammation-free EPM; group-1, inflammation restricted to decidua; group-2, inflammation restricted to the membranous trophoblast of chorion and the decidua; group-3, inflammation in the connective tissue of chorion but not amnion; group-4, amnionitis). Maternal NLRs significantly and progressively increased with the progression of acute-HCA (Spearman’s rank correlation test, γ = 0.363, p = 0.000019). Moreover, the increased maternal NLR (≥7.75) (Odds-ratio 5.56, 95% confidence-interval 1.26-24.62, p < 0.05) was a significant independent risk factor for amnionitis even after the correction for potential confounders. In conclusion, maternal NLRs significantly and progressively increased according to the progression of acute-HCA and the increased maternal NLR (≥7.75) was an independent risk factor for amnionitis in spontaneous PTB. The evaluation of the performance of NLR should clearly require a prospective description of this parameter in a cohort of patients with either threatened PTL or preterm-PROM.