bluuebunny/crossref_metadata_2025 huggingface dataset:
Life Expectancy of the Ethnically Mixed: Register-Based Evidence from Native Finns
Authors: Reini Kaarina , Saarela Jan
Published: March 2021

As the ethnic composition around the world is becoming more diverse, the need to produce vital statistics for ethnically mixed populations is continuously increasing. Our aim is to provide the first life expectancy estimates for individuals with uniform Finnish, uniform Swedish, and mixed Finnish-Swedish backgrounds, based on individuals in the native population of Finland who can be linked to both their parents. Life expectancy at birth in the period 2005–2015 was calculated from population and mortality numbers at the one-year level based on each person’s sex, year of birth, and the unique ethnolinguistic affiliation of the index person and each parent. Swedish-registered individuals with Swedish-registered parents had the longest life expectancy at birth, or 85.68 years (95% CI: 85.60–85.77) for females and 81.36 for males (95% CI: 81.30–81.42), as compared to 84.76 years (95% CI: 84.72–84.79) and 78.89 years (95% CI: 78.86–78.92) for Finnish-registered females and males with Finnish-registered parents. Persons with mixed backgrounds were found in between those with uniform Finnish and uniform Swedish backgrounds. An individual’s own ethnolinguistic affiliation is nevertheless more important for longevity than parental affiliation. Similar register-based analyses for other countries with mixed populations would be useful.
The Integration of Psychosocial Care into National Dementia Strategies across Europe: Evidence from the Skills in DEmentia Care (SiDECar) Project
Authors: Chirico Ilaria , Chattat Rabih , Dostálová Vladimíra , Povolná Pavla , Holmerová Iva , de Vugt Marjolein E. , Janssen Niels , Dassen Fania , Sánchez-Gómez María Cruz , García-Peñalvo Francisco José , Franco-Martín Manuel A. , Ottoboni Giovanni
Published: March 2021

There is evidence supporting the use of psychosocial interventions in dementia care. Due to the role of policy in clinical practice, the present study investigates whether and how the issue of psychosocial care and interventions has been addressed in the national dementia plans and strategies across Europe. A total of 26 national documents were found. They were analyzed by content analysis to identify the main pillars associated with the topic of psychosocial care and interventions. Specifically, three categories emerged: (1) Treatment, (2) Education, and (3) Research. The first one was further divided into three subcategories: (1) Person-centred conceptual framework, (2) Psychosocial interventions, and (3) Health and social services networks. Overall, the topic of psychosocial care and interventions has been addressed in all the country policies. However, the amount of information provided differs across the documents, with only the category of ‘Treatment’ covering all of them. Furthermore, on the basis of the existing policies, how the provision of psychosocial care and interventions would be enabled, and how it would be assessed are not fully apparent yet. Findings highlight the importance of policies based on a comprehensive and well-integrated system of care, where the issue of psychosocial care and interventions is fully embedded.
Analysis of Inadequacies in Hospital Care through Medical Liability Litigation
Authors: La Russa Raffaele , Viola Rocco Valerio , D’Errico Stefano , Aromatario Mariarosaria , Maiese Aniello , Anibaldi Paolo , Napoli Christian , Frati Paola , Fineschi Vittorio
Published: March 2021

Over the past two decades, health litigation has followed an exponentially incremental trend. As insurance companies tend to limit their interest because of the high risk of loss, health facilities increasingly need to internalize dispute management. This study was conducted through a retrospective analysis of existing files concerning the civil litigation of the Sant’Andrea Hospital in Rome. All claims from 1 June 2010 to 30 June 2019 were included. Paid claims were further classified according to the areas of health care inappropriateness found. Authors indexed 567 different claims along the study period, with an average number of 59 per year (range 38–77). The total litigation involved 47 different units; more than 40% concerned 5 high-incidence wards or services. Concerning the course of disputes, 91 cases were liquidated before a judicial procedure was instituted, while 177 cases landed in a civil court. Globally, 131 different claims hesitated in compensation, for a total of 16 million 625 thousand euros, 41% of which was related to the internal medicine area. Dealing with the inappropriateness analysis, clinical performance alone involved 76 cases, for a total of 10 million 320 thousand euros, while organization defects involved 20 disputes equivalent to 1 million 788 thousand euros. The aim of this study was to enhance the clinical risk management at our facility through a litigation analysis.
Evaluation of Quality of Life and Satisfaction in Patients with Fixed Prostheses on Zygomatic Implants Compared with the All-on-Four Concept: A Prospective Randomized Clinical Study
Authors: Fernández-Ruiz Juan Alberto , Sánchez-Siles Mariano , Guerrero-Sánchez Yolanda , Pato-Mourelo Jesús , Camacho-Alonso Fabio
Published: March 2021

Purpose: No published research has compared patients’ quality of life and satisfaction with fixed prostheses supported by zygomatic implants with those supported by all-on-four prostheses. The aim of this study was to evaluate patients’ quality of life and satisfaction with fixed prostheses on zygomatic implants compared with the all-on-four concept. Materials and Methods: A total of 80 patients with atrophic edentulous maxillae were randomized into two groups: Group 1 (rehabilitated with fixed prostheses supported by 2–4 zygomatic and 2–4 conventional implants in the anterior region) and Group 2 (fixed prostheses on four implants in the anterior region following an all-on-four concept). One year after placement of the definitive prostheses, patients completed OHIP-14 and satisfaction questionnaires. Results: In all seven domains of the OHIP-14 and in the overall scores, a worse quality of life was found in Group 2 patients, with statistically significant differences between the two groups (p ≤ 0.05). Patients with zygomatic implants were more satisfied with their prostheses, with a statistically significant difference (p < 0.001). Conclusions: According to the results of this study, rehabilitation of patients with edentulous atrophic maxillae with prostheses supported by zygomatic implants combined with anterior implants provided better patient quality of life and satisfaction than prostheses supported by four implants.
On the Origins of Homology Directed Repair in Mammalian Cells
Authors: Sansbury Brett M. , Kmiec Eric B.
Published: March 2021

Over the course of the last five years, expectations surrounding our capacity to selectively modify the human genome have never been higher. The reduction to practice site-specific nucleases designed to cleave at a unique site within the DNA is now centerstage in the development of effective molecular therapies. Once viewed as being impossible, this technology now has great potential and, while cellular and molecular barriers persist to clinical implementations, there is little doubt that these barriers will be crossed, and human beings will soon be treated with gene editing tools. The most ambitious of these desires is the correction of genetic mutations resident within the human genome that are responsible for oncogenesis and a wide range of inherited diseases. The process by which gene editing activity could act to reverse these mutations to wild-type and restore normal protein function has been generally categorized as homology directed repair. This is a catch-all basket term that includes the insertion of short fragments of DNA, the replacement of long fragments of DNA, and the surgical exchange of single bases in the correction of point mutations. The foundation of homology directed repair lies in pioneering work that unravel the mystery surrounding genetic exchange using single-stranded DNA oligonucleotides as the sole gene editing agent. Single agent gene editing has provided guidance on how to build combinatorial approaches to human gene editing using the remarkable programmable nuclease complexes known as Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and their closely associated (Cas) nucleases. In this manuscript, we outline the historical pathway that has helped evolve the current molecular toolbox being utilized for the genetic re-engineering of the human genome.
A 2-Benzylmalonate Derivative as STAT3 Inhibitor Suppresses Tumor Growth in Hepatocellular Carcinoma by Upregulating β-TrCP E3 Ubiquitin Ligase
Authors: Peng Ting , Wonganan Orawan , Zhang Zhonghui , Yu Jialing , Xi Ruiying , Cao Yu , Suksamrarn Apichart , Zhang Guolin , Wang Fei
Published: March 2021

The aberrant activation of a signal transducer and activator of transcription 3 (STAT3) restrains type I interferon (IFN) α/β-induced antiviral responses and is associated with the development of cancer. Designing specific STAT3 inhibitors will thus provide new options for use as IFN therapy. Herein, we identified a novel small molecule, dimethyl 2-(4-(2-(methyl(phenyl(p-tolyl)methyl)amino)ethoxy)benzyl)malonate (CIB-6), which can inhibit the IFN-α-induced interferon stimulated response element (ISRE) luciferase reporter (IC50 value = 6.4 μM) and potentiate the antiproliferative effect of IFN-α in human hepatocellular carcinoma (HCC) cells. CIB-6 was found to bind to the STAT3 Src homology 2 (SH2) domain, thereby selectively inhibiting STAT3 phosphorylation without affecting Janus kinases and STAT1/2. CIB-6 also inhibited the migration and invasion of HCC cells by inhibiting the epithelial–mesenchymal transition (EMT) process. Mechanistically, CIB-6 reduced the expression of β-catenin (an EMT key protein) via upregulating β-transducin repeat-containing protein (β-TrCP) and curbed nuclear factor kappa-B (NF-κB) activation through restricting the phosphorylation of the inhibitor of NF-κB (IκB) kinase (IKK) via STAT3 inhibition. Treatment with CIB-6 significantly retarded tumor growth in nude mice with SK-HEP-1 xenografts. In addition, clinical sample analysis revealed that lower β-TrCP and higher β-catenin expression could affect the median survival time of HCC patients. Our findings suggest that CIB-6 could be a new therapeutic strategy for HCC therapy through STAT3-mediated β-TrCP/β-catenin/NF-κB axis.
Fabrication and Characterisation of a Photo-Responsive, Injectable Nanosystem for Sustained Delivery of Macromolecules
Authors: Mahlumba Pakama , Kumar Pradeep , du Toit Lisa C. , Poka Madan S. , Ubanako Philemon , Choonara Yahya E.
Published: March 2021

The demand for biodegradable sustained release carriers with minimally invasive and less frequent administration properties for therapeutic proteins and peptides has increased over the years. The purpose of achieving sustained minimally invasive and site-specific delivery of macromolecules led to the investigation of a photo-responsive delivery system. This research explored a biodegradable prolamin, zein, modified with an azo dye (DHAB) to synthesize photo-responsive azoprolamin (AZP) nanospheres loaded with Immunoglobulin G (IgG). AZP nanospheres were incorporated in a hyaluronic acid (HA) hydrogel to develop a novel injectable photo-responsive nanosystem (HA-NSP) as a potential approach for the treatment of chorio-retinal diseases such as age-related macular degeneration (AMD) and diabetic retinopathy. AZP nanospheres were prepared via coacervation technique, dispersed in HA hydrogel and characterised via infrared spectroscopy (FTIR), X-ray diffraction (XRD) and thermogravimetric analysis (TGA). Size and morphology were studied via scanning electron microscopy (SEM) and dynamic light scattering (DLS), UV spectroscopy for photo-responsiveness. Rheological properties and injectability were investigated, as well as cytotoxicity effect on HRPE cell lines. Particle size obtained was <200 nm and photo-responsiveness to UV = 365 nm by decreasing particle diameter to 94 nm was confirmed by DLS. Encapsulation efficiency of the optimised nanospheres was 85% and IgG was released over 32 days up to 60%. Injectability of HA-NSP was confirmed with maximum force 10 N required and shear-thinning behaviour observed in rheology studies. In vitro cell cytotoxicity effect of both NSPs and HA-NSP showed non-cytotoxicity with relative cell viability of ≥80%. A biocompatible, biodegradable injectable photo-responsive nanosystem for sustained release of macromolecular IgG was successfully developed.
Beyond the Extracellular Vesicles: Technical Hurdles, Achieved Goals and Current Challenges When Working on Adipose Cells
Authors: Gómez-Serrano María , Ponath Viviane , Preußer Christian , Pogge von Strandmann Elke
Published: March 2021

Adipose tissue and its crosstalk with other organs plays an essential role in the metabolic homeostasis of the entire body. Alteration of this communication (i.e., due to obesity) is related to the development of several comorbidities including type 2 diabetes, cardiovascular diseases, or cancer. Within the adipose depot, adipocytes are the main cell type and thus the main source of secreted molecules, which exert modulating effects not only at a local but also at a systemic level. Extracellular vesicles (EVs) have recently emerged as important mediators in cell–cell communication and account for part of the cellular secretome. In recent years, there has been a growing body of research on adipocyte-derived extracellular vesicles (Ad-EVs). However, there is still a lack of standardized methodological approaches, especially regarding primary adipocytes. In this review, we will provide an outline of crucial aspects when working on adipose-derived material, with a special focus on primary adipocytes. In parallel, we will point out current methodological challenges in the EV field and how they impact the transcriptomic, proteomic and functional evaluations of Ad-EVs.
Machine Learning Reduced Gene/Non-Coding RNA Features That Classify Schizophrenia Patients Accurately and Highlight Insightful Gene Clusters
Authors: Liu Yichuan , Qu Hui-Qi , Chang Xiao , Tian Lifeng , Qu Jingchun , Glessner Joseph , Sleiman Patrick M. A. , Hakonarson Hakon
Published: March 2021

RNA-seq has been a powerful method to detect the differentially expressed genes/long non-coding RNAs (lncRNAs) in schizophrenia (SCZ) patients; however, due to overfitting problems differentially expressed targets (DETs) cannot be used properly as biomarkers. This study used machine learning to reduce gene/non-coding RNA features. Dorsolateral prefrontal cortex (dlpfc) RNA-seq data from 254 individuals was obtained from the CommonMind consortium. The average predictive accuracy for SCZ patients was 67% based on coding genes, and 96% based on long non-coding RNAs (lncRNAs). Machine learning is a powerful algorithm to reduce functional biomarkers in SCZ patients. The lncRNAs capture the characteristics of SCZ tissue more accurately than mRNA as the former regulate every level of gene expression, not limited to mRNA levels.
Therapeutic Potential for Regulation of the Nuclear Factor Kappa-B Transcription Factor p65 to Prevent Cellular Senescence and Activation of Pro-Inflammatory in Mesenchymal Stem Cells
Authors: Mato-Basalo Rocío , Morente-López Miriam , Arntz Onno J , van de Loo Fons A. J. , Fafián-Labora Juan , Arufe María C.
Published: March 2021

Mesenchymal stem cells have an important potential in the treatment of age-related diseases. In the last years, small extracellular vesicles derived from these stem cells have been proposed as cell-free therapies. Cellular senescence and proinflammatory activation are involved in the loss of therapeutic capacity and in the phenomenon called inflamm-aging. The regulators of these two biological processes in mesenchymal stem cells are not well-known. In this study, we found that p65 is activated during cellular senescence and inflammatory activation in human umbilical cord-derived mesenchymal stem cell. To demonstrate the central role of p65 in these two processes, we used small-molecular inhibitors of p65, such as JSH-23, MG-132 and curcumin. We found that the inhibition of p65 prevents the cellular senescence phenotype in human umbilical cord-derived mesenchymal stem cells. Besides, p65 inhibition produced the inactivation of proinflammatory molecules as components of a senescence-associated secretory phenotype (SASP) (interleukin-6 and interleukin-8 (IL-6 and IL-8)). Additionally, we found that the inhibition of p65 prevents the transmission of paracrine senescence between mesenchymal stem cells and the proinflammatory message through small extracellular vesicles. Our work highlights the important role of p65 and its inhibition to restore the loss of functionality of small extracellular vesicles from senescent mesenchymal stem cells and their inflamm-aging signature.
Proteome of Stored RBC Membrane and Vesicles from Heterozygous Beta Thalassemia Donors
Authors: Tzounakas Vassilis L. , Anastasiadi Alkmini T. , Dzieciatkowska Monika , Karadimas Dimitrios G. , Stamoulis Konstantinos , Papassideri Issidora S. , Hansen Kirk C. , D’Alessandro Angelo , Kriebardis Anastasios G. , Antonelou Marianna H.
Published: March 2021

Genetic characteristics of blood donors may impact the storability of blood products. Despite higher basal stress, red blood cells (RBCs) from eligible donors that are heterozygous for beta-thalassemia traits (βThal+) possess a differential nitrogen-related metabolism, and cope better with storage stress compared to the control. Nevertheless, not much is known about how storage impacts the proteome of membrane and extracellular vesicles (EVs) in βThal+. For this purpose, RBC units from twelve βThal+ donors were studied through proteomics, immunoblotting, electron microscopy, and functional ELISA assays, versus units from sex- and aged-matched controls. βThal+ RBCs exhibited less irreversible shape modifications. Their membrane proteome was characterized by different levels of structural, lipid raft, transport, chaperoning, redox, and enzyme components. The most prominent findings include the upregulation of myosin proteoforms, arginase-1, heat shock proteins, and protein kinases, but the downregulation of nitrogen-related transporters. The unique membrane proteome was also mirrored, in part, to that of βThal+ EVs. Network analysis revealed interesting connections of membrane vesiculation with storage and stress hemolysis, along with proteome control modulators of the RBC membrane. Our findings, which are in line with the mild but consistent oxidative stress these cells experience in vivo, provide insight into the physiology and aging of stored βThal+ RBCs.
Covalent Bi-Modular Parallel and Antiparallel G-Quadruplex DNA Nanocostructs Reduce Viability of Patient Glioma Primary Cell Cultures
Authors: Legatova Valeria , Samoylenkova Nadezhda , Arutyunyan Alexander , Tashlitsky Vadim , Zavyalova Elena , Usachev Dmitry , Pavlova Galina , Kopylov Alexey
Published: March 2021

G-quadruplex oligonucleotides (GQs) exhibit specific anti-proliferative activity in human cancer cell lines, and they can selectively inhibit the viability/proliferation of cancer cell lines vs. non-cancer ones. This ability could be translated into a cancer treatment, in particular for glioblastoma multiform (GBM), which currently has a poor prognosis and low-efficiency therapeutic treatments. A novel bi-modular GQ, bi-(AID-1-T), a twin of the previously described three-quartet AID-1-T, was designed and studied in terms of both its structure and function. A covalent conjugation of two AID-1-Ts via three thymidine link, TTT, did not interfere with its initial GQ structure. A comparison of bi-(AID-1-T) with its mono-modular AID-1-T, mono-modular two-quartet HD1, and bi-modular bi-HD1, as well as conventional two-quartet AS1411, was made. Among the five GQs studied, bi-(AID-1-T) had the highest anti-proliferative activity for the neural cancer cell line U87, while not affecting the control cell line, human embryonic fibroblasts. GQs, for the first time, were tested on several primary glioma cultures from patient surgical samples. It turned out that the sensitivity of the patient primary glioma cultures toward GQs varied, with an apparent IC50 of less than 1 μM for bi-(AID-1-T) toward the most sensitive G11 cell culture (glioma, Grade III).
Current State-of-the-Art and Unresolved Problems in Using Human Induced Pluripotent Stem Cell-Derived Dopamine Neurons for Parkinson’s Disease Drug Development
Authors: Antonov S. A. , Novosadova E. V.
Published: March 2021

Human induced pluripotent stem (iPS) cells have the potential to give rise to a new era in Parkinson’s disease (PD) research. As a unique source of midbrain dopaminergic (DA) neurons, iPS cells provide unparalleled capabilities for investigating the pathogenesis of PD, the development of novel anti-parkinsonian drugs, and personalized therapy design. Significant progress in developmental biology of midbrain DA neurons laid the foundation for their efficient derivation from iPS cells. The introduction of 3D culture methods to mimic the brain microenvironment further expanded the vast opportunities of iPS cell-based research of the neurodegenerative diseases. However, while the benefits for basic and applied studies provided by iPS cells receive widespread coverage in the current literature, the drawbacks of this model in its current state, and in particular, the aspects of differentiation protocols requiring further refinement are commonly overlooked. This review summarizes the recent data on general and subtype-specific features of midbrain DA neurons and their development. Here, we review the current protocols for derivation of DA neurons from human iPS cells and outline their general weak spots. The associated gaps in the contemporary knowledge are considered and the possible directions for future research that may assist in improving the differentiation conditions and increase the efficiency of using iPS cell-derived neurons for PD drug development are discussed.
Bioprospecting of Natural Compounds from Brazilian Cerrado Biome Plants in Human Cervical Cancer Cell Lines
Authors: Rosa Marcela N. , e Silva Larissa R. V. , Longato Giovanna B. , Evangelista Adriane F. , Gomes Izabela N. F. , Alves Ana Laura V. , de Oliveira Bruno G. , Pinto Fernanda E. , Romão Wanderson , de Rezende Allisson R. , Araújo Arali A. C. , Oliveira Lohanna S. F. M. , de M. Souza Alessandra A. , Oliveira Stephanie C. , de A. Ribeiro Rosy Iara M. , Silva Viviane A. O. , Reis Rui M.
Published: March 2021

Cervical cancer is the third most common in Brazilian women. The chemotherapy used for the treatment of this disease can cause many side effects; then, to overcome this problem, new treatment options are necessary. Natural compounds represent one of the most promising sources for the development of new drugs. In this study, 13 different species of 6 families from the Brazilian Cerrado vegetation biome were screened against human cervical cancer cell lines (CCC). Some of these species were also evaluated in one normal keratinocyte cell line (HaCaT). The effect of crude extracts on cell viability was evaluated by a colorimetric method (MTS assay). Extracts from Annona crassiflora, Miconia albicans, Miconia chamissois, Stryphnodendron adstringens, Tapirira guianensis, Xylopia aromatica, and Achyrocline alata showed half-maximal inhibitory concentration (IC50) values < 30 μg/mL for at least one CCC. A. crassiflora and S. adstringens extracts were selective for CCC. Mass spectrometry (Electrospray Ionization Fourier Transform Ion Cyclotron Resonance Mass Spectrometer (ESI FT-ICR MS)) of A. crassiflora identified fatty acids and flavonols as secondary compounds. One of the A. crassiflora fractions, 7C24 (from chloroform partition), increased H2AX phosphorylation (suggesting DNA damage), PARP cleavage, and cell cycle arrest in CCC. Kaempferol-3-O-rhamnoside and oleic acid were bioactive molecules identified in 7C24 fraction. These findings emphasize the importance of investigating bioactive molecules from natural sources for developing new anti-cancer drugs.
Ligand-Induced GPR110 Activation Facilitates Axon Growth after Injury
Authors: Kwon Heungsun , Kevala Karl , Xin Hu , Patnaik Samarjit , Marugan Juan , Kim Hee-Yong
Published: March 2021

Recovery from axonal injury is extremely difficult, especially for adult neurons. Here, we demonstrate that the activation of G-protein coupled receptor 110 (GPR110, ADGRF1) is a mechanism to stimulate axon growth after injury. N-docosahexaenoylethanolamine (synaptamide), an endogenous ligand of GPR110 that promotes neurite outgrowth and synaptogenesis in developing neurons, and a synthetic GPR110 ligand stimulated neurite growth in axotomized cortical neurons and in retinal explant cultures. Intravitreal injection of GPR110 ligands following optic nerve crush injury promoted axon extension in adult wild-type, but not in gpr110 knockout, mice. In vitro axotomy or in vivo optic nerve injury rapidly induced the neuronal expression of gpr110. Activating the developmental mechanism of neurite outgrowth by specifically targeting GPR110 that is upregulated upon injury may provide a novel strategy for stimulating axon growth after nerve injury in adults.
Amyloid-Beta Induces Different Expression Pattern of Tissue Transglutaminase and Its Isoforms on Olfactory Ensheathing Cells: Modulatory Effect of Indicaxanthin
Authors: Campisi Agata , Raciti Giuseppina , Sposito Giovanni , Grasso Rosaria , Chiacchio Maria A. , Spatuzza Michela , Attanzio Alessandro , Chiacchio Ugo , Tesoriere Luisa , Allegra Mario , Pellitteri Rosalia
Published: March 2021

Herein, we assessed the effect of full native peptide of amyloid-beta (Aβ) (1-42) and its fragments (25-35 and 35-25) on tissue transglutaminase (TG2) and its isoforms (TG2-Long and TG2-Short) expression levels on olfactory ensheathing cells (OECs). Vimentin and glial fibrillary acid protein (GFAP) were also studied. The effect of the pre-treatment with indicaxanthin from Opuntia ficus-indica fruit on TG2 expression levels and its isoforms, cell viability, total reactive oxygen species (ROS), superoxide anion (O2−), and apoptotic pathway activation was assessed. The levels of Nestin and cyclin D1 were also evaluated. Our findings highlight that OECs exposure to Aβ(1-42) and its fragments induced an increase in TG2 expression levels and a different expression pattern of its isoforms. Indicaxanthin pre-treatment reduced TG2 overexpression, modulating the expression of TG2 isoforms. It reduced total ROS and O2− production, GFAP and Vimentin levels, inhibiting apoptotic pathway activation. It also induced an increase in the Nestin and cyclin D1 expression levels. Our data demonstrated that indicaxanthin pre-treatment stimulated OECs self-renewal through the reparative activity played by TG2. They also suggest that Aβ might modify TG2 conformation in OECs and that indicaxanthin pre-treatment might modulate TG2 conformation, stimulating neural regeneration in Alzheimer’s disease.
Voltage-Based Hybrid Algorithm Using Parameter Variations and Stockwell Transform for Islanding Detection in Utility Grids
Authors: Mahela Om Prakash , Sharma Yagya , Ali Shoyab , Khan Baseem , Garg Akhil Ranjan
Published: March 2021

This paper has introduced an algorithm for the identification of islanding events in the remotely located distribution grid with renewable energy (RE) sources using the voltage signals. Voltage signal is processed using Stockwell transform (ST) to compute the median-based islanding recognition factor (MIRF). The rate of change in the root mean square (RMS) voltage is computed by differentiating the RMS voltage with respect to time to compute the voltage rate of change in islanding recognition factor (VRCIRF). The proposed voltage-based islanding recognition factor (IRFV) is computed by multiplying the MIRF and VRCIRF element to element. The islanding event is discriminated from the faulty and operational events using the simple decision rules using the peak magnitude of IRFV by comparing peak magnitude of IRFV with pre-set threshold values. The proposed islanding detection method (IDM) effectively identified the islanding events in the presence of solar energy, wind energy and simultaneous presence of both wind and solar energy at a fast rate in a time period of less than 0.05 cycles compared to the voltage change rate (ROCOV) and frequency change rate (ROCOF) IDM that detects the islanding event in a time period of 0.25 to 0.5 cycles. This IDM provides a minimum non-detection zone (NDZ). This IDM efficiently discriminated the islanding events from the faulty and switching events. The proposed study is performed on an IEEE-13 bus test system interfaced with renewable energy (RE) generators in a MATLAB/Simulink environment. The performance of the proposed IDM is better compared to methods based on the use of ROCOV, ROCOF and discrete wavelet transform (DWT).
Different Hatching Rates of Floodwater Mosquitoes Aedes sticticus, Aedes rossicus and Aedes cinereus from Different Flooded Environments
Authors: Lindström Anders , Eklöf Disa , Lilja Tobias
Published: March 2021

In the lower Dalälven region, floodwater mosquitoes cause recurring problems. The main nuisance species is Aedes (Ochlerotatus) sticticus, but large numbers of Aedes (Aedes) rossicus and Aedes (Aedes) cinereus also hatch during flooding events. To increase understanding of which environments in the area give rise to mosquito nuisance, soil samples were taken from 20 locations from four environmental categories: grazed meadows, mowed meadows, unkept open grassland areas and forest areas. In each location 20 soil samples were taken, 10 from random locations and 10 from moisture retaining structures, such as tussocks, shrubs, piles of leaves, logs, and roots. The soil samples were soaked with tap water in the lab, and mosquito larvae were collected and allowed to develop to adult mosquitoes for species identification. Fewer larvae hatched from mowed areas and more larvae hatched from moisture retaining structure samples than random samples. The results showed that Aedes cinereus mostly hatch from grazed and unkept areas and hatched as much from random samples as from structures, whereas Aedes sticticus and Aedes rossicus hatched from open unkept and forest areas and hatch significantly more from structure samples. When the moisture retaining structures in open unkept areas where Aedes sticticus hatched were identified it was clear that they hatched predominantly from willow shrubs that offered shade. The results suggest that Ae. sticticus and Ae. cinereus favor different flooded environments for oviposition.
Impact of Comingled Heterospecific Assemblages on Developmentally Based Estimates of the Post-Mortem Interval—A Study with Lucilia sericata (Meigen), Phormia regina (Meigen) and Calliphora vicina Robineau-Desvoidy (Diptera: Calliphoridae)
Authors: Hans Krystal R. , Vanlaerhoven Sherah L.
Published: March 2021

Estimates of the minimum post-mortem interval (mPMI) using the development rate of blow flies (Diptera: Calliphoridae) are common in modern forensic entomology casework. These estimates are based on single species developing in the absence of heterospecific interactions. Yet, in real-world situations, it is not uncommon to have 2 or more blow fly species developing on a body. Species interactions have the potential to change the acceptance of resources as suitable for oviposition, the timing of oviposition, growth rate, size and development time of immature stages, as well as impacting the survival of immature stages to reach adult. This study measured larval development and growth rate of the blow flies Lucilia sericata (Meigen, 1826), Phormia regina (Meigen, 1826) and Calliphora vicina Robineau-Desvoidy (Diptera: Calliphoridae) over five constant temperatures (15, 20, 25, 30, 35 °C), in the presence of conspecifics or two-species heterospecific assemblages. Temperature and species treatment interacted such that L. sericata larvae gained mass more rapidly when in the presence of P. regina at 20 and 30 °C, however only developed faster at first instar. At later stages, the presence of P. regina slowed development of L. sericata immatures. Development time of C. vicina immatures was not affected by the presence of P. regina, however larvae gained mass more slowly. Development time of P. regina immatures was faster in the presence of either L. sericata or C. vicina until third instar, at which point, the presence of L. sericata was neutral whereas C. vicina negatively impacted development time. Phormia regina larvae gained mass more rapidly in the presence of L. sericata at 20 °C but were negatively impacted at 25 °C by the presence of either L. sericata or C. vicina. The results of this study indicate that metrics such as development time or larval mass used for estimating mPMI with blow flies are impacted by the presence of comingled heterospecific blow fly assemblages. As the effects of heterospecific assemblages are not uniformly positive or negative between stages, temperatures or species combinations, more research into these effects is vital. Until then, caution should be used when estimating mPMI in cases with multiple blow fly species interacting on a body.
The Forensic Entomology Case Report—A Global Perspective
Authors: Kotzé Zanthé , Aimar Sylvain , Amendt Jens , Anderson Gail S. , Bourguignon Luc , Hall Martin J.R. , Tomberlin Jeffery K.
Published: March 2021

Forensic practitioners analyzing entomological evidence are faced with numerous challenges when presenting their findings to law practitioners, particularly in terms of terminology used to describe insect age, what this means for colonization time of remains, and the limitations to estimates made. Due to varying legal requirements in different countries, there is no standard format for the entomological case report prepared, nor any guidelines as to the sections that are required, optional or unnecessary in a case report. The authors herein propose sections that should be considered when drafting an entomological case report. The criteria under which entomological evidence is analyzed are discussed, as well as the limitations for each criterion. The concept of a global, standardized entomological case report is impossible to achieve due to national legislative differences, but the authors here propose a basic template which can be adapted and changed according to the needs of the practitioner. Furthermore, while the discussion is fairly detailed, capturing all differences between nations could not be accomplished, and those initiating casework for the first time are encouraged to engage other practicing forensic entomologists or professional associations within their own nation or region, to ensure a complete report is generated that meets lab or national requirements, prior to generating a finalized report.
A Robust Interval Type-2 Fuzzy Logic Controller for Variable Speed Wind Turbines Based on a Doubly Fed Induction Generator
Authors: Hemeyine Ahmed Vall , Abbou Ahmed , Bakouri Anass , Mokhlis Mohcine , El Moustapha Sidi Mohamed ould Mohamed
Published: March 2021

This paper presents an implementation of a new robust control strategy based on an interval type-2 fuzzy logic controller (IT2-FLC) applied to the wind energy conversion system (WECS). The wind generator used was a variable speed wind turbine based on a doubly fed induction generator (DFIG). Fuzzy logic concepts have been applied with great success in many applications worldwide. So far, the vast majority of systems have used type-1 fuzzy logic controllers. However, T1-FLC cannot handle the high level of uncertainty in systems (complex and non-linear systems). The amount of uncertainty in a system could be reduced by using type-2 fuzzy logic since it offers better capabilities to handle linguistic uncertainties by modeling vagueness and unreliability of information. A new concept based on an interval type-2 fuzzy logic controller (IT-2 FLC) was developed because of its uncertainty management capabilities. Both these control strategies were designed and their performances compared for the purpose of showing the control most efficient in terms of reference tracking and robustness. We made a comparison between the performance of the type-1 fuzzy logic controller (T1-FLC) and interval type-2 fuzzy logic controller (IT2-FLC). The simulation results clearly manifest the height robustness of the interval type-2 fuzzy logic controller in comparison to the T1-FLC in terms of rise time, settling time, and overshoot value. The simulations were realized by MATLAB/Simulink software.
Opiophobia in Emergency Department Healthcare Providers: A Survey in Western Switzerland
Authors: Bertrand Sarah , Meynet Gabriel , Taffé Patrick , Della Santa Vincent , Fishman Daniel , Fournier Yvan , Frochaux Vincent , Ribordy Vincent , Rutschmann Olivier T. , Hugli Olivier
Published: March 2021

Opiophobia contributes to oligoanalgesia in the emergency department (ED), but its definition varies, and its association to healthcare providers’ personality traits has been scantly explored. Our purpose was to study the different definitions of opiophobia and their association with two personality traits of doctors and nurses working in EDs, namely the stress from uncertainty and risk-taking. We used three online questionnaires: the ‘Attitude Towards Morphine Use’ Score (ATMS), the Stress From Uncertainty Scale (SUS) and the Risk-Taking Scale (RTS). Doctors and nurses from nine hospital EDs in francophone Switzerland were invited to participate. The ATMS score was analyzed according to demographic characteristics, SUS, and RTS. The response rate was 56%, with 57% of respondents being nurses and 63% women. Doctors, less experienced and non-indigenous participants had a significantly higher ATMS (all p ≤ 0.01). The main contributors of the ATMS were the fear of side effects and of addiction. In multivariate analysis, being a doctor, less experience and non-indigenous status were predictive of the ATMS; each point of the SUS increased the ATMS by 0.24 point. The fear of side effects and of addiction were the major contributors of opiophobia among ED healthcare providers; opiophobia was also associated with their personality traits.
Resting Heart Rate as a Predictor of Cancer Mortality: A Systematic Review and Meta-Analysis
Authors: Pozuelo-Carrascosa Diana P. , Cavero-Redondo Iván , Lee I.M. , Álvarez-Bueno Celia , Reina-Gutierrez Sara , Martínez-Vizcaíno Vicente
Published: March 2021

This work was aimed to synthetize the evidence available about the relationship between resting heart rate (RHR) and the risk of cancer mortality. A computerized search in the Medline, EMBASE, Web of Science, and Cochrane Library databases from their inception to 24 September 2020 was performed. We performed three meta-analyses: (1) cancer mortality comparing the “less than 60 bpm” and “more than 60 bpm” categories; (2) cancer mortality comparing “less than 60 bpm”, “60 to 80 bpm”, and “more than 80 bpm” categories; and (3) analysis for 10–12 and 20 bpm increase in RHR and risk of cancer mortality. Twenty-two studies were included in the qualitative review, and twelve of them met the inclusion criteria for the meta-analysis. Our results showed a positive association between RHR and the risk of cancer mortality. This association was shown in a meta-analysis comparing studies reporting mean RHR values below and above 60 bpm, when comparing three RHR categories using less than 60 bpm as the reference category and, finally, in dose response analyses estimating the effect of an increase of 10–12 bpm in RHR, both in men and in women. In conclusion, a low RHR is a potential marker of low risk of cancer mortality.
Nano-Encapsulation of Mithramycin in Transfersomes and Polymeric Micelles for the Treatment of Sarcomas
Authors: Estupiñán Óscar , Rendueles Claudia , Suárez Paula , Rey Verónica , Murillo Dzohara , Morís Francisco , Gutiérrez Gemma , Blanco-López María del Carmen , Matos María , Rodríguez René
Published: March 2021

Sarcomas are aggressive tumors which often show a poor response to current treatments. As a promising therapeutic alternative, we focused on mithramycin (MTM), a natural antibiotic with a promising anti-tumor activity but also a relevant systemic toxicity. Therefore, the encapsulation of MTM in nano-delivery systems may represent a way to increase its therapeutic window. Here, we designed novel transfersomes and PLGA polymeric micelles by combining different membrane components (phosphatidylcholine, Span 60, Tween 20 and cholesterol) to optimize the nanoparticle size, polydispersity index (PDI) and encapsulation efficiency (EE). Using both thin film hydration and the ethanol injection methods we obtained MTM-loaded transferosomes displaying an optimal hydrodynamic diameter of 100–130 nm and EE values higher than 50%. Additionally, we used the emulsion/solvent evaporation method to synthesize polymeric micelles with a mean size of 228 nm and a narrow PDI, capable of encapsulating MTM with EE values up to 87%. These MTM nano-delivery systems mimicked the potent anti-tumor activity of free MTM, both in adherent and cancer stem cell-enriched tumorsphere cultures of myxoid liposarcoma and chondrosarcoma models. Similarly to free MTM, nanocarrier-delivered MTM efficiently inhibits the signaling mediated by the pro-oncogenic factor SP1. In summary, we provide new formulations for the efficient encapsulation of MTM which may constitute a safer delivering alternative to be explored in future clinical uses.
Progressive Sarcopenia Correlates with Poor Response and Outcome to Immune Checkpoint Inhibitor Therapy
Authors: Loosen Sven H. , van den Bosch Vincent , Gorgulho Joao , Schulze-Hagen Maximilian , Kandler Jennis , Jördens Markus S. , Tacke Frank , Loberg Christina , Antoch Gerald , Brümmendorf Tim , Neumann Ulf P. , Kuhl Christiane , Luedde Tom , Roderburg Christoph
Published: March 2021

Background: Immune checkpoint inhibitors (ICIs) represent a new therapeutic standard for an increasing number of tumor entities. Nevertheless, individual response and outcome to ICI is very heterogeneous, and the identification of the ideal ICI candidate has remained one of the major issues. Sarcopenia and the progressive loss of muscle mass and strength, as well as muscular fat deposition, have been established as negative prognostic factors for a variety of diseases, but their role in the context of ICI therapy is not fully understood. Here, we have evaluated skeletal muscle composition as a novel prognostic marker in patients undergoing ICI therapy for solid malignancies. Methods: We analyzed patients with metastasized cancers receiving ICI therapy according to the recommendation of the specific tumor board. Routine CT scans before treatment initialization and during ICI therapy were used to assess the skeletal muscle index (L3SMI) as well as the mean skeletal muscle attenuation (MMA) in n = 88 patients receiving ICI therapy. Results: While baseline L3SMI and MMA values were unsuitable for predicting the individual response and outcome to ICI therapy, longitudinal changes of the L3SMI and MMA (∆L3SMI, ∆MMA) during ICI therapy turned out to be a relevant marker of therapy response and overall survival. Patients who responded to ICI therapy at three months had a significantly higher ∆L3SMI compared to non-responders (−3.20 mm2/cm vs. 1.73 mm2/cm, p = 0.002). Moreover, overall survival (OS) was significantly lower in patients who had a strongly decreasing ∆L3SMI (<−6.18 mm2/cm) or a strongly decreasing ∆MMA (<−0.4 mm2/cm) during the first three month of ICI therapy. Median OS was only 127 days in patients with a ∆L3SMI of below −6.18 mm2/cm, compared to 547 days in patients with only mildly decreasing or even increasing ∆L3SMI values (p < 0.001). Conclusion: Both progressive sarcopenia and an increasing skeletal muscle fat deposition are associated with poor response and outcome to ICI therapy, which might help to guide treatment decisions during ICI therapy.
Clinical Origin and Species Distribution of Fusarium spp. Isolates Identified by Molecular Sequencing and Mass Spectrometry: A European Multicenter Hospital Prospective Study
Authors: Normand Anne-Cécile , Imbert Sébastien , Brun Sophie , Al-Hatmi Abdullah M. S. , Chryssanthou Erja , Cassaing Sophie , Schuttler Christine , Hasseine Lilia , Mahinc Caroline , Costa Damien , Bonnal Christine , Ranque Stéphane , Sautour Marc , Rubio Elisa , Delhaes Laurence , Riat Arnaud , Sendid Boualem , Kristensen Lise , Brandenberger Marcel , Guitard Juliette , Packeu Ann , Piarroux Renaud , Fekkar Arnaud
Published: March 2021

Fusarium spp. are widespread environmental fungi as well as pathogens that can affect plants, animals and humans. Yet the epidemiology of human fusariosis is still cloudy due to the rapidly evolving taxonomy. The Mass Spectrometry Identification database (MSI) has been developed since 2017 in order to allow a fast, accurate and free-access identification of fungi by matrix-assisted laser desorption ionization—time of flight (MALDI-TOF) mass spectrometry. Taking advantage of the MSI database user network, we aim to study the species distribution of Fusarium spp. isolates in an international multicenter prospective study. This study also allowed the assessment of the abilities of miscellaneous techniques to identify Fusarium isolates at the species level. The identification was performed by PCR-sequencing and phylogenic-tree approach. Both methods are used as gold standard for the evaluation of mass spectrometry. Identification at the species complex was satisfactory for all the tested methods. However, identification at the species level was more challenging and only 32% of the isolates were correctly identified with the National Center for Biotechnology Information (NCBI) DNA database, 20% with the Bruker MS database and 43% with the two MSI databases. Improvement of the mass spectrometry database is still needed to enable precise identification at the species level of any Fusarium isolates encountered either in human pathology or in the environment.
Cropland Abandonment in Slovakia: Analysis and Comparison of Different Data Sources
Authors: Lieskovský Juraj , Lieskovská Dana
Published: March 2021

This study compares different nationwide multi-temporal spatial data sources and analyzes the cropland area, cropland abandonment rates and transformation of cropland to other land cover/land use categories in Slovakia. Four multi-temporal land cover/land use data sources were used: The Historic Land Dynamics Assessment (HILDA), the Carpathian Historical Land Use Dataset (CHLUD), CORINE Land Cover (CLC) data and Landsat images classification. We hypothesized that because of the different spatial, temporal and thematic resolution of the datasets, there would be differences in the resulting cropland abandonment rates. We validated the datasets, compared the differences, interpreted the results and combined the information from the different datasets to form an overall picture of long-term cropland abandonment in Slovakia. The cropland area increased until the Second World War, but then decreased after transition to the communist regime and sharply declined following the 1989 transition to an open market economy. A total of 49% of cropland area has been transformed to grassland, 34% to forest and 15% to urban areas. The Historical Carpathian dataset is the more reliable long-term dataset, and it records 19.65 km2/year average cropland abandonment for 1836–1937, 154.44 km2/year for 1938–1955 and 140.21 km2/year for 1956–2012. In comparison, the Landsat, as a recent data source, records 142.02 km2/year abandonment for 1985–2000 and 89.42 km2/year for 2000–2010. These rates, however, would be higher if the dataset contained urbanisation data and more precise information on afforestation. The CORINE Land Cover reflects changes larger than 5 ha, and therefore the reported cropland abandonment rates are lower.