bluuebunny/crossref_metadata_2025 huggingface dataset:
Are Strategies Favoring Pattern Matching a Viable Way to Improve Complexity Estimation Based on Sample Entropy?
Authors: Porta Alberto , Valencia José Fernando , Cairo Beatrice , Bari Vlasta , De Maria Beatrice , Gelpi Francesca , Barbic Franca , Furlan Raffaello
Published: June 2020

It has been suggested that a viable strategy to improve complexity estimation based on the assessment of pattern similarity is to increase the pattern matching rate without enlarging the series length. We tested this hypothesis over short simulations of nonlinear deterministic and linear stochastic dynamics affected by various noise amounts. Several transformations featuring a different ability to increase the pattern matching rate were tested and compared to the usual strategy adopted in sample entropy (SampEn) computation. The approaches were applied to evaluate the complexity of short-term cardiac and vascular controls from the beat-to-beat variability of heart period (HP) and systolic arterial pressure (SAP) in 12 Parkinson disease patients and 12 age- and gender-matched healthy subjects at supine resting and during head-up tilt. Over simulations, the strategies estimated a larger complexity over nonlinear deterministic signals and a greater regularity over linear stochastic series or deterministic dynamics importantly contaminated by noise. Over short HP and SAP series the techniques did not produce any practical advantage, with an unvaried ability to discriminate groups and experimental conditions compared to the traditional SampEn. Procedures designed to artificially increase the number of matches are of no methodological and practical value when applied to assess complexity indexes.
Effective DGA-Domain Detection and Classification with TextCNN and Additional Features
Authors: Hwang Chanwoong , Kim Hyosik , Lee Hooki , Lee Taejin
Published: June 2020

Malicious codes, such as advanced persistent threat (APT) attacks, do not operate immediately after infecting the system, but after receiving commands from the attacker’s command and control (C&C) server. The system infected by the malicious code tries to communicate with the C&C server through the IP address or domain address of the C&C server. If the IP address or domain address is hard-coded inside the malicious code, it can analyze the malicious code to obtain the address and block access to the C&C server through security policy. In order to circumvent this address blocking technique, domain generation algorithms are included in the malware to dynamically generate domain addresses. The domain generation algorithm (DGA) generates domains randomly, so it is very difficult to identify and block malicious domains. Therefore, this paper effectively detects and classifies unknown DGA domains. We extract features that are effective for TextCNN-based label prediction, and add additional domain knowledge-based features to improve our model for detecting and classifying DGA-generated malicious domains. The proposed model achieved 99.19% accuracy for DGA classification and 88.77% accuracy for DGA class classification. We expect that the proposed model can be applied to effectively detect and block DGA-generated domains.
Multi-Objective Fuzzy Logic-Based Energy Management System for Microgrids with Battery and Hydrogen Energy Storage System
Authors: Vivas Francisco José , Segura Francisca , Andújar José Manuel , Palacio Adriana , Saenz Jaime Luis , Isorna Fernando , López Eduardo
Published: June 2020

This paper proposes a fuzzy logic-based energy management system (EMS) for microgrids with a combined battery and hydrogen energy storage system (ESS), which ensures the power balance according to the load demand at the time that it takes into account the improvement of the microgrid performance from a technical and economic point of view. As is known, renewable energy-based microgrids are receiving increasing interest in the research community, since they play a key role in the challenge of designing the next energy transition model. The integration of ESSs allows the absorption of the energy surplus in the microgrid to ensure power supply if the renewable resource is insufficient and the microgrid is isolated. If the microgrid can be connected to the main power grid, the freedom degrees increase and this allows, among other things, diminishment of the ESS size. Planning the operation of renewable sources-based microgrids requires both an efficient dispatching management between the available and the demanded energy and a reliable forecasting tool. The developed EMS is based on a fuzzy logic controller (FLC), which presents different advantages regarding other controllers: It is not necessary to know the model of the plant, and the linguistic rules that make up its inference engine are easily interpretable. These rules can incorporate expert knowledge, which simplifies the microgrid management, generally complex. The developed EMS has been subjected to a stress test that has demonstrated its excellent behavior. For that, a residential-type profile in an actual microgrid has been used. The developed fuzzy logic-based EMS, in addition to responding to the required load demand, can meet both technical (to prolong the devices’ lifespan) and economic (seeking the highest profitability and efficiency) established criteria, which can be introduced by the expert depending on the microgrid characteristic and profile demand to accomplish.
High Efficiency Ring-LWE Cryptoprocessor Using Shared Arithmetic Components
Authors: Nguyen Tan Tuy , Thi Bao Nguyen Tram , Lee Hanho
Published: June 2020

A high efficiency architecture for ring learning with errors (ring-LWE) cryptoprocessor using shared arithmetic components is presented in this paper. By applying a novel approach for sharing number theoretic transform (NTT) polynomial multiplier and polynomial adder in encryption and decryption operations, the total number of polynomial multipliers and polynomial adders used in the proposed ring-LWE cryptoprocessor are reduced. In addition, the processing time of NTT polynomial multiplier is speeded up by employing multiple-path delay feedback (MDF) architecture and deploying pipelined technique between all stages of NTT processes. As a result, the proposed architecture offers a great reduction in terms of the hardware complexity and computation latency compared with existing works. The implementation result for the proposed ring-LWE cryptoprocessor on Virtex-7 FPGA board using Xilinx VIVADO shows a significant decrease in the number of slices and LUTs compared with previous works. Moreover, the proposed ring-LWE cryptoprocessor offers higher throughput and efficiency than its predecessors.
Bitcoin’s APIs in Open-Source Projects: Security Usability Evaluation
Authors: Tschannen Philipp , Ahmed Ali
Published: June 2020

Given the current state of software development, it does not seem that we are nowhere near vulnerability-free software applications, due to many reasons, and software developers are one of them. Insecure coding practices, the complexity of the task in hand, and usability issues, amongst other reasons, make it hard on software developers to maintain secure code. When it comes to cryptographic currencies, the need for assuring security is inevitable. For example, Bitcoin is a peer-to-peer software system that is primarily used as digital money. There exist many software libraries supporting various programming languages that allow access to the Bitcoin system via an Application Programming Interface (API). APIs that are inappropriately used would lead to security vulnerabilities, which are hard to discover, resulting in many zero-day exploits. Making APIs usable is, therefore, an essential aspect related to the quality and robustness of the software. This paper surveys the general academic literature concerning API usability and usable security. Furthermore, it evaluates the API usability of Libbitcoin, a well-known C++ implementation of the Bitcoin system, and assesses how the findings of this evaluation could affect the applications that use Libbitcoin. For that purpose, the paper proposes two static analysis tools to further investigate the use of Libbitcoin APIs in open-source projects from a security usability perspective. The findings of this research have improved Libbitcoin in many places, as will be shown in this paper.
A Preliminary Report for the Design of MoS (Micro-Olive-Spreadsheet), a User-Friendly Spreadsheet for the Evaluation of the Microbiological Quality of Spanish-Style Bella di Cerignola Olives from Apulia (Southern Italy)
Authors: Bevilacqua Antonio , Speranza Barbara , Campaniello Daniela , Sinigaglia Milena , Corbo Maria Rosaria
Published: June 2020

A user friendly spreadsheet (Excel interface), designated MoS (Micro-Olive-Spreadsheet), is proposed in this paper as a tool to point out spoiling phenomena in Bella di Cerignola olive brines. The spreadsheet was designed as a protected Excel worksheet, where users input values for the microbiological criteria and pH of brines, and the output is a visual code, much like a traffic light: three red cells indicate a spoiling event, while two red cells indicate the possibility of a spoiling event. The input values are: (a) Total Aerobic Count (TAC); (b) Lactic Acid Bacteria (LAB); (c) yeasts; (d) staphylococci; (e) pH. TAC, LAB, yeasts, and pH are the input values for the first section (quality), while staphylococci count is the input for the second section (technological history). The worksheet can be modified by adding other indices or by setting different breakpoints; however, it is a simple tool for an effective application of hazard analysis and predictive microbiology in table olive production.
Thyme Antimicrobial Effect in Edible Films with High Pressure Thermally Treated Whey Protein Concentrate
Authors: Bleoancă Iulia , Enachi Elena , Borda Daniela
Published: June 2020

Application of high pressure-thermal treatment (600 MPa and 70 °C, 20 min) for obtaining edible films functionalized with thyme extracts have been studied in order to evaluate the antimicrobial capacity of films structure to retain and release the bioactive compounds. The high pressure-thermally treated films (HPT) were compared with the thermally treated (TT) ones (80 ± 0.5 °C, 35 min). The film structures were analyzed and the sorption isotherms, water vapor permeability, antimicrobial activity and the volatile fingerprints by GC/MS were performed. The HPT film presented more binding sites for water chemi-sorption than TT films and displayed significantly lower WVP than TT films (p < 0.05). TT films displayed slightly, but significant higher, antimicrobial activity (p < 0.05) against Geotrichum candidum in the first day and against Bacillus subtilis in the 10th day of storage. The HPT film structure had ~1.5-fold higher capacity to retain volatiles after drying compared to TT films. From the HPT films higher amount of p-cymene and α-terpinene was volatilized during 10 days of storage at 25 °C, 50% RH while from the TT films higher amount of caryophyllene and carvacrol were released. During storage HPT films had a 2-fold lower capacity to retain monoterpenes compared to TT films.
Extensive Involvement of Alternative Polyadenylation in Single-Nucleus Neurons
Authors: Wang Ying , Feng Weixing , Xu Siwen , He Bo
Published: June 2020

Cleavage and polyadenylation are essential processes that can impact many aspects of mRNA fate. Most eukaryotic genes have alternative polyadenylation (APA) events. While the heterogeneity of mRNA polyadenylation isoform choice has been studied in specific tissues, less attention has been paid to the neuronal heterogeneity of APA selection at single-nucleus resolution. APA is highly controlled during development and neuronal activation, however, to what extent APA events vary in a specific neuronal cell population and the regulatory mechanisms are still unclear. In this paper, we investigated dynamic APA usage in different cell types using snRNA-seq data of 1424 human brain cells generated by single-cell 3′ RNA sequencing. We found that distal APA sites are not only favored by global neuronal cells, but that their usage also varies between the principal types of neuronal cell populations (excitatory neurons and inhibitory neurons). A motif analysis and a gene functional analysis indicated the enrichment of RNA-binding protein (RBP) binding sites and neuronal functions for the set of genes with neuron-enhanced distal PAS usage. Our results revealed the extensive involvement of APA regulation in neuronal populations at the single-nucleus level, providing new insights into roles for APA in specific neuronal cell populations, as well as utility in future functional studies.
Omics Approaches Applied to Penicillium chrysogenum and Penicillin Production: Revealing the Secrets of Improved Productivity
Authors: García-Estrada Carlos , Martín Juan F. , Cueto Laura , Barreiro Carlos
Published: June 2020

Penicillin biosynthesis by Penicillium chrysogenum is one of the best-characterized biological processes from the genetic, molecular, biochemical, and subcellular points of view. Several omics studies have been carried out in this filamentous fungus during the last decade, which have contributed to gathering a deep knowledge about the molecular mechanisms underlying improved productivity in industrial strains. The information provided by these studies is extremely useful for enhancing the production of penicillin or other bioactive secondary metabolites by means of Biotechnology or Synthetic Biology.
Of Drugs and Trypanosomatids: New Tools and Knowledge to Reduce Bottlenecks in Drug Discovery
Authors: Bhattacharya Arijit , Corbeil Audrey , do Monte-Neto Rubens L. , Fernandez-Prada Christopher
Published: June 2020

Leishmaniasis (Leishmania species), sleeping sickness (Trypanosoma brucei), and Chagas disease (Trypanosoma cruzi) are devastating and globally spread diseases caused by trypanosomatid parasites. At present, drugs for treating trypanosomatid diseases are far from ideal due to host toxicity, elevated cost, limited access, and increasing rates of drug resistance. Technological advances in parasitology, chemistry, and genomics have unlocked new possibilities for novel drug concepts and compound screening technologies that were previously inaccessible. In this perspective, we discuss current models used in drug-discovery cascades targeting trypanosomatids (from in vitro to in vivo approaches), their use and limitations in a biological context, as well as different examples of recently discovered lead compounds.
CDK Regulation of Meiosis: Lessons from S. cerevisiae and S. pombe
Authors: MacKenzie Anne M. , Lacefield Soni
Published: June 2020

Meiotic progression requires precise orchestration, such that one round of DNA replication is followed by two meiotic divisions. The order and timing of meiotic events is controlled through the modulation of the phosphorylation state of proteins. Key components of this phospho-regulatory system include cyclin-dependent kinase (CDK) and its cyclin regulatory subunits. Over the past two decades, studies in budding and fission yeast have greatly informed our understanding of the role of CDK in meiotic regulation. In this review, we provide an overview of how CDK controls meiotic events in both budding and fission yeast. We discuss mechanisms of CDK regulation through post-translational modifications and changes in the levels of cyclins. Finally, we highlight the similarities and differences in CDK regulation between the two yeast species. Since CDK and many meiotic regulators are highly conserved, the findings in budding and fission yeasts have revealed conserved mechanisms of meiotic regulation among eukaryotes.
Expression Analysis and Serodiagnostic Potential of Microneme Proteins 1 and 3 in Eimeria stiedai
Authors: Wei Wenrui , Shen Nengxing , Xiao Jie , Tao Yuanyuan , Luo Yuejun , Angel Christiana , Gu Xiaobin , Xie Yue , He Ran , Jing Bo , Peng Xuerong , Yang Guangyou
Published: June 2020

Eimeria stiedai is an apicomplexan protozoan parasite that invades the liver and bile duct epithelial cells in rabbits and causes severe hepatic coccidiosis, resulting in significant economic losses in the domestic rabbit industry. Hepatic coccidiosis lacks the typical clinical symptoms and there is a lack of effective premortem tools to timely diagnose this disease. Therefore, in the present study we cloned and expressed the two microneme proteins i.e., microneme protein 1 (EsMIC1) and microneme protein 3 (EsMIC3) from E. stiedai and used them as recombinant antigens to develop a serodiagnostic method for an effective diagnosis of hepatic coccidiosis. The cDNAs encoding EsMIC1 and EsMIC3 were cloned and the mRNA expression levels of these two genes at different developmental stages of E. stiedai were determined by quantitative real-time PCR analysis (qRT-PCR). The immunoreactivity of recombinant EsMIC1 (rEsMIC1) and EsMIC3 (rEsMIC3) proteins were detected by Western blotting, and indirect enzyme-linked immunosorbent assays (ELISAs) based on these two recombinant antigens were established to evaluate their serodiagnostic potential. Our results showed that the proteins encoded by the ORFs of EsMIC1 (711 bp) and EsMIC3 (891 bp) were approximately 25.89 and 32.39 kDa in predicted molecular weight, respectively. Both EsMIC1 and EsMIC3 showed the highest mRNA expression levels in the merozoites stage of E. stiedai. Western blotting analysis revealed that both recombinant proteins were recognized by E. stiedai positive sera, and the indirect ELISAs using rEsMIC1 and rEsMIC3 were developed based on their good immunoreactivity, with 100% (48/48) sensitivity and 97.9% (47/48) specificity for rEsMIC1 with 100% (48/48) sensitivity and 100% (48/48) specificity for rEsMIC3, respectively. Moreover, rEsMIC1- and rEsMIC3-based indirect ELISA were able to detect corresponding antibodies in sera at days 6, 8, and 10 post E. stiedai infection, with the highest positive diagnostic rate (62.5% (30/48) for rEsMIC1 and 66.7% (32/48) for rEsMIC3) observed at day 10 post infection. Therefore, both EsMIC1 and EsMIC3 can be used as potential serodiagnostic candidate antigens for hepatic coccidiosis caused by E. stiedai.
Utility of Common Marmoset (Callithrix jacchus) Embryonic Stem Cells in Liver Disease Modeling, Tissue Engineering and Drug Metabolism
Authors: Aravalli Rajagopal N. , Steer Clifford J.
Published: June 2020

The incidence of liver disease is increasing significantly worldwide and, as a result, there is a pressing need to develop new technologies and applications for end-stage liver diseases. For many of them, orthotopic liver transplantation is the only viable therapeutic option. Stem cells that are capable of differentiating into all liver cell types and could closely mimic human liver disease are extremely valuable for disease modeling, tissue regeneration and repair, and for drug metabolism studies to develop novel therapeutic treatments. Despite the extensive research efforts, positive results from rodent models have not translated meaningfully into realistic preclinical models and therapies. The common marmoset Callithrix jacchus has emerged as a viable non-human primate model to study various human diseases because of its distinct features and close physiologic, genetic and metabolic similarities to humans. C. jacchus embryonic stem cells (cjESC) and recently generated cjESC-derived hepatocyte-like cells (cjESC-HLCs) could fill the gaps in disease modeling, liver regeneration and metabolic studies. They are extremely useful for cell therapy to regenerate and repair damaged liver tissues in vivo as they could efficiently engraft into the liver parenchyma. For in vitro studies, they would be advantageous for drug design and metabolism in developing novel drugs and cell-based therapies. Specifically, they express both phase I and II metabolic enzymes that share similar substrate specificities, inhibition and induction characteristics, and drug metabolism as their human counterparts. In addition, cjESCs and cjESC-HLCs are advantageous for investigations on emerging research areas, including blastocyst complementation to generate entire livers, and bioengineering of discarded livers to regenerate whole livers for transplantation.
Protective Mechanisms Against DNA Replication Stress in the Nervous System
Authors: Forrer Charlier Clara , Martins Rodrigo A. P.
Published: June 2020

The precise replication of DNA and the successful segregation of chromosomes are essential for the faithful transmission of genetic information during the cell cycle. Alterations in the dynamics of genome replication, also referred to as DNA replication stress, may lead to DNA damage and, consequently, mutations and chromosomal rearrangements. Extensive research has revealed that DNA replication stress drives genome instability during tumorigenesis. Over decades, genetic studies of inherited syndromes have established a connection between the mutations in genes required for proper DNA repair/DNA damage responses and neurological diseases. It is becoming clear that both the prevention and the responses to replication stress are particularly important for nervous system development and function. The accurate regulation of cell proliferation is key for the expansion of progenitor pools during central nervous system (CNS) development, adult neurogenesis, and regeneration. Moreover, DNA replication stress in glial cells regulates CNS tumorigenesis and plays a role in neurodegenerative diseases such as ataxia telangiectasia (A-T). Here, we review how replication stress generation and replication stress response (RSR) contribute to the CNS development, homeostasis, and disease. Both cell-autonomous mechanisms, as well as the evidence of RSR-mediated alterations of the cellular microenvironment in the nervous system, were discussed.
The Role of Expanded Polystyrene and Geocell in Enhancing the Behavior of Buried HDPE Pipes under Trench Loading Using Numerical Analyses
Authors: Khalaj Omid , Azizian Mehran , Joz Darabi Naser , Moghaddas Tafreshi Seyed Naser , Jirková Hana
Published: June 2020

In recent years, much research has focused on the use of various materials for relieving and strengthening soil, e.g., steel reinforcing ribs, geosynthetics, geocell, waste tires, and expanded polystyrene (EPS). EPS is being used increasingly in geo-infrastructure, being a super-light material, to replace part of the soil and decrease the ground pressure on buried structures. This paper presents experimental and numerical analyses of the effectiveness of expanded polystyrene and geocell reinforcement for ameliorating the behavior of unpressurized buried pipes exposed to surface loading. A 3-D finite element method (FEM) model of soil, geofoam, geocell, and piping was generated in ABAQUS, and the model was verified by experimental analyses conducted at a laboratory. The results show that reinforcing the soil cover with geocell and geofoam has a substantial impact, decreasing the maximum surface settlement by around 29% and maximum pipe crown displacement by up to 39.5%. In addition, the EPS block density can reduce the maximum pipe crown displacement substantially.
Weeping in the Face of Fortune: Eco-Alienation in the Niger-Delta Ecopoetics
Authors: Abba Abba A. , Onyemachi Nkiru D.
Published: June 2020

Scholarship on Niger Delta ecopoetry has concentrated on the economic, socio-political and cultural implications of eco-degradation in the oil-rich Niger Delta region of the South-South in Nigeria, but falls short of addressing the trope of eco-alienation, the sense of separation between people and nature, which seems to be a significant idea in Niger Delta ecopoetics. For sure, literary studies in particular and the Humanities at large have shown considerable interest in the concept of the Anthropocene and the resultant eco-alienation which has dominated contemporary global ecopoetics since the 18th century. In the age of the Anthropocene, human beings deploy their exceptional capabilities to alter nature and its essence, including the ecosystem, which invariably leads to eco-alienation, a sense of breach in the relationship between people and nature. For the Humanities, if this Anthropocentric positioning of humans has brought socio-economic advancement to humans, it has equally eroded human values. This paper thus attempts to show that the anthropocentric positioning of humans at the center of the universe, with its resultant hyper-capitalist greed, is the premise in the discussion of eco-alienation in Tanure Ojaide’s Delta Blues and Home Songs (1998) and Nnimmo Bassey’s We Thought It Was Oil but It Was Blood (2002). Arguing that both poetry collections articulate the feeling of disconnect between the inhabitants of the Niger Delta region and the oil wealth in their community, the paper strives to demonstrate that the Niger Delta indigenes, as a result, have been compelled to perceive the oil environment no longer as a source of improved life but as a metaphor for death. Relying on ecocritical discursive strategies, and seeking to further foreground the implication of the Anthropocene in the conception of eco-alienation, the paper demonstrates how poetry, as a humanistic discipline, lives up to its promise as a powerful medium for interrogating the trope of eco-estrangement both in contemporary Niger Delta ecopoetry and in global eco-discourse.
GeohashTile: Vector Geographic Data Display Method Based on Geohash
Authors: Zhou Chang , Lu Huimei , Xiang Yong , Wu Jingbang , Wang Feng
Published: June 2020

In the development of geographic information-based applications for mobile devices, achieving better access speed and visual effects is the main research aim. In this paper, we propose a new geographic data display method based on Geohash, namely GeohashTile, to improve the performance of traditional geographic data display methods in data indexing, data compression, and the projection of different granularities. First, we use the Geohash encoding system to represent coordinates, as well as to partition and index large-scale geographic data. The data compression and tile encoding is accomplished by Geohash. Second, to realize a direct conversion between Geohash and screen-pixel coordinates, we adopt the relative position projection method. Finally, we improve the calculation and rendering efficiency by using the intermediate result caching method. To evaluate the GeohashTile method, we have implemented the client and the server of the GeohashTile system, which is also evaluated in a real-world environment. The results show that Geohash encoding can accurately represent latitude and longitude coordinates in vector maps, while the GeohashTile framework has obvious advantages when requesting data volume and average load time compared to the state-of-the-art GeoTile system.
A Gamification-Based Approach on Indoor Wayfinding Research
Authors: De Leeuw Dries , De Maeyer Philippe , De Cock Laure
Published: June 2020

Indoor environments can be very complex. Due to the challenges in these environments in combination with the absence of mobile wayfinding aids, a great need exists for innovative research on indoor wayfinding. In this explorative study, a game was developed in Unity to investigate whether the concept of gamification could be used in studies on indoor wayfinding so as to provide useful information regarding the link between wayfinding performance, personal characteristics, and building layout. Results show a significant difference between gamers and non-gamers as the complexity of the player movement has an important impact on the navigation velocity in the game. However, further analysis reveals that the architectural layout also has an impact on the navigation velocity and that wrong turns in the game are influenced by the landmarks at the decision points: navigating at deeper decision points in convex spaces is slower and landmarks of the categories pictograms and infrastructural were more effective in this particular building. Therefore, this explorative study, which provides an approach for the use of gamification in indoor wayfinding research, has shown that serious games could be successfully used as a medium for data acquisition related to indoor wayfinding in a virtual environment.
Natural Medicines and Their Underlying Mechanisms of Prevention and Recovery from Amyloid Β-Induced Axonal Degeneration in Alzheimer’s Disease
Authors: Kuboyama Tomoharu , Yang Ximeng , Tohda Chihiro
Published: June 2020

In Alzheimer’s disease (AD), amyloid β (Aβ) induces axonal degeneration, neuronal network disruption, and memory impairment. Although many candidate drugs to reduce Aβ have been clinically investigated, they failed to recover the memory function in AD patients. Reportedly, Aβ deposition occurred before the onset of AD. Once neuronal networks were disrupted by Aβ, they could hardly be recovered. Therefore, we speculated that only removal of Aβ was not enough for AD therapy, and prevention and recovery from neuronal network disruption were also needed. This review describes the challenges related to the condition of axons for AD therapy. We established novel in vitro models of Aβ-induced axonal degeneration. Using these models, we found that several traditional medicines and their constituents prevented or helped recover from Aβ-induced axonal degeneration. These drugs also prevented or helped recover from memory impairment in in vivo models of AD. One of these drugs ameliorated memory decline in AD patients in a clinical study. These results indicate that prevention and recovery from axonal degeneration are possible strategies for AD therapy.
Sleep Duration, Lipid Profile and Insulin Resistance: Potential Role of Lipoprotein(a)
Authors: Korostovtseva Lyudmila , Alieva Asiiat , Rotar Oxana , Bochkarev Mikhail , Boyarinova Maria , Sviryaev Yurii , Konradi Aleksandra , Shlyakhto Eugene
Published: June 2020

Lipoprotein (a) (Lp(a)) is considered a genetic factor for cardiovascular disease playing an important role in atherogenesis and thrombosis, but the evidence about its association with sleep duration is controversial. We evaluated the relation between self-reported sleep duration and Lp(a). Among 1600 participants of the population-based sample, we selected 1427 subjects without previously known cardiovascular events, who answered the questions about their sleep duration; had valid lipid profile results (total cholesterol, low- and high-density lipoproteins, Lp(a), apolipoprotein AI (ApoAI), ApoB, and ApoB/ApoAI); and did not take lipid-lowering drugs (mean age 46 ± 12 years). We performed a structured interview, which included questions about lifestyle, medical history, complaints, and sleep duration (How long have you been sleeping per night during the last month?). Sleep duration was classified as follows: <6 h/night—short, 6–9 h/night—normal, and ≥10 h/night—long. Overall, 73 respondents (5.2%) were short-sleepers and 69 (4.8%) long-sleepers. Males were slightly more prevalent among short-sleepers. The groups matched by age, body mass index, blood pressure, diabetes mellitus, and hypertension rate. Short-sleepers had lower rates of high total cholesterol (≥5.0 mmol/L), lower Lp(a) levels and lower rates of increased Lp(a) ≥0.5 g/L, and higher insulin and insulin resistance (assessed by the homeostatic model assessment for insulin resistance (HOMA-IR)). ApoAI, ApoB, their ratio, and other lab tests were similar in the groups. The multinomial logistic regression demonstrated that only the short sleep duration was independently (odds ratio (OR) 0.29, 95% confidence interval (CI) (0.09–0.91), p = 0.033) associated with Lp(a) (χ2 = 41.58, p = 0.003). Other influencing factors were smoking and HOMA-IR. Such an association was not found for long-sleepers. In conclusion, a short-sleep duration is associated with Lp(a). The latter might mediate the higher insulin resistance and higher cardiometabolic risks in short-sleepers.
Methodological Approach towards Evaluating the Effects of Non-Driving Related Tasks during Partially Automated Driving
Authors: Hollander Cornelia , Rauh Nadine , Naujoks Frederik , Hergeth Sebastian , Krems Josef F. , Keinath Andreas
Published: June 2020

Partially automated driving (PAD, Society of Automotive Engineers (SAE) level 2) features provide steering and brake/acceleration support, while the driver must constantly supervise the support feature and intervene if needed to maintain safety. PAD could potentially increase comfort, road safety, and traffic efficiency. As during manual driving, users might engage in non-driving related tasks (NDRTs). However, studies systematically examining NDRT execution during PAD are rare and most importantly, no established methodologies to systematically evaluate driver distraction during PAD currently exist. The current project’s goal was to take the initial steps towards developing a test protocol for systematically evaluating NDRT’s effects during PAD. The methodologies used for manual driving were extended to PAD. Two generic take-over situations addressing system limits of a given PAD regarding longitudinal and lateral control were implemented to evaluate drivers’ supervisory and take-over capabilities while engaging in different NDRTs (e.g., manual radio tuning task). The test protocol was evaluated and refined across the three studies (two simulator and one test track). The results indicate that the methodology could sensitively detect differences between the NDRTs’ influences on drivers’ take-over and especially supervisory capabilities. Recommendations were formulated regarding the test protocol’s use in future studies examining the effects of NDRTs during PAD.
Systemic Manifestations and Complications in Patients with Rheumatoid Arthritis
Authors: Kim Ji-Won , Suh Chang-Hee
Published: June 2020

Rheumatoid arthritis (RA) is a systemic autoimmune disease with symmetrical peripheral polyarthritis, predominantly involving the small joints [...]
Does the Use of the “Proseek® Multiplex Oncology I Panel” on Peritoneal Fluid Allow a Better Insight in the Pathophysiology of Endometriosis, and in Particular Deep-Infiltrating Endometriosis?
Authors: Perricos Alexandra , Wenzl René , Husslein Heinrich , Eiwegger Thomas , Gstoettner Manuela , Weinhaeusel Andreas , Beikircher Gabriel , Kuessel Lorenz
Published: June 2020

Endometriosis appears to share certain cancer-related processes, such as cell attachment, invasion, proliferation and neovascularization, some of which can also be found in other healthy tissues. In order to better understand the altered milieu of the peritoneal cavity, while acknowledging the reported similarities between endometriosis and neoplastic processes, we applied a multiplex oncology panel to search for specific biomarker signatures in the peritoneal fluid of women with endometriosis, women with deep-infiltrating endometriosis (DIE), as well as controls. In total, 84 patients were included in our study, 53 women with endometriosis and 31 controls. Ninety-two proteins were measured in prospectively collected peritoneal fluid (PF) samples, using the “Proseek® Multiplex Oncology I Panel”. We first compared patients with endometriosis versus controls, and in a second step, DIE versus endometriosis patients without DIE. Out of the 92 analyzed proteins, few showed significant differences between the groups. In patients with endometriosis, ICOS ligand, Endothelial growth factor, E-selectin, Receptor tyrosine-protein kinase erbB-2, Interleukin-6 receptor alpha, Vascular endothelial growth factor receptor 2, Fms-related tyrosine kinase 3 ligand, C-X-C motif chemokine 10, Epididymal secretory protein E4 and Folate receptor-alpha were decreased, while Interleukin-6 and Interleukin-8 were increased compared to controls. Looking at patients with DIE, we found Chemokine ligand 19, Stem cell factor, Vascular endothelial growth factor D, Interleukin-6 receptor alpha and Melanoma inhibitory activity to be increased compared to endometriosis patients without DIE. We have shown a distinct regulation of the immune response, angiogenesis, cell proliferation, cell adhesion and inhibition of apoptosis in PF of patients with endometriosis compared to controls. The specific protein pattern in the PF of DIE patients provides new evidence that DIE represents a unique entity of extrauterine endometriosis with enhanced angiogenetic and pro-proliferative features.
Validation of IOTA-ADNEX Model in Discriminating Characteristics of Adnexal Masses: A Comparison with Subjective Assessment
Authors: Jeong Soo Young , Park Byung Kwan , Lee Yoo Young , Kim Tae-Joong
Published: June 2020

(1) Background: The aim of this study is to compare the IOTA-ADNEX (international ovarian tumor analysis–assessment of different neoplasias in the adnexa) model with gynecologic experts in differentiating ovarian diseases. (2) Methods: All participants in this prospective study underwent ultrasonography (US) equipped with the IOTA-ADNEXTM model and subjective assessment by a sonographic expert. Receiver operating characteristic (ROC) curves were also generated to compare overall accuracies. The optimal cut-off value of the ADNEX model for excluding benign diseases was calculated. (3) Results: Fifty-nine participants were eligible: 54 and 5 underwent surgery and follow-up computed tomography (CT), respectively. Benign and malignant diseases were confirmed in 49 (83.1%) and 10 (16.9%) participants, respectively. The specificity of the ADNEX model was 0.816 (95% confidence interval (CI): 0.680–0.912) in all participants and 0.795 (95% CI, 0.647–0.902) in the surgical group. The area under the ROC curve of the ADNEX model (0.924) was not significantly different from that of subjective assessment (0.953 in all participants, 0.951 in the surgical group; p = 0.391 in all participants, p = 0.407 in the surgical group). The optimal cut-off point using the ADNEX model was 47.3%, with a specificity of 0.977 (95% CI: 0.880–0.999). (4) Conclusions: The IOTA-ADNEX model is equal to gynecologic US experts in excluding benign ovarian tumors. Subsequently, being familiar with this US software may help gynecologic beginners to reduce unnecessary surgery.
Clinical and Psychological Impact of COVID-19 Infection in Adult Patients with Eosinophilic Gastrointestinal Disorders during the SARS-CoV-2 Outbreak
Authors: Savarino Edoardo Vincenzo , Iovino Paola , Santonicola Antonella , Ghisa Matteo , Laserra Giorgio , Barberio Brigida , Maniero Daria , Lorenzon Greta , Ciacci Carolina , Savarino Vincenzo , Zingone Fabiana
Published: June 2020

Eosinophilic gastrointestinal diseases (EGIDs) are chronic gastrointestinal conditions requiring corticosteroid and immunosuppressive therapy for disease control. Patients with EGIDs usually report impaired quality of life. We aimed to report the clinical and psychological impact of COVID-19 infection in EGID patients. In this prospective web-based study we invited all consecutive EGID patients attending the University Hospital of Salerno (Campania) and Padua (Veneto) to fill an ad hoc COVID-19 survey. Moreover, a telemedicine service for direct consultation was organized. Data regarding the occurrence and perception of COVID-19 infection as well as clinical information were recorded. The study population included 102 EGID patients (mean age 36.6 years, 34 females), of whom 89 had eosinophilic esophagitis, nine had gastroenteritis, and four had colitis. No patient was diagnosed with COVID-19 or had recurrence of his/her primary disease. All of them were adherent to therapy and preventive measures adoption. Most patients were worried because of COVID-19 and social preventing measures but did not consider themselves at major risk or susceptible to COVID-19 or other infections due to their chronic condition or therapy. Female gender and low education level were associated to a higher psychological perception of COVID-19 compared to lockdown status or other demographic and clinical factors (p < 0.05). Overall, COVID-19 had a limited clinical impact on patients with EGIDs. The degree of education and sex, but not the fact of living in a lockdown area, influenced the perception of SARS-CoV-2 infection.
Association of Lower Plasma Homoarginine Concentrations with Greater Risk of All-Cause Mortality in the Community: The Framingham Offspring Study
Authors: Schwedhelm Edzard , Song Rebecca J. , Vasan Ramachandran S. , van den Heuvel Edwin R. , Hannemann Juliane , Xanthakis Vanessa , Böger Rainer
Published: June 2020

Lower circulating homoarginine concentrations have been associated with morbidity and mortality in patients with established cardiovascular disease (CVD). We assayed plasma homoarginine concentrations in 3331 Framingham Offspring Study participants attending examination cycle six (mean age 58.6 years, 53% women). We evaluated correlates of plasma homoarginine and related homoarginine to incident CVD and death. We also classified participants as having higher (upper quartile) versus lower (lower three quartiles) homoarginine and previously assayed asymmetric dimethylarginine (ADMA) concentrations, and created cross-classification groups. We observed 630 incident CVD events and 940 deaths during a median follow-up of 18 years. In multivariable regression analysis, homoarginine was associated positively with male sex, body mass index, anti-hypertensive medication use and systolic blood pressure, but inversely with age and smoking. Higher homoarginine levels were associated with a lower mortality risk (hazard ratio (HR) per SD increment, 0.83, 95% CI: 0.74–0.93) adjusting for standard CVD risk factors, and ADMA. Among the cross-classification groups, participants with higher homoarginine and lower ADMA had a lower mortality risk (HR, 0.81, 95% CI: 0.67–0.98) compared to those with low levels of both. Further studies are needed to dissect the mechanisms of the association of homoarginine and mortality over decades in the community.
Delayed Thrombin Generation Is Associated with Minor Bleedings in Venous Thromboembolism Patients on Rivaroxaban: Usefulness of Calibrated Automated Thrombography
Authors: Zalewski Jaroslaw , Stepien Konrad , Nowak Karol , Caus Sandi , Butenas Saulius , Undas Anetta
Published: June 2020

Bleeding is the most feared and difficult to predict adverse event of anticoagulation. We sought to investigate whether calibrated automated thrombography (CAT) parameters are associated with minor bleeding (MB) in anticoagulated patients following venous thromboembolism (VTE). Enrolled were 132 patients on rivaroxaban, 145 on vitamin K antagonists (VKA) and 31 controls who stopped anticoagulation. Prior to the next dose of the anticoagulant, we measured CAT parameters, along with rivaroxaban concentration and INR. During a median follow-up of 10 months, we recorded minor and major bleedings. On rivaroxaban, 27 (20.5%) patients with MB had longer time to start thrombin generation, lower peak thrombin generation and lower endogenous thrombin potential compared with subjects without MB (all p < 0.001). All CAT parameters, except for peak thrombin generation (p = 0.049), were similar in VKA patients with (n = 25, 17.2%) vs. without MBs. By logistic regression, time to start thrombin generation (p = 0.007) and unprovoked VTE (p = 0.041) independently predicted MBs on rivaroxaban. Major bleedings were more frequent in patients with MBs (17.3% vs. 1.8%, p < 0.001). Abnormal CAT parameters characterize VTE patients prone to MBs on rivaroxaban, but not on VKA. Time to start thrombin generation measured about 24 h since the last rivaroxaban dose might help predict MBs.
Reduction of High Expressed Emotion and Treatment Outcomes in Anorexia Nervosa—Caregivers’ and Adolescents’ Perspective
Authors: Philipp Julia , Truttmann Stefanie , Zeiler Michael , Franta Claudia , Wittek Tanja , Schöfbeck Gabriele , Mitterer Michaela , Mairhofer Dunja , Zanko Annika , Imgart Hartmut , Auer-Welsbach Ellen , Treasure Janet , Wagner Gudrun , Karwautz Andreas F. K.
Published: June 2020

High expressed emotion (EE) is common in caregivers of patients with anorexia nervosa (AN) and associated with poorer outcome for patients. In this study, we examined the prevalence of high EE in caregivers of adolescents with AN and analyzed predictors for EE using multivariate linear regression models. We further analyzed whether EE is reduced by the “Supporting Carers of Children and Adolescents with Eating Disorders in Austria” (SUCCEAT) intervention using general linear mixed models and whether a reduction of EE predicts patients’ outcomes. Caregivers were randomly allocated to the SUCCEAT workshop (N = 50) or online intervention (N = 50) and compared to a comparison group (N = 49). EE and patients’ outcomes were assessed at the baseline, post-intervention, and at the 12-month follow-up. Up to 47% of caregivers showed high EE. Lower caregiver skills, higher AN symptom impact, higher levels of depression and motivation to change in caregivers were significant predictors for high EE. EE significantly decreased in the SUCCEAT groups and the comparison group according to the caregivers’, but not the patients’ perspective. The level of reduction could partially predict subjective improvement and improvement in clinically assessed AN symptoms and body mass index of patients. Implementing interventions for caregivers addressing EE in the treatment of adolescents with AN is strongly recommended.
High Incidence of Amoxicillin-Induced Crystal Nephropathy in Patients Receiving High Dose of Intravenous Amoxicillin
Authors: Garnier Anne-Sophie , Dellamaggiore Juliette , Brilland Benoit , Lagarce Laurence , Abgueguen Pierre , Furber Alain , Legrand Erick , Subra Jean-François , Drablier Guillaume , Augusto Jean-François
Published: June 2020

Background: Amoxicillin (AMX)-induced crystal nephropathy (AICN) is considered as a rare complication of high dose intravenous (IV) AMX administration. However, recently, its incidence seems to be increasing based on French pharmacovigilance centers. Occurrence of AICN has been observed mainly with IV administration of AMX and mostly under doses over 8 g/day. Given that pharmacovigilance data are based on declaration, the real incidence of AICN may be underestimated. Thus, the primary objective of the present study was to determine the incidence of AICN in the current practice. Materials and Methods: We conducted a retrospective study between 1 January 2015 and 31 December 2017 in Angers University Hospital. Inclusion criteria were age over 18 years-old and IV AMX administration of at least 8 g/day for more than 24 h. Patients admitted directly into the intensive care units were excluded. Medical records of patients that developed Kidney Disease:Improving Global Outcome (KDIGO) stage 2–3 acute kidney injury (AKI) were reviewed by a nephrologist and a specialist in pharmacovigilance. AICN was retained if temporality analysis was conclusive, after exclusion of other causes of AKI, in absence of other nephrotoxic drug administration. Results: A total of 1303 patients received IV AMX for at least 24 h. Among them, 358 (27.5%) were exposed to AMX doses of at least 8 g/day and were included. Patients were predominantly males (68.2%) with a mean age of 69.1 years-old. AMX was administered for a medical reason in 78.5% of cases. Patients received a median dose of AMX of 12 g/day (152.0 mg/kg/day). Seventy-three patients (20.4%) developed AKI, 42 (56.8%) of which were KDIGO stage 2 or 3. Among the latter, AICN diagnosis was retained in 16 (38.1%) patients, representing an incidence of 4.47% of total patients exposed to high IV AMX doses. Only female gender was associated with an increased risk of AICN. AMX dose was not significantly associated with AICN development. Conclusion: This study suggests a high incidence of AICN in patients receiving high IV AMX doses, representing one third of AKI causes in our study. Female gender appeared as the sole risk factor for AICN in this study.