bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk of Hospitalization Associated with Cardiovascular Medications in the Elderly Italian Population: A Nationwide Multicenter Study in Emergency Departments
Authors: Crescioli Giada , Bettiol Alessandra , Bonaiuti Roberto , Tuccori Marco , Rossi Marco , Capuano Annalisa , Pagani Silvia , Spada Giulia , Venegoni Mauro , Vighi Giuseppe Danilo , Mannaioni Guido , Vannacci Alfredo , Lombardi Niccolò ,   MEREAFaPS Study group
Published: January 2021

Background: There is a significant gap in knowledge addressing cardiovascular (CV) medications safety in elderly. In this context, our purposes were to define clinical and pharmacological characteristics of outpatients’ adverse drug events (ADEs) related to CV medications leading to emergency department (ED) visits in the elderly Italian patients according to different age groups, and to evaluate the risk of hospitalization associated to ADEs in this population.

Methods: A multicentre, retrospective study was performed on reports of suspected ADEs collected between 2007–2018 in 94 EDs involved in the MEREAFaPS Study. Elderly patients who experienced one or more CV medications-related ADEs leading to ED visit were selected. Patients’ characteristics, suspected (ATC classes B and C) and concomitant drugs, and ADE description were collected. Elderly patients were stratified into three age groups (65–74, 75–84, and ≥85 years) and compared to adults (18–64 years). Logistic regression analyses were used to estimate the reporting odds ratios (RORs) with 95% confidence intervals (CIs) of ADE-related hospitalization adjusting for sex, presence of two or more suspected drugs, concomitant drugs, and one or more comorbidities.

Results: Among elderly, 16,926 reports of suspected ADE related to CV medications were collected, and 6,694 (39.5%) resulted in hospitalization. Patients were mostly female, Caucasians, and middle-old (75–84). 78.9% of patients were treated with only one suspected drug, and 71.9% and 47.1% reported concomitant medications and comorbidities, respectively. Compared to adults, risk of hospitalization was significantly higher for middle-old and oldest-old patients exposed to vitamin K antagonists (1.29 [1.09–1.52] and 1.56 [1.30–187]), direct thrombin inhibitors (3.41 [1.44–8.08] and 4.12 [1.67–10.17]), antiplatelets (1.51 [1.26–1.81] and 2.09 [1.71–2.57]), and beta-blockers (1.89 [1.38–2.59 and 2.31 [1.60–3.35]). Overall, a higher risk of hospitalization was observed for renin-angiotensin system inhibitors (1.32 [1.04–1.68], 1.65 [1.32–2.06], and 2.20 [1.70–2.85]), presence of two or more concomitant drugs, and concomitant conditions.

Conclusion: Our real-world findings underline relevant safety aspects of CV medications in the elderly Italian population. ED clinicians must always consider the higher risk of hospitalization related to the use of CV drugs in elderly, particularly in oldest-old ones, for antiarrhythmics, beta-blocking agents, renin-angiotensin system inhibitors, antiplatelets, and anticoagulants.
HIF Prolyl Hydroxylase Inhibitors for COVID-19 Treatment: Pros and Cons
Authors: Poloznikov Andrey A. , Nersisyan Stepan A. , Hushpulian Dmitry M. , Kazakov Eliot H. , Tonevitsky Alexander G. , Kazakov Sergey V. , Vechorko Valery I. , Nikulin Sergey V. , Makarova Julia A. , Gazaryan Irina G.
Published: January 2021

The review analyzes the potential advantages and problems associated with using HIF prolyl hydroxylase inhibitors as a treatment for COVID-19. HIF prolyl hydroxylase inhibitors are known to boost endogenous erythropoietin (Epo) and activate erythropoiesis by stabilizing and activating the hypoxia inducible factor (HIF). Recombinant Epo treatment has anti-inflammatory and healing properties, and thus, very likely, will be beneficial for moderate to severe cases of COVID-19. However, HIF PHD inhibition may have a significantly broader effect, in addition to stimulating the endogenous Epo production. The analysis of HIF target genes reveals that some HIF-targets, such as furin, could play a negative role with respect to viral entry. On the other hand, HIF prolyl hydroxylase inhibitors counteract ferroptosis, the process recently implicated in vessel damage during the later stages of COVID-19. Therefore, HIF prolyl hydroxylase inhibitors may serve as a promising treatment of COVID-19 complications, but they are unlikely to aid in the prevention of the initial stages of infection.
Tangshen Formula Attenuates Diabetic Kidney Injury by Imparting Anti-pyroptotic Effects via the TXNIP-NLRP3-GSDMD Axis
Authors: Li Nan , Zhao Tingting , Cao Yongtong , Zhang Haojun , Peng Liang , Wang Yan , Zhou Xuefeng , Wang Qian , Li Jialin , Yan Meihua , Dong Xi , Zhao Hailing , Li Ping
Published: January 2021

We previously reported that Tangshen formula (TSF), a Chinese herbal medicine for diabetic kidney disease (DKD) therapy, imparts renal protective effects. However, the underlying mechanisms of these effects remain unclear. Pyroptosis is a form of programmed cell death that can be triggered by the NLRP3 inflammasome. Recently, the association between the pyroptosis of renal resident cells and DKD was established, but with limited evidence. This study aimed to investigate whether the renal protective effects of TSF are related to its anti-pyroptotic effect. DKD rats established by right uninephrectomy plus a single intraperitoneal injection of STZ and HK-2 cells stimulated by AGEs were used. In vivo, TSF reduced the 24 h urine protein (24 h UP) of DKD rats and alleviated renal pathological changes. Meanwhile, the increased expression of pyroptotic executor (GSDMD) and NLRP3 inflammasome pathway molecules (NLRP3, caspase-1, and IL-1β) located in the tubules of DKD rats were downregulated with TSF treatment. In vitro, we confirmed the existence of pyroptosis in AGE-stimulated HK-2 cells and the activation of the NLRP3 inflammasome. TSF reduced pyroptosis and NLRP3 inflammasome activation in a dosage-dependent manner. Then, we used nigericin to determine that TSF imparts anti-pyroptotic effects by inhibiting the NLRP3 inflammasome. Finally, we found that TSF reduces reactive oxygen species (ROS) production and thioredoxin-interacting protein (TXNIP) expression in AGE-stimulated HK-2 cells. More importantly, TSF decreased the colocalization of TXNIP and NLRP3, indicating that ROS-TXNIP may be the target of TSF. In summary, the anti-pyroptotic effect via the TXNIP-NLRP3-GSDMD axis may be an important mechanism of TSF for DKD therapy.
Metformin: A Novel Weapon Against Inflammation
Authors: Bai Bo , Chen Haibo
Published: January 2021

It has become widely accepted that inflammation is a driving force behind a variety of chronic diseases, such as cardiovascular disease, diabetes, kidney disease, cancer, neurodegenerative disorders, etc. However, the existing nonsteroidal anti-inflammatory drugs show a limited utility in clinical patients. Therefore, the novel agents with different inflammation-inhibitory mechanisms are worth pursuing. Metformin, a synthetic derivative of guanidine, has a history of more than 50 years of clinical experience in treating patients with type 2 diabetes. Intense research efforts have been dedicated to proving metformin’s inflammation-inhibitory effects in cells, animal models, patient records, and randomized clinical trials. The emerging evidence also indicates its therapeutic potential in clinical domains other than type 2 diabetes. Herein, this article appraises current pre-clinical and clinical findings, emphasizing metformin’s anti-inflammatory properties under individual pathophysiological scenarios. In summary, the anti-inflammatory effects of metformin are evident in pre-clinical models. By comparison, there are still clinical perplexities to be addressed in repurposing metformin to inflammation-driven chronic diseases. Future randomized controlled trials, incorporating better stratification/targeting, would establish metformin’s utility in this clinical setting.
Exploring the New Horizon of AdipoQ in Obesity-Related Alzheimer’s Dementia
Authors: Uddin Md. Sahab , Rahman Md. Motiar , Sufian Mohammad Abu , Jeandet Philippe , Ashraf Ghulam Md. , Bin-Jumah May N. , Mousa Shaker A. , Abdel-Daim Mohamed M. , Akhtar Muhammad Furqan , Saleem Ammara , Amran Md. Shah
Published: January 2021

Alzheimer’s disease (AD) is the most common form of dementia, which causes abnormalities in learning, thinking, memory, as well as behavior. Generally, symptoms of AD develop gradually and aggravate over time, and consequently severely interfere with daily activities. Furthermore, obesity is one of the common risk factors for dementia. Dysregulation of adipokine and adipocyte dysfunction are assumed to be accountable for the high risk of obesity in people that develop many related disorders such as AD. Moreover, it has been observed that the dysfunction of adipose is connected with changes in brain metabolism, brain atrophy, cognitive decline, impaired mood, neuroinflammation, impaired insulin signaling, and neuronal dysfunction in people with obesity. Conversely, the pathological mechanisms, as well as the molecular players which are involved in this association, have been unclear until now. In this article, we discuss the impact of adiponectin (AdipoQ) on obesity-related Alzheimer’s dementia.
New Actors and Democratic Governance in a Rising Africa
Authors: Ahere John Rabuogi
Published: January 2021

This paper broadly examines the continued nuancing of the practice of democracy in Africa with a focus on how Africa’s democratic governance is increasingly getting influenced by new actors in the international system, who are driving the formation of a new world order that challenges the current unipolar liberal global order. The paper traces the origins and rationale of the democratization project in Africa and uses this as a basis to delve into some issues around which many African countries have increasingly been engaging with new actors. These broad aspects include: Africa’s international relations, peace and security; civil liberties as well as investments and trade. This paper contends that some states in Africa are charting middle grounds that increasingly, specifically align with their national/elite interests, and broadly, is in tune with the consolidating discourse on Africa Rising.
Comparison of Human Social Brain Activity During Eye-Contact With Another Human and a Humanoid Robot
Authors: Kelley Megan S. , Noah J. Adam , Zhang Xian , Scassellati Brian , Hirsch Joy
Published: January 2021

Robot design to simulate interpersonal social interaction is an active area of research with applications in therapy and companionship. Neural responses to eye-to-eye contact in humans have recently been employed to determine the neural systems that are active during social interactions. Whether eye-contact with a social robot engages the same neural system remains to be seen. Here, we employ a similar approach to compare human-human and human-robot social interactions. We assume that if human-human and human-robot eye-contact elicit similar neural activity in the human, then the perceptual and cognitive processing is also the same for human and robot. That is, the robot is processed similar to the human. However, if neural effects are different, then perceptual and cognitive processing is assumed to be different. In this study neural activity was compared for human-to-human and human-to-robot conditions using near infrared spectroscopy for neural imaging, and a robot (Maki) with eyes that blink and move right and left. Eye-contact was confirmed by eye-tracking for both conditions. Increased neural activity was observed in human social systems including the right temporal parietal junction and the dorsolateral prefrontal cortex during human-human eye contact but not human-robot eye-contact. This suggests that the type of human-robot eye-contact used here is not sufficient to engage the right temporoparietal junction in the human. This study establishes a foundation for future research into human-robot eye-contact to determine how elements of robot design and behavior impact human social processing within this type of interaction and may offer a method for capturing difficult to quantify components of human-robot interaction, such as social engagement.
The Equipment Used in the SF6 Technique to Estimate Methane Emissions Has No Major Effect on Dairy Cow Behavior
Authors: Pereira Fabiellen Cristina , Teixeira Dayane Lemos , Boyle Laura Ann , Pinheiro Machado Filho Luiz Carlos , Williams Shaun Richard Owen , Enriquez-Hidalgo Daniel
Published: January 2021

The natural behavior of animals can be disrupted by the techniques and materials of research methodologies. This study aimed to evaluate the effect of the equipment used in the SF6 tracer technique to estimate enteric methane emissions on the behavior of lactating dairy cows. The cows (n = 24) were allocated to one of two diets: CONTROL and experimental diet (MIX). Behavior was assessed through video recordings between milking times during four phases: 3 days before fitting the cows with the SF6 equipment (PRE), first 2 days after the cows were fitted with the SF6 equipment (ADAP), 3 days during methane emission measurements (MEAS), and 2 days after the SF6 equipment removal (POST). The behaviors recorded included eating, ruminating or idling, resting, and others. Affiliative or agonistic and discomfort behaviors (scratching or pushing the equipment) were also recorded. Lying time was recorded over 14 days using dataloggers fitted to the cows' leg. Milk production and feed intake were recorded daily. MIX cows ruminated more than CONTROL cows (P = 0.05). The cows ruminated more at MEAS than in any other phase (P < 0.01). Time spent idling gradually decreased from PRE to MEAS for MIX cows (P < 0.01). The cows were lying down longer in MEAS than in ADAP and POST (P < 0.01). The time spent lying with the head down was shorter during PRE and ADAP than during POST (P < 0.05). No difference was observed in the occurrence of discomfort or agonistic behaviors (P > 0.05). Affiliative behaviors occurred more often in ADAP than in MEAS (P < 0.05). There was no difference between phases in daily lying time, number of lying bouts per day, or mean bout duration (P > 0.05). Milk production was not influenced by the SF6 equipment (P > 0.05). Dry matter intake was higher for CONTROL cows (P < 0.01), and it decreased from PRE to MEAS (P < 0.01). However, milk yield did not differ between cows wearing the SF6 equipment and those without it (P > 0.05). We conclude that the SF6 equipment had a minimal effect on dairy cow behavior.
Effects of a Plasma Water and Biostimulant on Lawn Functional Value
Authors: Talar-Krasa Marta , Wolski Karol , Radkowski Adam , Khachatryan Karen , Bujak Henryk , Bocianowski Jan
Published: January 2021

The research was conducted between 2014 and 2016 at the Agricultural Experimental Station of the University of Environmental and Life Sciences in Wrocław. In the experiment, Poa pratensis and Lolium perenne in pure stand and in mixtures were used as Factor A. Two substances that stimulate grass growth and development constituted Factor B. The first was a biostimulant produced from brown algae (Phaeophyceae), containing various essential chemical compounds including amino acids, vitamins, alginic acid, microelements, and other unexplored biologically active components. The other was water treated with low-pressure glow plasma (LPGP). The seeds were sown in well-mixed light, alluvial loamy sand soil. During three growing seasons, a 9-point scale was used to evaluate grass density, leaf fineness, susceptibility to disease, and lawn overwintering. The lawns were mown every 14 days at a height of 4 cm. The substances with a stimulating effect significantly affected lawn grass features, including turf density and overwintering. Additionally, the biostimulant and plasma water reduced the incidence of fungal diseases. Better transport of water in plants after its low-pressure glow plasma treatment may be due to the effect of its declustered structure, its higher oxygen concentration, and its better solubility of the biostimulant.
Is Palm Kernel Cake a Suitable Alternative Feed Ingredient for Poultry?
Authors: Azizi Mohammad Naeem , Loh Teck Chwen , Foo Hooi Ling , Teik Chung Eric Lim
Published: January 2021

Palm kernel cake (PKC), a by-product of oil extracted from palm nuts through expeller press or solvent extraction procedures is one of the highest quantities of locally available and potentially inexpensive agricultural product. PKC provides approximately 14–18% of crude protein (CP), 12–20% crude fiber (CF), 3–9% ether extract (EE), and different amounts of various minerals that feasible to be used as a partial substitute of soybean meal (SBM) and corn in poultry nutrition. Poultry’s digestibility is reported to be compromised due to the indigestion of the high fiber content, making PKC potentially low for poultry feeding. Nevertheless, solid-state fermentation (SSF) can be applied to improve the nutritional quality of PKC by improving the CP and reducing CF content. PKC also contains β-mannan polysaccharide, which works as a prebiotic. However, there is a wide variation for the inclusion level of PKC in the broiler diet. These variations may be due to the quality of PKC, its sources, processing methods and value-added treatment. It has been documented that 10–15% of treated PKC could be included in the broiler’s diets. The inclusion levels will not contribute to a negative impact on the growth performances and carcass yield. Furthermore, it will not compromise intestinal microflora, morphology, nutrient digestibility, and immune system. PKC with a proper SSF process (FPKC) can be offered up to 10–15% in the diets without affecting broilers’ production performance.
NADPH Oxidase 5 Induces Changes in the Unfolded Protein Response in Human Aortic Endothelial Cells and in Endothelial-Specific Knock-in Mice
Authors: Cortés Adriana , Pejenaute Álvaro , Marqués Javier , Izal Íñigo , Cenoz Silvia , Ansorena Eduardo , Martínez-Irujo Juan José , de Miguel Carlos , Zalba Guillermo
Published: January 2021

Oxidative stress constitutes a key molecular mechanism in the development of cardiovascular diseases. A potential relationship between reactive oxygen species (ROS) driven by the NADPH oxidase family (NOX) and the unfolded protein response (UPR) has been postulated. Nevertheless, there is a lack of information about the crosstalk between NOX5 homologue and the UPR in a cardiovascular context. The main aim was to analyze NOX5-mediated ROS effects in the UPR and its importance in cardiovascular diseases. To this effect, we used an adenoviral NOX5-β overexpression model in human aortic endothelial cells (HAEC) and a conditional endothelial NOX5 knock-in mouse. Using expression arrays, we investigated NOX5-induced genomic changes in HAEC. Compared with the control HAEC, 298 genes were differentially expressed. Gene ontology analysis revealed the activation of numerous cellular routes, the most relevant being the UPR pathway. Using real-time PCR and Western Blot experiments, we confirmed that NOX5 overexpression induced changes in the expression of the UPR components, which were associated with increased apoptosis. Moreover, in endothelial-specific NOX5 knock-in mice, we found changes in the expression of the UPR components genes. In these mice, myocardial infarction was performed by permanent coronary artery ligation; however, NOX5 expression was not associated with differences in the UPR components mRNA levels. In these animals, we found significant associations between the UPR components gene expression and echocardiographic parameters. Our data support the idea that NOX5-derived ROS may modulate the UPR pathway in endothelial cells, which might play a relevant role in cardiac physiology.
Impact of Mild Oven Cooking Treatments on Carotenoids and Tocopherols of Cheddar and Depurple Cauliflower (Brassica oleracea L. var. botrytis)
Authors: Nartea Ancuta , Fanesi Benedetta , Falcone Pasquale Massimiliano , Pacetti Deborah , Frega Natale Giuseppe , Lucci Paolo
Published: January 2021

The effect of steam and sous-vide oven procedures on liposoluble antioxidants of colored cauliflower (orange and purple) was assessed for the first time and compared with domestic practice (boiling). In raw samples, the total carotenoid content was 10-fold higher in Cheddar than in Depurple (20.9 ± 2.1 vs. 2.3 ± 0.5 mg/kg dry weight), whereas the level of tocopherols was similar (28.5 ± 4.4 vs. 33 ± 5.2 mg/kg dry weight). The Cheddar liposoluble antioxidant matter contained violaxanthin, neoxanthin, α-carotene and δ-tocopherol, not detected in Depurple. All tests increased the bioactive compounds extractability with steam oven and sous-vide displaying similar effects, lower than boiling. In boiled Cheddar cauliflower, the total carotenoids and tocopherols contents increased with cooking time until they were 13-fold and 6-fold more than in raw cauliflower, respectively. Conversely, in the Depurple variety, contents increased by half with respect to the orange variety. However, from a nutritional point of view, no differences were revealed among the three different cooking treatments in terms of vitamin A and E levels expressed in μg/100 g of fresh vegetable because of the higher water content of boiled samples that must be considered when evaluating the effect of thermal treatment on cauliflower nutritional traits.
The Pancreatic β-Cell: The Perfect Redox System
Authors: Ježek Petr , Holendová Blanka , Jabůrek Martin , Tauber Jan , Dlasková Andrea , Plecitá-Hlavatá Lydie
Published: January 2021

Pancreatic β-cell insulin secretion, which responds to various secretagogues and hormonal regulations, is reviewed here, emphasizing the fundamental redox signaling by NADPH oxidase 4- (NOX4-) mediated H2O2 production for glucose-stimulated insulin secretion (GSIS). There is a logical summation that integrates both metabolic plus redox homeostasis because the ATP-sensitive K+ channel (KATP) can only be closed when both ATP and H2O2 are elevated. Otherwise ATP would block KATP, while H2O2 would activate any of the redox-sensitive nonspecific calcium channels (NSCCs), such as TRPM2. Notably, a 100%-closed KATP ensemble is insufficient to reach the −50 mV threshold plasma membrane depolarization required for the activation of voltage-dependent Ca2+ channels. Open synergic NSCCs or Cl− channels have to act simultaneously to reach this threshold. The resulting intermittent cytosolic Ca2+-increases lead to the pulsatile exocytosis of insulin granule vesicles (IGVs). The incretin (e.g., GLP-1) amplification of GSIS stems from receptor signaling leading to activating the phosphorylation of TRPM channels and effects on other channels to intensify integral Ca2+-influx (fortified by endoplasmic reticulum Ca2+). ATP plus H2O2 are also required for branched-chain ketoacids (BCKAs); and partly for fatty acids (FAs) to secrete insulin, while BCKA or FA β-oxidation provide redox signaling from mitochondria, which proceeds by H2O2 diffusion or hypothetical SH relay via peroxiredoxin “redox kiss” to target proteins.
Fast and Low-Cost Synthesis of MoS2 Nanostructures on Paper Substrates for Near-Infrared Photodetectors
Authors: Cordeiro Neusmar J. A. , Gaspar Cristina , Oliveira Maria J. de , Nunes Daniela , Barquinha Pedro , Pereira Luís , Fortunato Elvira , Martins Rodrigo , Laureto Edson , Lourenço Sidney A.
Published: January 2021

Recent advances in the production and development of two-dimensional transition metal dichalcogenides (2D TMDs) allow applications of these materials, with a structure similar to that of graphene, in a series of devices as promising technologies for optoelectronic applications. In this work, molybdenum disulfide (MoS2) nanostructures were grown directly on paper substrates through a microwave-assisted hydrothermal synthesis. The synthesized samples were subjected to morphological, structural, and optical analysis, using techniques such as scanning electron microscopy (SEM), X-ray diffraction (XRD), and Raman. The variation of synthesis parameters, as temperature and synthesis time, allowed the manipulation of these nanostructures during the growth process, with alteration of the metallic (1T) and semiconductor (2H) phases. By using this synthesis method, two-dimensional MoS2 nanostructures were directly grown on paper substrates. The MoS2 nanostructures were used as the active layer, to produce low-cost near-infrared photodetectors. The set of results indicates that the interdigital MoS2 photodetector with the best characteristics (responsivity of 290 mA/W, detectivity of 1.8 × 109 Jones and external quantum efficiency of 37%) was obtained using photoactive MoS2 nanosheets synthesized at 200 °C for 120 min.
Enhancement of Subcooled Flow Boiling Heat Transfer with High Porosity Sintered Fiber Metal
Authors: Otomo Yusuke , Santiago Galicia Edgar , Enoki Koji
Published: January 2021

We conducted experimental research using high-porosity sintered fiber attached on the surface, as a passive method to increase the heat flux for subcooled flow boiling. Two different porous thicknesses (1 and 0.5 mm) and one bare surface (0 mm) were compared under three different inlet subcooling temperatures (30, 50 and 70 K) and low mass flux (150–600 kg·m−2·s−1) using deionized water as the working fluid under atmospheric pressure. The test section was a rectangular channel, and the hydraulic diameter was 10 mm. The results showed that the heat flux on porous surfaces with a thickness of 1 and 0.5 mm increased by 60% and 40%, respectively, compared to bare surfaces at ΔTsat = 40 K at a subcooled temperature of 50 K and mass flux of 300 kg·m−2·s−1. An abrupt increase in the wall superheat was avoided, and critical heat flux (CHF) was not reached on the porous surfaces. The flow pattern and bubble were recorded with a high-speed camera, and the bubble dynamics are discussed.
Optimal Coordination of Over-Current Relays in Microgrids Using Unsupervised Learning Techniques
Authors: Saldarriaga-Zuluaga Sergio D. , López-Lezama Jesús M. , Muñoz-Galeano Nicolás
Published: January 2021

Microgrids constitute complex systems that integrate distributed generation (DG) and feature different operational modes. The optimal coordination of directional over-current relays (DOCRs) in microgrids is a challenging task, especially if topology changes are taken into account. This paper proposes an adaptive protection approach that takes advantage of multiple setting groups that are available in commercial DOCRs to account for network topology changes in microgrids. Because the number of possible topologies is greater than the available setting groups, unsupervised learning techniques are explored to classify network topologies into a number of clusters that is equal to the number of setting groups. Subsequently, optimal settings are calculated for every topology cluster. Every setting is saved in the DOCRs as a different setting group that would be activated when a corresponding topology takes place. Several tests are performed on a benchmark IEC (International Electrotechnical Commission) microgrid, evidencing the applicability of the proposed approach.
Evaluation of Automated Segmentation Algorithm for Macular Volumetric Measurements of Eight Individual Retinal Layer Thickness
Authors: Zahavi Ori , Domínguez-Vicent Alberto , Brautaset Rune , Venkataraman Abinaya Priya
Published: January 2021

Background: We evaluated the performance of an automated algorithm available on a clinical OCT (Canon-HS100) for macular volumetric measurements of eight individual retinal layers. Methods and Analysis: Two consecutive three-dimensional scans were acquired on 29 subjects with healthy retinas. Thickness measurements were obtained from eight individual retinal layers in nine macular sectors based on Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. The repeatability was evaluated using the within-subject standard deviation from which the repeatability limits (Rlimit) and coefficient of variation (CoV) were calculated. Results: The repeatability metrics varied among different layers and sectors. The variation among the sectors was larger in two of the outer layers (plexiform and nuclear layer) and the retinal nerve fiber layer. For the other five layers, the repeatability limit was less than 5µm and CoV was less than 7.5% in all nine ETDRS sectors. Conclusions: The repeatability of the OCT-HS100 to measure eight individual retinal layers is good in general. Nevertheless, the repeatability is not homogeneous among different layers and sectors. This needs to be taken into account while designing clinical measurement protocols.
Downscaled Finite Element Modeling of Metal Targets for Surface Roughness Level under Pulsed Laser Irradiation
Authors: Kaselouris Evaggelos , Kosma Kyriaki , Orphanos Yannis , Skoulakis Alexandros , Fitilis Ioannis , Markopoulos Angelos P. , Bakarezos Makis , Tatarakis Michael , Papadogiannis Nektarios A. , Dimitriou Vasilis
Published: January 2021

A three-dimensional, thermal-structural finite element model, originally developed for the study of laser–solid interactions and the generation and propagation of surface acoustic waves in the macroscopic level, was downscaled for the investigation of the surface roughness influence on pulsed laser–solid interactions. The dimensions of the computational domain were reduced to include the laser-heated area of interest. The initially flat surface was progressively downscaled to model the spatial roughness profile characteristics with increasing geometrical accuracy. Since we focused on the plastic and melting regimes, where structural changes occur in the submicrometer scale, the proposed downscaling approach allowed for their accurate positioning. Additionally, the multiscale simulation results were discussed in relation to experimental findings based on white light interferometry. The combination of this multiscale modeling approach with the experimental methodology presented in this study provides a multilevel scientific tool for an in-depth analysis of the influence of heat parameters on the surface roughness of solid materials and can be further extended to various laser–solid interaction applications.
Zero-Dynamics Attack on Wind Turbines and Countermeasures Using Generalized Hold and Generalized Sampler
Authors: Kim Daehan , Ryu Kunhee , Back Juhoon
Published: January 2021

Most wind turbines are monitored and controlled by supervisory control and data acquisition systems that involve remote communication through networks. Despite the flexibility and efficiency that network-based monitoring and control systems bring, these systems are often threatened by cyberattacks. Among the various kinds of cyberattacks, some exploit the system dynamics so that the attack cannot be detected by monitoring system output, the zero-dynamics attack is one of them. This paper confirms that the zero-dynamics attack is fatal to wind turbines and the attack can cause system breakdown. In order to protect the system, we present two defense strategies using a generalized hold and a generalized sampler. These methods have the advantage that the zeros can be placed so that the zero dynamics of the system become stable; as a consequence, the zero-dynamics attack is neutralized. The effects of the countermeasures are validated through numerical simulations and the comparative discussion between two methods is provided.
Source Apportionment and Assessment of Air Quality Index of PM2.5–10 and PM2.5 in at Two Different Sites in Urban Background Area in Senegal
Authors: Kebe Moustapha , Traore Alassane , Manousakas Manousos Ioannis , Vasilatou Vasiliki , Ndao Ababacar Sadikhe , Wague Ahmadou , Eleftheriadis Konstantinos
Published: January 2021

Identifying the particulate matter (PM) sources is an essential step to assess PM effects on human health and understand PM’s behavior in a specific environment. Information about the composition of the organic or/and inorganic fraction of PM is usually used for source apportionment studies. In this study that took place in Dakar, Senegal, the identification of the sources of two PM fractions was performed by utilizing data on the elemental composition and elemental carbon content. Four PM sources were identified using positive matrix factorization (PMF): Industrial emissions, mineral dust, traffic emissions, and sea salt/secondary sulfates. To assess the effect of PM on human health the air quality index (AQI) was estimated. The highest values of AQI are approximately 497 and 488, in Yoff and Hlm, respectively. The spatial location of the sources was investigated using potential source contribution function (PSCF). PSCF plots revealed the high effect of transported dust from the desert regions to PM concentration in the sampling site. To the best of our knowledge, this is the first source apportionment study on PM fractions published for Dakar, Senegal.
Urban Ground-Level O3 Trends: Lessons from Portuguese Cities, 2010–2018
Authors: Soares Angelo Roldão , Deus Ricardo , Barroso Carla , Silva Carla
Published: January 2021

Big datasets of air-quality pollutants and weather data allow us to review trends of NO2, NO, O3, and global radiation (GR), for Lisbon, Porto and Coimbra, with regard to the historical period of 2010–2018. GR is expected to have a considerable impact on photochemical reactions of the O3 formation mechanism. We aim to characterize daily, monthly, and yearly trends. We explore Weekday (WD) versus weekend (WE), and seasonality of O3 and NO2. We are interested to know these pollutant peak concentration variations over the years and investigate if parallels can be drawn between urban mobility indicators and these pollutants. For this purpose, economic data, European emission standards, and car stock data (fuel, age, and number of vehicles) are cross-analyzed. How are they correlated? Has it impacted NO2 and O3 variations? How do different air-quality monitoring stations (AQMS), traffic and non-traffic, compare? How is Lisbon NOx-O3 correlated? What are its implications for future scenarios? Results show that urban mobility trends and economic events are correlated with NO2 and O3 variability. Weekend effect has a partial relationship with urban mobility trends and economy as it is relatively well correlated for Lisbon but not for Porto and Coimbra. Nonetheless, weekend effect for the period of 2010–2018 is overall trending upwards for all cities. In Lisbon and Coimbra, O3 concentrations also trend upwards during the same 2010–2018 period but for Porto they do not. Regardless, for the period of 2015–2018, after the economic recession, the upwards trends of both weekend effect and overall O3 concentrations are clear for all AQMS. For AQMS peak values comparison, Lisbon traffic AQMS registered an annual averaged 8-hour daily max O3 concentration of 34.4 ppb while Lisbon non-traffic AQMS presented 39.1 ppb. Altogether, annual 8-hour daily maximum values for 2010–2018 traffic AQMS in Lisbon show an inverse relationship with fuel sales, and have concentrations fluctuating between 28–35 ppb, which is slightly higher than the 2001–2010 historical European range of 27–31 ppb. Lastly, for the 8 years data in Lisbon, it has been shown that a negative NOx-O3 correlation exists, and the study location might be VOC–sensitive. This means that as NOx concentrations decrease, O3 concentrations become exponentially higher. Further research into VOCs with better data availability is required to make more concise claims. Regardless, it can be inferred that in a future scenario where mitigation continues to escalate, through O3 emission standards and an aggressive shift of car stock to electric vehicles, achieving unprecedented rises in O3 concentrations could be observed.
Lysosomal Function and Axon Guidance: Is There a Meaningful Liaison?
Authors: Manzoli Rosa , Badenetti Lorenzo , Rubin Michela , Moro Enrico
Published: January 2021

Axonal trajectories and neural circuit activities strongly rely on a complex system of molecular cues that finely orchestrate the patterning of neural commissures. Several of these axon guidance molecules undergo continuous recycling during brain development, according to incompletely understood intracellular mechanisms, that in part rely on endocytic and autophagic cascades. Based on their pivotal role in both pathways, lysosomes are emerging as a key hub in the sophisticated regulation of axonal guidance cue delivery, localization, and function. In this review, we will attempt to collect some of the most relevant research on the tight connection between lysosomal function and axon guidance regulation, providing some proof of concepts that may be helpful to understanding the relation between lysosomal storage disorders and neurodegenerative diseases.
Role of Kallikrein 7 in Body Weight and Fat Mass Regulation
Authors: Kunath Anne , Weiner Juliane , Krause Kerstin , Rehders Maren , Pejkovska Anastasija , Gericke Martin , Biniossek Martin L. , Dommel Sebastian , Kern Matthias , Ribas-Latre Aleix , Schilling Oliver , Brix Klaudia , Stumvoll Michael , Klöting Nora , Heiker John T. , Blüher Matthias
Published: January 2021

Increased plasma and adipose tissue protease activity is observed in patients with type 2 diabetes and obesity. It has been proposed that specific proteases contribute to the link between obesity, adipose tissue inflammation and metabolic diseases. We have recently shown that ablation of the serine protease kallikrein-related peptidase 7 (Klk7) specifically in adipose tissue preserves systemic insulin sensitivity and protects mice from obesity-related AT inflammation. Here, we investigated whether whole body Klk7 knockout (Klk7−/−) mice develop a phenotype distinct from that caused by reduced Klk7 expression in adipose tissue. Compared to littermate controls, Klk7−/− mice gain less body weight and fat mass both under chow and high fat diet (HFD) feeding, are hyper-responsive to exogenous insulin and exhibit preserved adipose tissue function due to adipocyte hyperplasia and lower inflammation. Klk7−/− mice exhibit increased adipose tissue thermogenesis, which is not related to altered thyroid function. These data strengthen our recently proposed role of Klk7 in the regulation of body weight, energy metabolism, and obesity-associated adipose tissue dysfunction. The protective effects of Klk7 deficiency in obesity are likely linked to a significant limitation of adipocyte hypertrophy. In conclusion, our data indicate potential application of specific KLK7 inhibitors to regulate KLK7 activity in the development of obesity and counteract obesity-associated inflammation and metabolic diseases.
Sociodemographic and Health-Related Factors Associated with Severity of Cognitive Impairment in Elderly Patients Hospital-ized in a Geriatric Clinic
Authors: Kłoszewska Marta , Łyszczarz Błażej , Kędziora-Kornatowska Kornelia
Published: January 2021

Identification of risk factors for cognitive impairment is crucial for providing proper care and treatment. The aim of the study was to investigate the relationship between sociodemographic and health-related factors and the severity of cognitive impairment in elderly patients. In this retrospective study, we assessed the medical documentation of 323 patients aged 60+ years hospitalized in a geriatric clinic of university hospital. The patients were classified into five groups of cognitive impairment severity based on the Mini Mental State Examination and Clock Drawing Test. Kruskal-Wallis and Chi square tests and multivariate ordinal logistic regression were used to assess relationships involved. Cognitive impairment was identified in 84.2% of subjects. The following factors were indicative for higher level of cognitive disorders: primary and vocational education, older age, presence of vascular brain injury, and inability of walking independently. On the other hand, the factors associated with lower severity of cognitive impairment were co-morbid anxiety disorders, ischemic heart disease, and a higher BMI index. Dementia is one of the leading causes of disability and mortality in the elderly. Enhancing knowledge about the risk factors that worsen cognition is particularly relevant for accelerating the diagnosis of dementia and improving patient care.
DNA Damage Response in Multiple Myeloma: The Role of the Tumor Microenvironment
Authors: Saitoh Takayuki , Oda Tsukasa
Published: January 2021

Multiple myeloma (MM) is an incurable plasma cell malignancy characterized by genomic instability. MM cells present various forms of genetic instability, including chromosomal instability, microsatellite instability, and base-pair alterations, as well as changes in chromosome number. The tumor microenvironment and an abnormal DNA repair function affect genetic instability in this disease. In addition, states of the tumor microenvironment itself, such as inflammation and hypoxia, influence the DNA damage response, which includes DNA repair mechanisms, cell cycle checkpoints, and apoptotic pathways. Unrepaired DNA damage in tumor cells has been shown to exacerbate genomic instability and aberrant features that enable MM progression and drug resistance. This review provides an overview of the DNA repair pathways, with a special focus on their function in MM, and discusses the role of the tumor microenvironment in governing DNA repair mechanisms.
Printing the Pathway Forward in Bone Metastatic Cancer Research: Applications of 3D Engineered Models and Bioprinted Scaffolds to Recapitulate the Bone–Tumor Niche
Authors: Hughes Anne M. , Kolb Alexus D. , Shupp Alison B. , Shine Kristy M. , Bussard Karen M.
Published: January 2021

Breast cancer commonly metastasizes to bone, resulting in osteolytic lesions and poor patient quality of life. The bone extracellular matrix (ECM) plays a critical role in cancer cell metastasis by means of the physical and biochemical cues it provides to support cellular crosstalk. Current two-dimensional in-vitro models lack the spatial and biochemical complexities of the native ECM and do not fully recapitulate crosstalk that occurs between the tumor and endogenous stromal cells. Engineered models such as bone-on-a-chip, extramedullary bone, and bioreactors are presently used to model cellular crosstalk and bone–tumor cell interactions, but fall short of providing a bone-biomimetic microenvironment. Three-dimensional bioprinting allows for the deposition of biocompatible materials and living cells in complex architectures, as well as provides a means to better replicate biological tissue niches in-vitro. In cancer research specifically, 3D constructs have been instrumental in seminal work modeling cancer cell dissemination to bone and bone–tumor cell crosstalk in the skeleton. Furthermore, the use of biocompatible materials, such as hydroxyapatite, allows for printing of bone-like microenvironments with the ability to be implanted and studied in in-vivo animal models. Moreover, the use of bioprinted models could drive the development of novel cancer therapies and drug delivery vehicles.
The Current View of Nonalcoholic Fatty Liver Disease-Related Hepatocellular Carcinoma
Authors: Kogiso Tomomi , Tokushige Katsutoshi
Published: January 2021

Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and can develop into hepatocellular carcinoma (HCC). The incidence of NAFLD-related HCC, which is accompanied by life-threatening complications, is increasing. Advanced fibrosis and lifestyle-related and metabolic comorbidities, especially obesity and diabetes mellitus, are associated with HCC development. However, HCC is also observed in the non-cirrhotic liver. Often, diagnosis is delayed until the tumor is relatively large and the disease is advanced; an effective screening or surveillance method is urgently required. Recently, the NAFLD/nonalcoholic steatohepatitis (NASH) guidelines of Japan were revised to incorporate new strategies and evidence for the management and surveillance of NAFLD/NASH. Fibrosis must be tested for noninvasively, and the risk of carcinogenesis must be stratified. The treatment of lifestyle-related diseases is expected to reduce the incidence of NAFLD and prevent liver carcinogenesis.
Circulating Cell-Free DNA Combined to Magnetic Resonance Imaging for Early Detection of HCC in Patients with Liver Cirrhosis
Authors: Alunni-Fabbroni Marianna , Weber Sabine , Öcal Osman , Seidensticker Max , Mayerle Julia , Malfertheiner Peter , Ricke Jens
Published: January 2021

Liquid biopsy based on circulating cell-free DNA (cfDNA) is a promising non-invasive tool for the prognosis of hepatocellular cancer (HCC). In this exploratory study we investigated whether cfDNA and gene variants associated with HCC may be found in patients with liver cirrhosis (LC) and thus identify those at an increased risk for HCC. A cohort of 40 LC patients with no suspect neoplastic lesions was included in this study. Next generation sequencing (NGS) of cfDNA isolated from plasma was performed on a panel of 597 selected genes. Images of the patients who underwent MRI with hepatospecific contrast media during the study period were retrospectively re-evaluated (imaging was not part of the prospective study). cfDNA was detected in the plasma of 36 patients with LC. NGS-based analyses identified 20 variants in different combinations. Re-evaluation of the MRI images that were available for a proportion of the patients (n = 27) confirmed the absence of lesions in 8 cases carrying cfDNA without variants. In 6 of 19 patients with identified variants and MRI images available, MRI revealed a precursor lesion compatible with HCC and new lesions were discovered at follow-up in two patients. These precursor lesions were amenable for curative treatments. Mutation analysis revealed selective HCC related gene mutations in a subset of patients with LC, raising the suspect that these patients were at an increased risk for HCC development. MRI findings confirmed suspect nodular lesions of early stage HCC not detected with current standard screening procedures, which were only seen in patients carrying cfDNA variants. This opens a perspective for an HCC screening strategy combining both liquid biopsy and MRI in patients with LC.
Human Chorionic Gonadotropin-Mediated Induction of Breast Cancer Cell Proliferation and Differentiation
Authors: Dando Ilaria , Carmona-Carmona Cristian Andres , Zampieri Nicola
Published: January 2021

Human chorionic gonadotropin (hCG) is a hormone that specifically binds to luteinizing hormone receptor (LHR) and exerts several roles, including the support of pregnancy and fetal gonadal steroidogenesis. Since hCG is also expressed by some tumor types, like breast cancer, many efforts have been made to study its role in neoplesia, with some studies showing a cancer-supportive role and others showing a cancer-protective role. A critical examination of the literature highlighted that the in vitro effect of hCG has been tested in the presence of fetal serum, which contains other gonadotropins, in the culture medium. Thus, we hypothesized that the use of serum in the cell culture medium might influence the cell response to the hCG treatment due to the presence of other hormones. Thus, we analyzed the in vitro effect of highly purified hCG on cell proliferation and the activation of the down-stream signal transduction pathway in three breast cancer cell lines, particularly focusing on MCF7, cultured in serum-deprived conditions. Our data show that hCG increases cell proliferation and activates the down-stream target Akt, together with a decrease of the LHR mRNA expression level. Finally, we also tested the differentiation capacity of hCG on MCF7 cancer stem cells (CSCs) and show that it favors the proliferation and differentiation of these cells, thus suggesting that hCG also renders cells more able to colonize and invade the organs.